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1.
Int J Ophthalmol ; 17(6): 1007-1017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895685

RESUMO

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

2.
Mol Cancer ; 23(1): 113, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38802795

RESUMO

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinoma Hepatocelular , Proliferação de Células , Ferroptose , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , Proteínas de Neoplasias , RNA Circular , Animais , Feminino , Humanos , Masculino , Camundongos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Ferroptose/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Circular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Gen Hosp Psychiatry ; 87: 68-76, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38325144

RESUMO

OBJECTIVE: To identify the core residual symptom of MDD and assess its relationship with patients' long-term outcomes. METHOD: All patients were administered antidepressants during the acute phase and treated continuously. The 521 patients remitted at month 6 of a multicenter prospective project were included. Remission was defined as a Quick Inventory of Depressive Symptoms-Self-Report total score of ≤5. Functional impairments were measured with the Sheehan Disability Scale, quality of life with the Quality of Life Enjoyment and Satisfaction Questionnaire - short form, and family burden with the Family Burden Scale of Disease. Visits were scheduled at baseline, weeks 2, 8, 12, and month 6. RESULTS: Difficulty with concentration/decision making was the core residual symptom of MDD, determined with the centrality measure of network analysis. It was positively associated with functional impairments and family burden (r = 0.35, P < 0.01 and r = 0.31, P < 0.01, respectively) and negatively associated with life satisfaction (r = -0.29, P < 0.01). The exhibition of this residual symptom was associated with a family history of psychiatric disorders (OR = 2.610 [1.242-5.485]). CONCLUSIONS: The core residual symptom of MDD, difficulty with concentration/decision making, is associated with poorer social functioning, heavier family burden, and lower life satisfaction. Early detection and intervention of this symptom may be beneficial. CLINICAL TRIALS REGISTRATION NUMBER: (Chinese Clinical Trials.gov identifier) ChiCTR-OOC-17012566 and ChiCTR-INR-17012574.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Qualidade de Vida/psicologia , Estudos Prospectivos , Antidepressivos/uso terapêutico , Autorrelato
5.
J Laryngol Otol ; 138(5): 540-547, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348656

RESUMO

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.


Assuntos
Excisão de Linfonodo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Excisão de Linfonodo/métodos , Masculino , Neoplasias Nasofaríngeas/cirurgia , Neoplasias Nasofaríngeas/patologia , Carcinoma Nasofaríngeo/cirurgia , Carcinoma Nasofaríngeo/patologia , Feminino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Cadáver , Adulto , Faringe/cirurgia , Idoso , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento
6.
J Environ Radioact ; 273: 107393, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354571

RESUMO

In this paper, the influence of an earthquake on radon exhalation rate of uranium tailings reservoir beach under high temperature environment is studied by using a self-made integrated simulation test device for natural disasters, and a scale model test based on similarity and dimensional laws. The results show that, (1)When the peak acceleration reaches 0.6g, the radon exhalation rate increases sharply with the increase of peak acceleration, and tends to be gentle after 1.0g. (2)Under the action of high temperature, the radon exhalation rate increases rapidly with the increase of high temperature time, and gradually becomes flat after the 4th hour. (3)Compared with loading the earthquake condition only, the coupling effect of high temperatures and earthquakes causes a greater degree of damage to the beach surface of a uranium tailings reservoir under the same acceleration conditions, and the fissure rate and radon exhalation rate of the beach surface are substantially increased.


Assuntos
Terremotos , Monitoramento de Radiação , Radônio , Urânio , Radônio/análise , Temperatura , Urânio/análise , Expiração , Monitoramento de Radiação/métodos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38183633

RESUMO

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.

8.
Mol Med Rep ; 29(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38275129

RESUMO

Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS­CoV­2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS­CoV­2 N protein­induced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). The expression levels of SARS­CoV­2 N protein, SREBP cleavage­activating protein (SCAP), mature N­terminal SREBP2, NLRP3, procaspase­1, cleaved caspase­1, IL­1ß and IL­18 were examined by western blotting. The expression levels of SREBP2, HMG­CoA reductase, HMGCS1, low density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), SREBP1c, fatty acid synthase, stearyl coenzyme A desaturase 1, acetyl­CoA carboxylase α and ATP­citrate lyase were determined by reverse transcription­quantitative PCR. The translocation of SCAP or NLRP3 from the endoplasmic reticulum to the Golgi was detected by confocal microscopy. The results showed that excess PI promoted SCAP­SREBP and NLRP3 complex translocation to the Golgi, potentially leading to NLRP3 inflammasome activation and lipogenic gene expression. Furthermore, PI amplified SARS­CoV­2 N protein­induced inflammation via the SCAP­SREBP pathway, which facilitates NLRP3 inflammasome assembly and activation. Inhibition of phosphate uptake with phosphonoformate sodium alleviated NLRP3 inflammasome activation and reduced SREBP­mediated lipogenic gene expression in VSMCs stimulated with PI and with SARS­CoV­2 N protein overexpression. Inhibition of SREBP2 or small interfering RNA­induced silencing of SREBP2 effectively suppressed the effect of PI and SARS­CoV­2 N protein on NLRP3 inflammasome activation and lipogenic gene expression. In conclusion, the present study identified that PI amplified SARS­CoV­2 N protein­induced NLRP3 inflammasome activation and lipogenic gene expression via the SCAP­SREBP signaling pathway.


Assuntos
COVID-19 , Hiperfosfatemia , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pró-Proteína Convertase 9/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , SARS-CoV-2/metabolismo , Fosfatos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Transdução de Sinais , Inflamação
9.
J Affect Disord ; 347: 576-583, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38065479

RESUMO

BACKGROUND: There is not yet a valid and evidence-based system to classify patients with MDD into more homogeneous subtypes based on their clinical features. This study aims to identify symptom-based subtypes of MDD and investigate whether the treatment outcomes of those subtypes would be different. METHOD: The cohort was established at 12 densely populated cities of China. A total of 1487 patients were enrolled. All participants were 18-65 years old and diagnosed with MDD. Participants were followed up at baseline, weeks 4, 8, and 12, and months 4 and 6. K-means algorithm was used to cluster patients with MDD according to clinical symptoms. The network analysis was adopted to characterize and compare the symptom patterns in the clusters. We also examined the associations between the clusters and the clinical outcomes. RESULTS: The optimal number of the clusters was determined to be 2. Each cluster's maximum Jaccard Co-efficient was calculated to be >0.5 (cluster1 = 0.53, cluster 2 = 0.67). The symptom "depressed mood" and some other affective symptoms were the most prominent in cluster 1. Somatic symptoms, such as weight loss and general somatic symptoms, had the greatest expected influence in cluster 2. Compared with the response rates of the patients in the "somatic cluster", those of the patients in the "affective cluster" were significantly higher (P < 0.05). CONCLUSIONS: Patients with MDD might be classified into two symptom-based subtypes featured with affective symptoms or somatic symptoms. The treatment efficacy and prognosis of the subtype featured with somatic symptoms may be worse.


Assuntos
Transtorno Depressivo Maior , Sintomas Inexplicáveis , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/terapia , Estudos Prospectivos , Resultado do Tratamento , China/epidemiologia , Análise por Conglomerados
10.
J Ethnopharmacol ; 321: 117492, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38012974

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS, or Happy Feeling Powder), a typical Chinese herbal prescription, is frequently used for treating depression by the multi-level and multi-target mechanism. AIM OF THE STUDY: To systematically investigate the efficacy and safety of KXS on depression in preclinic trials. MATERIALS AND METHODS: We independently searched for preclinical animal studies of KXS on depression from inception to June 28, 2022, using electronic databases, e.g., PUBMED. The measurements were performed to assess the outcomes of behavioral tests. RESULTS: This systematic review and meta-analysis included twenty-four studies and 608 animals. A remarkable effect of KXS in depression behavioral tests, including sucrose consumption test (SMD: 2.36, 95% CI: (1.81, 2.90); Z = 8.49, P < 0.00001)., forced swimming test (MD = -60.52, 95% CI: (-89.04, -31.99); Z = 4.16, P < 0.0001), rearing times (MD=4.48, 95% CI: (3.39, 5.57); Z = 8.05, P < 0.00001) and crossing times (MD = -33.7, 95% CI: (25.74, 41.67); Z = 8.29, P < 0.00001) in the open field test, showing KXS's excellent efficiency in improving depressive-like symptoms of animals. CONCLUSIONS: Our meta-analysis showed KXS remarkably relieved animals' depressive-like symptoms, providing evidence that KXS can be a promising drug candidate for depression treatment.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Animais , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Roedores , Modelos Animais de Doenças
11.
Tissue Cell ; 86: 102276, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37979395

RESUMO

The sterol regulatory element-binding protein (SREBP) activation and cytokine level were significantly increased in coronavirus disease-19. The NLRP3 inflammasome is an amplifier for cellular inflammation. This study aimed to elucidate the modulatory effect of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP) on trimethylamine N-oxide (TMAO)-induced lipogenesis and NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). Our data indicated that SARS-CoV-2 NP activates the dissociation of the SREBP cleavage activating protein (SCAP) from the endoplasmic reticulum, resulting in SREBP activation, increased lipogenic gene expression, and NLRP3 inflammasome activation. TMAO was applied to VSMC-induced NLRP3 inflammasome by promoting the SCAP-SREBP complex endoplasmic reticulum-to-Golgi translocation, which facilitates directly binding of SARS-CoV-2 NP to the NLRP3 protein for NLRP3 inflammasome assembly. SARS-CoV-2 NP amplified the TMAO-induced lipogenic gene expression and NLRP3 inflammasome. Knockdown of SCAP-SREBP2 can effectively reduce lipogenic gene expression and alleviate NLRP3 inflammasome-mediated systemic inflammation in VSMCs stimulated with TMAO and SARS-CoV-2 NP. These results reveal that SARS-CoV-2 NP amplified TMAO-induced lipogenesis and NLRP3 inflammasome activation via priming the SCAP-SREBP signaling pathway.


Assuntos
COVID-19 , Metilaminas , Proteínas de Ligação a Elemento Regulador de Esterol , Humanos , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , SARS-CoV-2 , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Transdução de Sinais , Inflamação , Proteínas do Nucleocapsídeo
12.
Eur J Clin Pharmacol ; 80(2): 287-296, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38117332

RESUMO

PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI). METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes. RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups. CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.


Assuntos
Ketamina , Humanos , Ketamina/efeitos adversos , Ideação Suicida , Depressão , Administração Intranasal , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Int. j. clin. health psychol. (Internet) ; 23(4)oct.-dic. 2023. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-226359

RESUMO

Background/objective: Patients with major depressive disorder (MDD) have altered learning rates for rewards and losses in non-social learning paradigms. However, it is not well understood whether the ability to learn from social interactions is altered in MDD patients. Using reinforcement learning during the repeated Trust Game (rTG), we investigated how MDD patients learn to trust newly-met partners in MDD patients. Method: Sixty-eight MDD patients and fifty-four controls each played as ‘investor’ and interacted with ten different partners. We manipulated both the level of trustworthiness by varying the chance of reciprocity (10, 30, 50, 70 and 90%) and reputation disclosure, where partners’ reputation was either pre-disclosed or hidden. Results: Our reinforcement learning model revealed that MDD patients had significantly higher learning rates for losses than the controls in both the reputation disclosure and non-disclosure condition. The difference was larger when reputation was not disclosed than disclosed. We observed no difference in learning rates for gains in either condition. Conclusions: Our findings highlight that abnormal learning for losses underlies the social learning process in MDD patients. This abnormality is higher when situational unpredictability is high versus low. Our findings provide novel insights into social rehabilitation of MDD. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Transtorno Depressivo Maior , Aprendizado Social , Confiança , Relações Interpessoais , Reforço Psicológico
14.
Technol Cancer Res Treat ; 22: 15330338231212073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920989

RESUMO

Background: Endoplasmic reticulum (ER) stress plays a pro-apoptotic role in colorectal adenocarcinoma (COAD). This study aimed to develop a novel ER-stress-related prognostic risk model for COAD and provide support for COAD cohorts with different risk score responses to immune checkpoint inhibitor therapies. Methods: TCGA-COAD and GSE39582 were included in this prospective study. Univariate and multivariate Cox analyses were performed to identify prognostic ER stress-related genes (ERSGs). Accordingly, the immune infiltration landscape and immunotherapy response in different risk groups were assessed. Finally, the expression of prognostic genes in 10 normal and 10 COAD tissue samples was verified using reverse transcription-quantitative polymerase chain reaction. Results: Eight prognostic genes were selected to establish an ERSG-based signature in the training set of the TCGA-COAD cohort. The accuracy of this was confirmed using a testing set of TCGA-COAD and GSE39582 cohorts. Gene set variation analysis indicated that differential functionality in high-low-risk groups was related to immune-related pathways. Corresponding to this, CD36, TIMP1, and PTGIS were significantly associated with 19 immune cells with distinct proportions between the different risk groups, such as central memory CD4T cells and central memory CD8T cells. Moreover, the risk score was considered effective for predicting the clinical response to immunotherapy, and the immunotherapy response was significantly and negatively correlated with the risk score of individuals with COAD. Furthermore, the immune checkpoint inhibitor treatment was less effective in the high-risk group, where the expression levels of PD-L1 and tumor immune dysfunction and exclusion scores in the high-risk group were significantly increased. Finally, the experimental results demonstrated that the expression trends of prognostic genes in clinical samples were consistent with the results from public databases. Conclusion: Our study established a novel risk signature to predict the COAD prognosis of patients and provide theoretical support for the clinical treatment of COAD.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Humanos , Prognóstico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Prospectivos , Imunoterapia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia
15.
Eur J Pharmacol ; 961: 176137, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37939989

RESUMO

Reverse cholesterol transport (RCT) offers a practical approach to mitigating atherosclerosis. Paeoniflorin, a monoterpenoid glycoside found in plants of the Paeoniaceae family, has shown various effects on cardiovascular and liver diseases. Nevertheless, its impact on atherosclerosis in vivo remains poorly understood. The objective of this study is to examine the effect of paeoniflorin on atherosclerosis using apolipoprotein E-deficient (ApoE-/-) mice and explore the underlying mechanisms, with a specific focus on its modulation of RCT. ApoE-/- mice were continuously administered paeoniflorin by gavage for three months. We assessed lipid parameters in serum and examined pathological changes and gene expressions related to RCT pathways in the aorta, liver, and intestine. In an in vitro study, we utilized RAW264.7 macrophages to investigate the inhibitory effect of paeoniflorin on foam cell formation and its potential to promote RCT. The results revealed that paeoniflorin reduced atherosclerosis, alleviated hyperlipidemia, and mitigated hepatic steatosis. Paeoniflorin may promote RCT by stimulating cholesterol efflux from macrophages via the liver X receptor alpha pathway, enhancing serum high-density lipoprotein cholesterol and apolipoprotein A-I levels, and regulating key genes in hepatic and intestinal RCT. Additionally, treatment ApoE-/- mice with paeoniflorin suppressed the expression of inflammation-related genes, including CD68, tumor necrosis factor alpha, and monocyte chemoattractant protein-1, and mitigated oxidative stress in both the aorta and liver. Our results indicated that paeoniflorin has the potential to be a more effective and safer treatment for atherosclerosis, thanks to its promotion of RCT and its anti-inflammatory and anti-oxidative effects.


Assuntos
Aterosclerose , Colesterol , Animais , Camundongos , Colesterol/metabolismo , Aterosclerose/metabolismo , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Apolipoproteínas E/genética , Camundongos Endogâmicos C57BL
16.
Sci Rep ; 13(1): 18708, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907559

RESUMO

Studies on the association between depression and self-reported endometriosis are limited, and further studies are required to investigate this association. Data were collected from the National Health and Nutrition Examination Survey database (2005-2006). Based on the inclusion and exclusion criteria, 100 participants with self-reported endometriosis and 1295 participants without self-reported endometriosis were included, representing a total population of 64,989,430. Depression severity was assessed using the Patient Health Questionnaire 9 (PHQ9). A survey-weighted logistic regression analysis was performed to explore the association between depression and endometriosis. Subgroup analyses were conducted to explore heterogeneity. The prevalence of endometriosis was 7.17%. A significant positive association was found between the PHQ9 score and endometriosis. After adjusting for all covariates, the PHQ9 score positively correlated with endometriosis. Furthermore, compared with the participants without depression, those with moderate depression were more prone to have endometriosis both in unadjusted and fully adjusted model. However, the relationship between severe depression and endometriosis was not significant in all models (P > 0.05). Our findings highlight the influence of depression on the prevalence of self-reported endometriosis. Further studies are required to elucidate the causal relationship between depression and self-reported endometriosis.


Assuntos
Transtorno Depressivo , Endometriose , Feminino , Humanos , Endometriose/complicações , Endometriose/epidemiologia , Endometriose/diagnóstico , Inquéritos Nutricionais , Depressão/epidemiologia , Depressão/etiologia , Inquéritos e Questionários
17.
Int J Clin Health Psychol ; 23(4): 100389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829189

RESUMO

Background/objective: Patients with major depressive disorder (MDD) have altered learning rates for rewards and losses in non-social learning paradigms. However, it is not well understood whether the ability to learn from social interactions is altered in MDD patients. Using reinforcement learning during the repeated Trust Game (rTG), we investigated how MDD patients learn to trust newly-met partners in MDD patients. Method: Sixty-eight MDD patients and fifty-four controls each played as 'investor' and interacted with ten different partners. We manipulated both the level of trustworthiness by varying the chance of reciprocity (10, 30, 50, 70 and 90%) and reputation disclosure, where partners' reputation was either pre-disclosed or hidden. Results: Our reinforcement learning model revealed that MDD patients had significantly higher learning rates for losses than the controls in both the reputation disclosure and non-disclosure condition. The difference was larger when reputation was not disclosed than disclosed. We observed no difference in learning rates for gains in either condition. Conclusions: Our findings highlight that abnormal learning for losses underlies the social learning process in MDD patients. This abnormality is higher when situational unpredictability is high versus low. Our findings provide novel insights into social rehabilitation of MDD.

18.
Front Public Health ; 11: 1157606, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818303

RESUMO

Aim: This study aims to establish a nomogram model to predict the relevance of SA in Chinese female patients with mood disorder (MD). Method: The study included 396 female participants who were diagnosed with MD Diagnostic Group (F30-F39) according to the 10th Edition of Disease and Related Health Problems (ICD-10). Assessing the differences of demographic information and clinical characteristics between the two groups. LASSO Logistic Regression Analyses was used to identify the risk factors of SA. A nomogram was further used to construct a prediction model. Bootstrap re-sampling was used to internally validate the final model. The Receiver Operating Characteristic (ROC) curve and C-index was also used to evaluate the accuracy of the prediction model. Result: LASSO regression analysis showed that five factors led to the occurrence of suicidality, including BMI (ß = -0.02, SE = 0.02), social dysfunction (ß = 1.72, SE = 0.24), time interval between first onset and first dose (ß = 0.03, SE = 0.01), polarity at onset (ß = -1.13, SE = 0.25), and times of hospitalization (ß = -0.11, SE = 0.06). We assessed the ability of the nomogram model to recognize suicidality, with good results (AUC = 0.76, 95% CI: 0.71-0.80). Indicating that the nomogram had a good consistency (C-index: 0.756, 95% CI: 0.750-0.758). The C-index of bootstrap resampling with 100 replicates for internal validation was 0.740, which further demonstrated the excellent calibration of predicted and observed risks. Conclusion: Five factors, namely BMI, social dysfunction, time interval between first onset and first dose, polarity at onset, and times of hospitalization, were found to be significantly associated with the development of suicidality in patients with MD. By incorporating these factors into a nomogram model, we can accurately predict the risk of suicide in MD patients. It is crucial to closely monitor clinical factors from the beginning and throughout the course of MD in order to prevent suicide attempts.


Assuntos
Nomogramas , Ideação Suicida , Humanos , Feminino , Fatores de Risco , Tentativa de Suicídio , Transtornos do Humor/epidemiologia
19.
Ying Yong Sheng Tai Xue Bao ; 34(9): 2555-2565, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37899123

RESUMO

Taihu Lake has officially implemented the full fishing ban policy since October 1, 2020. We investigated fish community of Taihu Lake in the four seasons of 2020. A total of 42 fish species were collected, belonging to 6 orders, 7 families, and 33 genera. The first five dominant species ranked by the index of relative importance were Coilia nasus, Toxabramis swinhonis, Hypophthalmichthys molitrix, Hypophthalmichthys nobilis, and Salangichthys tangkahkeii. The number of C. nasus accounted for 85.1% of the total number of catches. According to the distributional characteristics of cyanobacterial blooms and aquatic plants, Taihu Lake could be divided into the northern, central, and eastern regions. There was no significant difference in catch per unit effort (CPUE) among different lake regions, but Shannon diversity index and Pielou evenness index in the eastern region was greater than in the other two regions. The CPUE, Shannon diversity index, and Pielou evenness index were significantly different among the four seasons, with the lowest CPUE in autumn and higher diversity in autumn and winter than in spring and summer. Electrical conductivity, water depth, chloride, and transparency were the main environmental factors driving the seasonal variations of fish community in Taihu Lake, while electrical conductivity, dissolved oxygen, total alkalinity, and transparency were key variables driving the spatial patterns. The results could be used as the baseline data for fish community studies in Taihu Lake after the fishing ban.


Assuntos
Cianobactérias , Lagos , Humanos , Animais , Lagos/química , Caça , Água , Estações do Ano , China , Monitoramento Ambiental
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(8): 1203-1209, 2023 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37875360

RESUMO

OBJECTIVES: At present, there are many reports about the treatment of cricopharyngeal achalasia by injecting botulinum toxin type A (BTX-A) into cricopharyngeal muscle guided by ultrasound, electromyography or CT in China, but there is no report about injecting BTX-A into cricopharyngeal muscle guided by endoscope. This study aims to evaluate the efficacy of endoscopic BTX-A injection combined with balloon dilatation in the treatment of cricopharyngeal achalasia after brainstem stroke, and to provide a better method for the treatment of dysphagia after brainstem stroke. METHODS: From June to December 2022, 30 patients with cricopharyngeal achalasia due to brainstem stroke were selected from the Department of Rehabilitation Medicine, the First Hospital of Changsha. They were randomly assigned into a control group and a combined group, 15 patients in each group. Patients in both groups were treated with routine rehabilitation therapy, while patients in the control group were treated with balloon dilatation, and patients in the combined group were treated with balloon dilatation and BTX-A injection. Before treatment and after 2 weeks of treatment, the patients were examined by video fluoroscopic swallowing study, Penetration-aspiration Scale (PAS), Dysphagia Outcome Severity Scale (DOSS), and Functional Oral Intake Scale (FOIS) were used to assess the swallowing function. RESULTS: In the combined group, 1 patient withdrew from the treatment because of personal reasons. Two weeks after treatment, the scores of DOSS, PAS, and FOIS in both groups were better than those before treatment (all P<0.01), and the combined group was better than the control group (all P<0.001). The effective rate was 85.7% in the combined group and 66.7% in the control group, with no significant difference between the 2 groups (P>0.05). CONCLUSIONS: BTX-A injection combined with balloon dilatation is more effective than balloon dilatation alone in improving swallowing function and is worthy of clinical application.


Assuntos
Toxinas Botulínicas Tipo A , Infartos do Tronco Encefálico , Transtornos de Deglutição , Acalasia Esofágica , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Acalasia Esofágica/complicações , Acalasia Esofágica/tratamento farmacológico , Dilatação/efeitos adversos , Toxinas Botulínicas Tipo A/uso terapêutico , Infartos do Tronco Encefálico/complicações , Infartos do Tronco Encefálico/tratamento farmacológico , Resultado do Tratamento
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