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1.
PLoS Biol ; 21(11): e3002379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37944100

RESUMO

[This corrects the article DOI: 10.1371/journal.pbio.3000324.].

2.
Compr Psychiatry ; 134: 152517, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39018815

RESUMO

BACKGROUND: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. METHODS: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. RESULTS: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. CONCLUSIONS: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.


Assuntos
Transtorno de Adição à Internet , Humanos , Adolescente , Masculino , Transtorno de Adição à Internet/psicologia , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/diagnóstico , Feminino , China , Estudos Transversais , Reprodutibilidade dos Testes , Inquéritos e Questionários/normas , Psicometria/instrumentação , Psicometria/normas , Internet , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/psicologia , Mídias Sociais/estatística & dados numéricos , Jogos de Vídeo/psicologia , Comportamento do Adolescente/psicologia , Escalas de Graduação Psiquiátrica/normas , População do Leste Asiático
3.
Public Health ; 236: 373-380, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303625

RESUMO

OBJECTIVES: The objectives of the present study were to (i) re-evaluate and expand the psychometric properties of two weight stigma instruments-the Perceived Weight Stigma Scale (PWSS) and the Weight Self-Stigma Questionnaire (WSSQ) among a large sample of adolescents using advanced psychometric methods and (ii) examine how the different types of weight stigma (i.e., PWSS and WSSQ) are associated with psychological distress. STUDY DESIGN: Cross-sectional study. METHODS: In September 2023, a cross-sectional survey utilising convenience sampling was used to recruit 9995 adolescents (mean age = 16.36 years [standard deviation = 0.78]; 57.8% males). They completed the PWSS, WSSQ, and a measure on psychological distress. The data were analysed using Rasch analysis, confirmatory factor analysis (CFA), structural equation modelling (SEM), and network analysis. RESULTS: The CFA and Rasch model results showed acceptable psychometric properties regarding factor structure, factor loading, difficulty, and infit and outfit mean squares (except Items 4 and 7 of the PWSS). There was no substantial differential item functioning for any tested items across the sex and weight categories. The CFA and SEM results showed promising validity indices with significant associations between both weight stigma scales and psychological distress (i.e., depression, anxiety, and stress). Network analysis showed inter-variable connectivity between nodes PWSS3 ("People act as if they are afraid of you") and WSSQF7 ("I feel insecure about others' opinions of me"). CONCLUSIONS: Both weight stigma scales had acceptable psychometric properties and were significantly associated with psychological distress, although each assessed different types of weight stigma. This suggests that researchers and clinicians can use these scales to reliably and validly assess weight stigmas among adolescents.

4.
PLoS Biol ; 17(6): e3000324, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31226106

RESUMO

The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2-cell (2C)-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2C-stage embryos. By studying the transition of ESCs into 2C-like cells, we identified developmental pluripotency associated 2 and 4 (Dppa2/4) as important regulators controlling zygotic transcriptional program through directly up-regulating the expression of double homeobox (Dux). In addition, we found that DPPA2 protein is sumoylated and its activity is negatively regulated by small ubiquitin-like modifier (Sumo) E3 ligase protein inhibitor of activated STAT 4 (PIAS4). PIAS4 is down-regulated during ZGA process and during transitioning of ESCs into 2C-like cells. Depleting Pias4 or overexpressing Dppa2/4 is sufficient to activate 2C-like transcriptional program, whereas depleting Dppa2/4 or forced expression of Pias4 or Sumo2-Dppa2 inhibits 2C-like transcriptional program. Furthermore, ectopic expression of Pias4 or Sumo2-Dppa2 impairs early mouse embryo development. In summary, our study identifies key molecular rivals consisting of transcription factors and a Sumo2 E3 ligase that regulate zygotic transcriptional program upstream of Dux.


Assuntos
Proteínas Nucleares/metabolismo , Proteínas Inibidoras de STAT Ativados/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Desenvolvimento Embrionário/genética , Células-Tronco Embrionárias/metabolismo , Feminino , Genoma , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/fisiologia , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas Inibidoras de STAT Ativados/fisiologia , Proteína SUMO-1/metabolismo , Proteína SUMO-1/fisiologia , Análise de Célula Única , Sumoilação , Fatores de Transcrição/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Zigoto/metabolismo
5.
Stereotact Funct Neurosurg ; 93(6): 407-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26731566

RESUMO

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.


Assuntos
Fissura , Procedimentos Neurocirúrgicos/métodos , Núcleo Accumbens/cirurgia , Transtornos Relacionados ao Uso de Opioides/cirurgia , Adulto , Feminino , Humanos , Masculino , Estado Nutricional , Transtornos Relacionados ao Uso de Opioides/psicologia , Período Pós-Operatório , Resultado do Tratamento
6.
Int J Neurosci ; 125(5): 380-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24985045

RESUMO

PURPOSE: Non-human primate models of deep brain stimulation (DBS) play an increasingly important role in the exploration of DBS mechanisms. The establishment and recognized usefulness of such models depend on the precise positioning of the stimulating targets and electrode implants. The optimal method of targeting remains controversial. MATERIALS AND METHODS: This paper described an improved stereotactic procedure that uses a self-developed adaptor to improve accuracy. This involved: (1) connecting clinical stereotactic devices with the skull of primates using a self-developed adaptor; (2) pre-operation targeting via magnetic resonance imaging (MRI); (3) target re-checking by microelectrode recording (MER); (4) DBS electrode implantation; (5) post-operative MRI verification of electrode placement and (6) positioning confirmation by DBS programming. RESULTS: Use of the adaptor enabled clinical stereotactic surgery, pre-operative MRI targeting, microelectrode mapping and post-operative verification in primate DBS operations. Discrepancies between achieved and predetermined electrode position were around 0.6 mm. DBS programming improved the motor function of the hemiparkinsonism animals and decreased the numbers of rotation induced by apomorphine, indicating the precise positioning of the stimulating target and successful implanting of electrode using this method. CONCLUSIONS: An improved stereotactic procedure was performed during a non-human primate DBS operation using a self-developed adaptor. The accuracy of DBS electrode implantation in non-human primates was improved with this method.


Assuntos
Estimulação Encefálica Profunda/métodos , Eletrodos Implantados , Técnicas Estereotáxicas , Núcleo Subtalâmico/fisiologia , Animais , Estimulação Encefálica Profunda/instrumentação , Modelos Animais de Doenças , Potencial Evocado Motor/fisiologia , Lateralidade Funcional/fisiologia , Imageamento Tridimensional , Intoxicação por MPTP/terapia , Macaca , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologia , Núcleo Subtalâmico/anatomia & histologia
7.
Mol Biomed ; 5(1): 46, 2024 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388072

RESUMO

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.


Assuntos
Lesões por Radiação , Transdução de Sinais , Células-Tronco , Humanos , Células-Tronco/efeitos da radiação , Células-Tronco/metabolismo , Animais , Lesões por Radiação/terapia , Lesões por Radiação/patologia , Transdução de Sinais/efeitos da radiação , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Enteropatias/patologia , Intestinos/efeitos da radiação , Intestinos/patologia
8.
Heliyon ; 10(2): e24391, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312537

RESUMO

Background: In recent years, most studies believe that high TSH level is positively correlated with the incidence of thyroid cancer, but it is still controversial. For this reason, the purpose of this study is to analyze the correlation between preoperative TSH level and thyroid malignant nodules using pathological diagnosis as the gold standard. To evaluate the role of serum TSH in predicting malignancy of thyroid nodules with uncertain cytology.As an important member of the hypothalamus-pituitary-thyroid axis in the endocrine system, TSH plays a crucial role in regulating the growth, differentiation, and function of thyroid cells (Zhang et al., 2023) [1]. Therefore, it has always been considered closely related to TC. Currently, most studies have compared the TSH levels of TC patients and individuals with benign thyroid disease or healthy controls. These findings from various studies indicated that TC patients often demonstrate elevated TSH levels, even when their TSH falls within the normal range. However, it is important to highlight that the current evidence primarily relies on cross-sectional studies, which mainly describe a phenomenon without establishing causal relationships. The involvement of TSH in the early onset or late progression of TC remains unknown, the interaction between TSH and other factors and how it affects TC is not well understood (Gubbi et al., 2020) [2].Symptoms of thyroid cancer are usually insidious, and early thyroid cancer often has no obvious clinical symptoms. Therefore, early detection and early treatment are particularly important, and how to improve the preoperative diagnosis rate of thyroid nodules is also a problem that clinicians pay close attention to. Objective: To evaluate the value of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma in patients with thyroid nodules. Methods: Our study searched databases in both Chinese and English.China Academic Journals FULL-text Database (CNKI), China Online Journals, Chinese Scientific Journals database and Chinese Biomedical Literature Database (CBM) were searched by computer. The English literature was established by PubMed, Embase, Cochrane Library, Web of Science and other databases until June 2022 to search for relevant literatures on the diagnostic test of serum TSH concentration in patients with thyroid nodule. The literatures that met the criteria were screened, the data were extracted, and the literature quality was evaluated. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the method for the diagnosis of differentiated thyroid carcinoma were calculated and summarized. The receiver operating characteristic (SROC) curve was drawn and the area under the curve was obtained. Results: A total of 23 diagnostic tests were included (5348 lesions). Meta-analysis showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma were 0.64, 0.72, 2.511, 0.386 and 7.14, respectively. The area under SROC curve (AUC) was 0.79, and the Q index was 0.7283, indicating no statistically significant difference. Conclusion: Based on current evidence, detection of serum TSH concentration in thyroid nodule patients has high sensitivity and specificity for the diagnosis of differentiated thyroid cancer, which has good clinical application value. However, other auxiliary examinations are still needed to improve the diagnosis rate.

9.
Clin Transl Oncol ; 26(6): 1338-1347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38097822

RESUMO

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.


Assuntos
Carcinoma Adenoide Cístico , Humanos , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , China/epidemiologia , Estudos de Casos e Controles , Adulto , Idoso , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Gradação de Tumores , Transformação Celular Neoplásica/patologia , Metástase Linfática , Taxa de Sobrevida , Invasividade Neoplásica , Adulto Jovem
10.
Transl Neurodegener ; 13(1): 8, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317265

RESUMO

BACKGROUND: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. METHODS: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. RESULTS: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). CONCLUSIONS: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.


Assuntos
COVID-19 , Doença de Parkinson , Humanos , COVID-19/epidemiologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Pandemias , Estudos Transversais , Controle de Doenças Transmissíveis , Inquéritos e Questionários , China/epidemiologia
12.
World J Pediatr ; 19(2): 158-169, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36409452

RESUMO

BACKGROUND: The neonatal period is the most vulnerable period during childhood, with the risk of death being the highest even in developed countries/regions. Hong Kong's neonatal mortality (1‰) is among the world's lowest and has remained similar for 15 years. This study aimed to explore neonatal deaths in Hong Kong in detail and determine whether neonatal mortality is reducible at such a low level. METHODS: Live births in public hospitals in Hong Kong during 01 Jan 2006-31 Dec 2017 were included. Relevant data were extracted from the electronic medical records. Gestational age-specific mortality was calculated, and the trends were analyzed using the Cochran-Armitage trend test. Causes of death were summarized, and risk factors were identified in multivariate logistic regression analysis. RESULTS: In 490,034 live births, 755 cases (1.54‰) died during the neonatal period, and 293 (0.6‰) died during the post-neonatal period. The neonatal mortality remained similar overall (P = 0.17) and among infants born at 24-29 weeks' gestation (P = 0.4), while it decreased in those born at 23 (P = 0.04), 30-36 (P < 0.001) and ≥ 37 (P < 0.001) weeks' gestation. Neonates born at < 27 weeks' gestation accounted for a significantly increased proportion among cases who died (27.6% to 51.9%), with hemorrhagic conditions (24%) being the leading cause of death. Congenital anomalies were the leading cause of death in neonates born ≥ 27 weeks' gestation (52%), but its cause-specific mortality decreased (P = 0.002, 0.6‰ to 0.41‰), with most of the decrease attributed to trisomy 13/18 and multiple anomalies. CONCLUSION: Reduction of neonatal mortality in developed regions may heavily rely on improved quality of perinatal and neonatal care among extremely preterm infants.


Assuntos
Mortalidade Infantil , Recém-Nascido Prematuro , Lactente , Gravidez , Feminino , Recém-Nascido , Humanos , Hong Kong/epidemiologia , Estudos Retrospectivos , Idade Gestacional
13.
Am J Transl Res ; 15(11): 6626-6631, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074820

RESUMO

De novo glomerular injuries or relapse of nephropathy following COVID-19 vaccine has been reported. Here we present the first case of successful treatment of new-onset diabetes mellitus and biopsy-proven IgA nephropathy after COVID-19 vaccination. A 56-year-old man with no known medical history of renal dysfunction or diabetes mellitus developed both within 3 months after receiving a third dose of inactivated COVID-19 vaccine (Vero cells). His symptoms were characterized by brown urine, severe dry mouth, and excessive thirst. Randomly acquired blood glucose levels exceeded 33.3 mmol/L. A kidney biopsy showed IgA nephropathy. He was started on insulin for glycemic control. After glucocorticoid and cyclophosphamide treatment, oral tablets of repaglinide, combined with acarbose, controlled blood glucose and stabilized kidney function. This case is unique because the kidneys and pancreas were simultaneously affected by the vaccine. Successful treatment of the disease proved that cyclophosphamide combined with glucocorticoids were effective and that blood glucose was successfully controlled. This treatment option could be useful in similar cases in the future.

14.
Ageing Res Rev ; 91: 102077, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37742785

RESUMO

Parkinson's Disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN), leading to motor and non-motor symptoms. While the exact mechanisms remain complex and multifaceted, several molecular pathways have been implicated in PD pathology, including accumulation of misfolded proteins, impaired mitochondrial function, oxidative stress, inflammation, elevated iron levels, etc. Overall, PD's molecular mechanisms involve a complex interplay between genetic, environmental, and cellular factors that disrupt cellular homeostasis, and ultimately lead to the degeneration of dopaminergic neurons. Recently, emerging evidence highlights ferroptosis, an iron-dependent non-apoptotic cell death process, as a pivotal player in the advancement of PD. Notably, oligomeric α-synuclein (α-syn) generates reactive oxygen species (ROS) and lipid peroxides within cellular membranes, potentially triggering ferroptosis. The loss of dopamine, a hallmark of PD, could predispose neurons to ferroptotic vulnerability. This unique form of cell demise unveils fresh insights into PD pathogenesis, necessitating an exploration of the molecular intricacies connecting ferroptosis and PD progression. In this review, the molecular and regulatory mechanisms of ferroptosis and their connection with the pathological processes of PD have been systematically summarized. Furthermore, the features of ferroptosis in PD animal models and clinical trials targeting ferroptosis as a therapeutic approach in PD patients' management are scrutinized.


Assuntos
Ferroptose , Doença de Parkinson , Animais , Humanos , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Substância Negra/metabolismo , Estresse Oxidativo , Ferro/metabolismo , Neurônios Dopaminérgicos/metabolismo
15.
Exp Mol Med ; 55(3): 597-611, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36879115

RESUMO

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Tretinoína/farmacologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Neoplasias Pulmonares/genética , Transdução de Sinais , Receptor Notch1/genética
16.
Acta Pharmacol Sin ; 33(5): 588-93, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504903

RESUMO

AIM: It has been reported that nucleus accumbens (NAc) lesions can help to prevent relapse in opioid addicts. This article aimed to investigate associations between personality changes and NAc lesions. METHODS: The surgery group consisted of 78 patients who had received bilateral stereotactic lesions of the NAc to treat opioid addiction. Seventy two non-surgery opioid addicts were appropriately paired with the patients of the surgery group as the non-surgery group. All participants were interviewed in person and received urine tests, naloxone provocative tests and hair tests to determine the prevalence of relapse. Eysenck personality questionnaire (EPQ) and the health survey questionnaire (SF-36) were employed to assess personality and functional health, respectively. RESULTS: In the surgery group, 30 participants relapsed, and the non-relapse rate was 61.5% (48/78). Compared with the Chinese normative data, the neuroticism (N) and psychoticism (P) dimensions of the EPQ in the non-surgery group were significantly higher, whereas the lie (L) dimension was significantly lower. There was no significant difference in all dimensions of the EPQ between the surgery group and the Chinese normative data. The N dimension in the relapse group and the L dimension in the surgery group were significantly lower than those of the non-surgery group. The P dimension in the relapse group was significantly higher than that of the non-relapse group. The extraversion (E) dimension was relatively stable between these groups. CONCLUSION: Although the influence of other factors cannot be excluded, it is apparent that surgically induced NAc lesions are associated with lower P and N dimensions for opioid addicts, and a higher P dimension is associated with a tendency to relapse.


Assuntos
Comportamento Aditivo/cirurgia , Usuários de Drogas/psicologia , Núcleo Accumbens/cirurgia , Transtornos Relacionados ao Uso de Opioides/cirurgia , Personalidade , Técnicas Estereotáxicas , Adolescente , Adulto , Comportamento Aditivo/psicologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/patologia , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/psicologia , Recidiva , Detecção do Abuso de Substâncias , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Sci Rep ; 12(1): 11711, 2022 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810209

RESUMO

The self-administration (SA) model represents one of the most important and classic methods for drug addiction, and jugular vein catheterization is one of the most critical techniques in this animal model. We aimed to explore an optimized scheme to improve the success rate of rat jugular vein catheterization and SA model. Our experiment provided an optimized scheme which including numerous details, materials, approaches, updated techniques and protocols. Our experimental group consisted of 120 adult male Sprague-Dawley rats, which were divided into the Traditional Operation group (TO group) and the Optimized Operation group (OO group) by the random number table method and then further individually divided into the Saline Training group and the Cocaine Training group for the following SA training. Our results showed that the success rate of the jugular vein catheterization in the OO group was significantly greater than that in the TO group (93.33% vs 46.67%, χ2 = 31.11, P < 0.001). The optimized jugular vein catheterization could make the SA model more stable, reliable and efficient than the traditional operation. Compared with traditional methods, our optimized scheme made numerous improvements in materials and techniques including uniformity, individualized variability of the S-type positioning nail, the length and connection matching, the shape of the end and low cost. Our optimized scheme could provide a more stable and efficient tool for basic research on drug addiction. Several subtle improvements under our personal experience are usually important for augmenting operational efficiency.


Assuntos
Cateterismo Venoso Central , Transtornos Relacionados ao Uso de Cocaína , Cocaína , Animais , Cateterismo Venoso Central/métodos , Veias Jugulares , Masculino , Ratos , Ratos Sprague-Dawley
18.
World J Clin Cases ; 10(12): 3773-3786, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35647160

RESUMO

BACKGROUND: Evaluation of the effectiveness of melatonin is necessary to prevent the development of delirium in hospitalized patients. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland of the brain from the amino acid tryptophan. Synthetic melatonin supplements have been used for various medical conditions, especially sleep-related diseases, and have proved to be successful. AIM: To determine the effect of melatonin on the prevention of delirium in hospitalized patients. METHODS: A literature search of the CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, Web of Science, and other databases was conducted. The CNKI, Wanfang Database, VIP Database (VIP), and China Biomedical Literature Database were searched for Chinese studies, and PubMed, Embase, Cochrane Library, Web of Science and other databases were searched for international studies. It will be established in June 2021 in a randomized controlled trial (RCT) whether melatonin treatment for 6 mo prevents delirium in hospitalized patients. Literature screening, quality review, and data extraction were carried out using the Cochrane Manual 5.1.0 systematic evaluation method, and Stata 15.0 software and Review Manager 5.3 were used for meta-analysis and processing. RESULTS: A total of 18 new RCT articles and 18 experimental subjects were identified. The results of the meta-analysis showed that following the occurrence of delirium, melatonin reduced the incidence of delirium in patients (RR = 0.69, 95%CI: 0.60-0.80), which is of significance, but heterogeneity was significant I 2 = 62%. Subgroup analysis was performed to examine the source of heterogeneity, and it was found that different patient types were the source of heterogeneity; the research on subgroup analysis was of high quality and homogeneous. To determine the reliability and robustness of the research results, a sensitivity analysis was carried out. The results showed that after excluding individual studies one by one, the effect size was still within 95%CI, which strengthened the reliability of the original meta-analysis results. Melatonin has a significant preventive effect on delirium in hospitalized medical patients [RR = 0.60, 95%CI: 0.47-0.76), P < 0.001]. CONCLUSION: Melatonin can reduce the rate of delirium in medical patients, and the role of melatonin in reducing the incidence of delirium in surgical patients and critical care unit patients requires further study.

19.
Front Neurol ; 13: 1006227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330427

RESUMO

Objectives: Traumatic intracerebellar hematoma (TICH) is a very rare entity with a high morbidity and mortality rate, and there is no consensus on its optimal surgical management. In particular, whether and when to place external ventricle drainage in TICH patients without acute hydrocephalus pre-operation is still controversial. Methods: A single-institutional, retrospective analysis of total of 47 TICH patients with craniectomy hematoma evacuation in a tertiary medical center from January 2009 to October 2020 was performed. Primary outcomes were mortality in hospital and neurological function evaluated by GOS at discharge and 6 months after the ictus. Special attention was paid to the significance of external ventricular drainage (EVD) in TICH patients without acute hydrocephalus on admission. Results: Analysis of the clinical characteristics of the TICH patients revealed that the odds of use of EVD were seen in patients with IVH, fourth ventricle compression, and acute hydrocephalus. Placement of EVD at the bedside can significantly improve the GCS score before craniotomy, as well as the neurological score at discharge and 6 months. Compared with the only hematoma evacuation (HE) group, there is a trend that EVD can reduce hospital mortality and decrease the occurrence of delayed hydrocephalus, although the difference is not statistically significant. In addition, EVD can reduce the average NICU stay time, but has no effect on the total length of stay. Moreover, our data showed that EVD did not increase the risk of associated bleeding and intracranial infection. Interestingly, in terms of neurological function at discharge and 6 month after the ictus, even though without acute hydrocephalus on admission, the TICH patients can still benefit from EVD insertion. Conclusion: For TICH patients, perioperative EVD is safe and can significantly improve neurological prognosis. Especially for patients whose GCS dropped by more than 2 points before the operation, EVD can significantly improve the patient's GCS score, reduce the risk of herniation, and gain more time for surgical preparation. Even for TICH patients without acute hydrocephalus on admission CT scan, EVD placement still has positive clinical significance.

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