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1.
BMC Cancer ; 24(1): 321, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454345

RESUMO

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia de Consolidação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto
2.
Artigo em Inglês | MEDLINE | ID: mdl-38401065

RESUMO

Objective: Trigeminal neuralgia (TN) is very common in the middle-aged and elderly population and seriously affects the normal life of patients. This study aims to analyze the therapeutic effect of percutaneous balloon compression (PBC) on TN and to explore the clinical significance of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), which not only can provide a reference for the clinical treatment of TN in the future, but also can help the clinic to find a reliable indicator for the assessment of TN condition. Methods: The length of stay, total cost of hospitalization, and adverse reactions during treatment were compared between the two groups. Patients were subjected to assessments or investigations of the Barrow Neurological Institute (BNI) scale, Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) before and after treatment. In addition, NLRP3 in the peripheral blood of patients in the research group was measured, and the correlation of NLRP3 with BNI score and prognosis for recurrence was analyzed. Results: The length of stay and the total cost of hospitalization were respectively (12.10±2.20) d and (26445.96±5553.78) yuan in the research group, significantly reduced than those in the control group (P < .05). And the BNI score, PSQI and SAS/SDS were lower in the research group after treatment (P < .05), but the incidence of facial numbness, herpes orofacialis and masticatory muscle weakness were higher in the research group than in the control group (P < .05). After treatment, NLRP3 decreased in the research group, which was positively correlated with BNI score (P < .05). In addition, NLRP3 showed an excellent effect in predicting recurrence. Conclusion: PBC effectively improved the pain and negative psychological status of patients with TN, and NLRP3 was closely related to the pain of patients with TN. In the future, PBC is used in the clinic to treat TN and improve the prognosis of patients.

3.
J Gastroenterol Hepatol ; 38(9): 1520-1529, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37202867

RESUMO

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.


Assuntos
Neoplasias do Colo , Humanos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/cirurgia , Composição Corporal , Inflamação/diagnóstico por imagem , Inflamação/etiologia , Nomogramas , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Tomografia
4.
Stress ; 25(1): 166-178, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35435121

RESUMO

Patients with post-traumatic stress disorder (PTSD) are usually at an increased risk for chronic disorders, such as irritable bowel syndrome (IBS), characterized by hyperalgesia and allodynia, but its subsequent effect on visceral hyperalgesia and the mechanism remain unclear. The present study employed single prolonged stress (SPS), a model of PTSD-pain comorbidity, behavioral evaluation, intrathecal drug delivery, immunohistochemistry, Western blotting, and RT-PCR techniques. When detecting visceral sensitivity, the score of the abdominal withdrawal reflex (AWR) induced by graded colorectal distention (CRD) was used. The AWR score was reduced in the SPS day 1 group but increased in the SPS day 7 and SPS day 14 groups at 40 mmHg and 60 mmHg, and the score was increased significantly with EphrinB1-Fc administration. The EphB2+ cell density and EphB2 protein and mRNA levels were downregulated in the SPS day 1 group and then upregulated significantly in the SPS day 7 group; these changes were more noticeable with EphrinB1-Fc administration compared with the SPS-only group. The C-Fos-positive reaction induced by SPS was mainly localized in neurons of the spinal dorsal horn, in which the C-Fos-positive cell density and its protein and mRNA levels were upregulated on SPS days 7 and 14; these changes were statistically significant in the SPS + EphrinB1-Fc group compared with the SPS alone group. The present study confirmed the time window for the AWR value, EphB2 and C-Fos changes, and the effect of EphrinB1-Fc on these changes, which suggests that spinal cord EphB2 activation exacerbates visceral pain after SPS.


Assuntos
Hiperalgesia , Dor Visceral , Animais , Hiperalgesia/genética , Hiperalgesia/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor EphB2/genética , Receptor EphB2/metabolismo , Medula Espinal/metabolismo , Estresse Psicológico , Dor Visceral/genética , Dor Visceral/metabolismo
5.
J Transl Med ; 19(1): 216, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016142

RESUMO

BACKGROUND: Eukaryotic translation initiation factor 6 (eIF6) has a crucial function in the maturation of 60S ribosomal subunits, and it controls the initiation of protein translation. Although emerging studies indicate that eIF6 is aberrantly expressed in various types of cancers, the functions and underlying molecular mechanisms of eIF6 in the pathological progression of hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the potential diagnostic and prognostic value of eIF6 in patients with HCC. METHODS: HCC samples enrolled from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and our cohort were used to explore the role and mechanism of eIF6 in HCC. The diagnostic power of eIF6 was verified by receiver operating characteristic curve (ROC) analysis and its prognostic value was assessed by Kaplan-Meier analysis, and then related biological functions of eIF6 were determined in vitro and in vivo cancer models. In addition, potential molecular mechanism of eIF6 in HCC was unveiled by the gene set enrichment analysis and western blot assay. RESULTS: We demonstrated that eIF6 expression was markedly increased in HCC, and elevated eIF6 expression correlated with pathological progression of HCC. Besides, eIF6 served as not only a new diagnostic biomarker but also an independent risk factor for OS in HCC patients. Functional studies indicated that the deletion of eIF6 displayed tumor-suppressor activity in HCC cells. Furthermore, we found that eIF6 could activate the mTOR-related signaling pathway and regulate the expression level of its target genes, such as CCND1, CDK4, CDK6, MYC, CASP3 and CTNNBL1, and these activities promoted proliferation and invasion of HCC cells. CONCLUSIONS: The findings of this study provided a novel basis for understanding the potential role of eIF6 in promoting tumor growth and invasion, and exploited a promising strategy for improving diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Fatores de Iniciação em Eucariotos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
6.
Neurochem Res ; 46(7): 1659-1673, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33770320

RESUMO

Parvalbumin-immunoreactive (Parv+) interneurons is an important component of striatal GABAergic microcircuits, which receive excitatory inputs from the cortex and thalamus, and then target striatal projection neurons. The present study aimed to examine ultrastructural synaptic connection features of Parv+ neruons with cortical and thalamic input, and striatal projection neurons by using immuno-electron microscopy (immuno-EM) and immunofluorescence techniques. Our results showed that both Parv+ somas and dendrites received numerous asymmetric synaptic inputs, and Parv+ terminals formed symmetric synapses with Parv- somas, dendrites and spine bases. Most interestingly, spine bases targeted by Parv+ terminals simultaneously received excitatory inputs at their heads. Electrical stimulation of the motor cortex (M1) induced higher proportion of striatal Parv+ neurons express c-Jun than stimulation of the parafascicular nucleus (PFN), and indicated that cortical- and thalamic-inputs differentially modulate Parv+ neurons. Consistent with that, both Parv + soma and dendrites received more VGlut1+ than VGlut2+ terminals. However, the proportion of VGlut1+ terminal targeting onto Parv+ proximal and distal dendrites was not different, but VGlut2+ terminals tended to target Parv+ somas and proximal dendrites than distal dendrites. These functional and morphological results suggested excitatory cortical and thalamic glutamatergic inputs differently modulate Parv+ interneurons, which provided inhibition inputs onto striatal projection neurons. To maintain the balance between the cortex and thalamus onto Parv+ interneurons may be an important therapeutic target for neurological disorders.


Assuntos
Córtex Cerebral/ultraestrutura , Dendritos/ultraestrutura , Interneurônios/ultraestrutura , Núcleos Intralaminares do Tálamo/ultraestrutura , Parvalbuminas/metabolismo , Sinapses/ultraestrutura , Animais , Córtex Cerebral/metabolismo , Dendritos/metabolismo , Interneurônios/metabolismo , Núcleos Intralaminares do Tálamo/metabolismo , Masculino , Ratos Sprague-Dawley , Sinapses/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
7.
Minim Invasive Ther Allied Technol ; 29(2): 90-97, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30849259

RESUMO

Introduction: This study evaluated the accuracy of endoscopic ultrasound (EUS) for preoperative staging of rectal cancer and guiding the treatment of transanal endoscopic microsurgery (TEM) in early rectal cancer.Material and methods: One-hundred-twenty-six patients with rectal cancer were staged preoperatively using EUS and the results were compared with postoperative histopathology results. Radical surgeries, including low anterior resection (LAR), abdominal-perineal resection (APR) and Hartmann surgeries, were performed on patients with advanced rectal cancers, and TEM was performed on patients with stage T1. The Kappa statistic was used to determine agreement between EUS-based staging and pathology staging.Results: The overall accuracies of EUS for T and N stage were 90.8% (Kappa = 0.709) and 76.7% (Kappa = 0.419), respectively. The accuracies of EUS for uT1, uT2, uT3, and uT4 stages were 96.8%, 92.1%, 84.1%, and 88.9%, respectively, and for uN0, uN1, and uN2 stages, they were 71.9%, 64.9%, and 93.0%, respectively. Twelve patients underwent TEM and received confirmed pathology results of early rectal cancer. After postoperative follow-up, there were no local recurrences or distant metastases.Conclusion: EUS is a good and comparable technique for postoperative staging of rectal cancer. Moreover, EUS is used as indicator for preoperative staging and tumor assessment strategy when considering TEM.


Assuntos
Endossonografia/métodos , Neoplasias Retais/cirurgia , Microcirurgia Endoscópica Transanal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reto/cirurgia
8.
Neurochem Res ; 44(5): 1079-1089, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30715657

RESUMO

Dopaminergic neuron degeneration is known to give rise to dendrite injury and spine loss of striatal neurons, however, changes of intrastriatal glutamatergic terminals and their synapses after 6-hydroxydopamine (6OHDA)-induced dopamine (DA)-depletion remains controversial. To confirm the effect of striatal DA-depletion on the morphology and protein levels of corticostriatal and thalamostriatal glutamatergic terminals and synapses, immunohistochemistry, immuno-electron microscope (EM), western blotting techniques were performed on Parkinson's disease rat models in this study. The experimental results of this study showed that: (1) 6OHDA-induced DA-depletion resulted in a remarkable increase of Vesicular glutamate transporter 1 (VGlut1) + and Vesicular glutamate transporter 2 (VGlut2)+ terminal densities at both the light microscope (LM) and EM levels, and VGlut1+ and VGlut2+ terminal sizes were shown to be enlarged by immuno-EM; (2) Striatal DA-depletion resulted in a decrease in both the total and axospinous terminal fractions of VGlut1+ terminals, but the axodendritic terminal fraction was not significantly different from the control group. However, total, axospinous and axodendritic terminal fractions for VGlut2+ terminals declined significantly after striatal DA-depletion. (3) Western blotting data showed that striatal DA-depletion up-regulated the expression levels of the VGlut1 and VGlut2 proteins. These results suggest that 6OHDA-induced DA-depletion affects corticostriatal and thalamostriatal glutamatergic synaptic inputs, which are involved in the pathological process of striatal neuron injury induced by DA-depletion.


Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Doença de Parkinson/metabolismo , Sinapses/metabolismo , Animais , Córtex Cerebral/metabolismo , Espinhas Dendríticas/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neostriado/metabolismo , Terminações Pré-Sinápticas/metabolismo , Ratos , Tálamo/metabolismo
9.
J Surg Res ; 242: 31-39, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31059947

RESUMO

BACKGROUND: This study aimed to establish a three-dimensional model of infrapyloric vessels using the Hisense computer-assisted surgery (CAS) system before the operation to understand blood vessel variation types and determine the group 6 lymph node (LN) metastasis status. METHODS: One hundred and four gastric cancer patients were randomly assigned to a CAS group and a computed tomography (CT) group. Intraoperative and postoperative complications in the two groups were recorded. The number of group 6 LNs dissected and the metastasis status were compared between the groups. The independent risk factors influencing group 6 LN metastasis were determined by multiple logistic regression analysis. RESULTS: In the 50 CAS group patients, the gastrocolic trunk of Henle was divided into a gastrocolic type (34.0%) and a gastropancreatic colonic type (66.0%); the right gastroepiploic artery was divided into a coarse blood supply type (24.0%) and a fine blood supply type (76.0%); and the relationship between the right gastroepiploic artery and right gastroepiploic vein was divided into an adjacent type (58.0%) and a separated type (42.0%). Although the difference was not significant, the CAS group had fewer cases of intraoperative gastrocolic trunk injury and postoperative pancreatic leakage in trend than the CT group. The CAS group had more dissected LNs (P < 0.001) and metastatic LNs (P = 0.011) than the CT group; meanwhile, it had higher LN metastasis rate and LN metastasis degree in trend than the CT group. According to the multiple logistic regression model, tumor location and TNM stage were significantly correlated with group 6 LN metastases. CONCLUSIONS: By establishing a three-dimensional model of the infrapyloric vessels using the Hisense CAS system, we comprehensively determined the anatomic variations in each collateral vessel. The application of the Hisense CAS system significantly improved the number of LNs dissected and the discovery rate of LN metastases without increasing the incidence of complications.


Assuntos
Carcinoma/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Feminino , Humanos , Imageamento Tridimensional , Modelos Logísticos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Estadiamento de Neoplasias , Estudos Prospectivos , Antro Pilórico , Método Simples-Cego , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X
10.
Hepatogastroenterology ; 61(131): 880-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26176090

RESUMO

BACKGROUND/AIMS: To observe the effects of DcR3 gene on the occurrence and progression of gastric cancer and explore its mechanism. METHODOLOGY: DcR3 mRNA expressions in both gastric normal tissue and gastric cancer tissue were detected with RT-PCR. Apoptosis index (AI) was determined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: Positive rate of DcR3 mRNA expression was significantly higher in gastric cancer tissue than in gastric normal tissue (P < 0.01). The level of DcR3 mRNA expression was related to differentiation, lymphatic metastasis and TNM staging (P < 0.05). The level of DcR3 mRNA expression was inversely correlated with AI (P < 0.01). CONCLUSION: DcR3 plays an important role in the occurrence and progression of gastric cancer possibly through inhibiting gastric cancer cell apoptosis.


Assuntos
Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Apoptose , Estudos de Casos e Controles , Diferenciação Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/análise , Neoplasias Gástricas/patologia
11.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 166994, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38141838

RESUMO

Radiation injury of blood vessels (RIBV) is a serious long-term complication of radiotherapy, characterized by the development of atherosclerosis. The involvement of vascular smooth muscle cells (VSMCs) senescence in the pathogenesis of radiation-induced atherosclerosis has been implicated, yet the precise mechanisms governing VSMCs senescence remain inadequately comprehended. In this study, the senescence of VSMCs was examined by employing SA-ß-gal staining and assessing the expression of p16 and p21, both in vivo and in vitro. Our findings revealed that ionizing radiation (IR) has the potential to augment cellular senescence. In addition, IR significantly activated the NF-κB pathway, as evidenced by increased p65 nuclear translocation, phospho-p65 expression, and enhanced binding ability of p65 (EMSA). Furthermore, a decrease in HMGB2 expression following exposure to IR was observed via Western blot analysis, while CTCF expression remained unchanged. Interestingly, the formation of CTCF spatial clustering was detected under super-resolution fluorescence microscopy. Concurrently, the ChIP technique identified the facilitation of the interaction between CTCF and p16 gene through IR. The inhibition of CTCF or the overexpression of HMGB2 through lentiviruses effectively eliminates the formation of CTCF clusters and the upregulation of p16 and p21 after IR. Inhibition of NF-κB activation induced by IR by PDTC (100 µM) led to a decrease in the staining of SA-ß-gal, a reduction in p16 expression, an increase in HMGB2 protein expression and a decrease in CTCF clusters formation. This study provided significant insights into the role and mechanism of IR in VSMCs senescence by regulating NF-κB/CTCF/p16 pathway.


Assuntos
Aterosclerose , NF-kappa B , Humanos , NF-kappa B/metabolismo , Músculo Liso Vascular/metabolismo , Proteína HMGB2/metabolismo , Proteína HMGB2/farmacologia , Senescência Celular , Radiação Ionizante , Aterosclerose/metabolismo
12.
Neuropsychopharmacology ; 49(8): 1318-1329, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38438592

RESUMO

Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.


Assuntos
Depressão , Camundongos Endogâmicos C57BL , Vias Neurais , Optogenética , Córtex Pré-Frontal , Derrota Social , Estresse Psicológico , Animais , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/fisiopatologia , Masculino , Depressão/fisiopatologia , Vias Neurais/fisiopatologia , Camundongos , Núcleo Mediodorsal do Tálamo , Neurônios/fisiologia , Neurônios/metabolismo , Células Piramidais/fisiologia
13.
Neurobiol Stress ; 31: 100654, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38948390

RESUMO

Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.

14.
Transl Psychiatry ; 14(1): 149, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493173

RESUMO

Chronic stress-induced anxiodepression is a common health problem, however its potential neurocircuitry mechanism remains unclear. We used behavioral, patch-clamp electrophysiology, chemogenetic, and optogenetic approaches to clarify the response of the lateral hypothalamus (LH) and the medial prefrontal cortex (mPFC) to stress, confirmed the structural connections between the LH and mPFC, and investigated the role of the LH-mPFC pathway in chronic stress-induced anxiodepression symptoms. Unpredictable chronic mild stress (UCMS) caused anxiodepression-like behaviors, including anxiety, anhedonia, and despair behaviors. We discovered that the activity of the LH and mPFC was both increased after restraint stress (RS), a stressor of UCMS. Then we found that the orexinergic neurons in the LH predominantly project to the glutamatergic neurons in the mPFC, and the excitability of these neurons were increased after UCMS. In addition, overactivated LH orexinergic terminals in the mPFC induced anhedonia but not anxiety and despair behaviors in naive mice. Moreover, chemogenetically inhibited LH-mPFC orexinergic projection neurons and blocked the orexin receptors in the mPFC alleviated anhedonia but not anxiety and despair behaviors in UCMS-treated mice. Our study identified a new neurocircuit from LH orexinergic neurons to mPFC and revealed its role in regulating anhedonia in response to stress. Overactivation of LHOrx-mPFC pathway selectively mediated chronic stress-induced anhedonia. In normal mice, the LHOrx-mPFC pathway exhibits relatively low activity. However, after chronic stress, the activity of orexinergic neuron in LH is overactivated, leading to an increased release of orexin into the mPFC. This heightened orexin concentration results in increased excitability of the mPFC through OX1R and OX2R, consequently triggering anhedonia.


Assuntos
Anedonia , Região Hipotalâmica Lateral , Camundongos , Animais , Região Hipotalâmica Lateral/metabolismo , Orexinas/metabolismo , Ansiedade , Córtex Pré-Frontal/metabolismo
15.
Heliyon ; 10(6): e27637, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38510046

RESUMO

Introduction: The typical functionality of astrocytes was previously shown to be disrupted by Parkinson's disease (PD), which actively regulates synaptic neurotransmission. However, the morphological changes in astrocytes wrapping glutamatergic synapses in the striatum after dopamine (DA) neuronal degeneration is unclear. Methods: We utilized a range of methodologies, encompassing the 6-hydroxydopamine (6OHDA)-induced PD model, as well as techniques such as immunohistochemistry, Western blotting, immunofluorescence and immunoelectron microscopy (IEM) to delve into the consequences of DA neuronal degeneration on the morphological attributes of perisynaptic astrocytes. Results: Our findings demonstrated a notable rise in glial fibrillary acidic protein (GFAP) + astrocyte density and an upregulation in GFAP protein expression within the striatum due to DA neuronal degeneration, coincided with the enlargement, elongation, and thickening of astrocyte protuberances. However, the expression levels of glutamate transporter 1 (GLT1) and glutamine synthetase (GS), which are related to glutamate-glutamine cycle, were significantly reduced. Double immunofluorescence and IEM results indicated that different proportions of vesicular glutamate transporter 1 (VGlut1)+ and vesicular glutamate transporter 2 (VGlut2) + terminals were wrapped by astrocytes. Additionally, DA neuronal degeneration increased the percentage and area of VGlut1+ and VGlut2+ terminals wrapped by GFAP + astrocytes in the striatum. Furthermore, we noted that DA neuronal degeneration increased the percentage of VGlut1+ and VGlut2+ axo-spinous synapses wrapped by astrocytes but had no effect on axo-dendritic synapses. Conclusion: Hence, perisynaptic astrocytes wrapping striatal glutamatergic synapses exhibit substantial morphological and functional alterations following DA neuronal degeneration making them a potential target for therapeutic interventions in PD.

16.
J Hand Surg Am ; 38(4): 672-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23474158

RESUMO

PURPOSE: Both passive flexion-active extension and active rehabilitation have shown advantages and disadvantages in tendon healing. The purpose of this study was to measure the effect of a combination of these 2 rehabilitation protocols. METHODS: A tendon injury model was used in white Leghorn chickens. Thirty-two animals were randomly assigned into 4 groups. We compared an unrestricted active flexion rehabilitation (UA) group with 3 groups starting passive flexion, active extension, and active flexion (PAA) at 5, 9.5 and 14 days after repair. The tensile properties and range of motion of the 3 interphalangeal joints were evaluated for 3 postoperative weeks. RESULTS: In terms of tensile properties of the operated foot, PAA-14 was higher than any other group, and PAA-5 was the lowest. There was no significant difference between the PAA-9.5 and UA. For the range of motion, there were significant differences between all 4 groups: UA increased the most, PAA-14 increased the least, and PAA-5 increased more than PAA-9.5. For the rupture rate, UA and PAA-5 were higher than were PAA-9.5 and PAA-14. CONCLUSIONS: The results indicate that the PAA-9.5 and UA may give the best balance (tensile properties, range of motion, rupture rates) of these rehabilitation protocols. PPA-9.5 and UA had similar moderate tensile properties. When considering an increased range of motion, the UA method may be the most appropriate despite its higher rupture rate. When considering a lower rupture rate, PAA-9.5 may be the most suitable. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.


Assuntos
Terapia por Exercício/métodos , Procedimentos Ortopédicos/métodos , Amplitude de Movimento Articular/fisiologia , Traumatismos dos Tendões/reabilitação , Traumatismos dos Tendões/cirurgia , Análise de Variância , Animais , Fenômenos Biomecânicos , Galinhas , Terapia Combinada , Modelos Animais de Doenças , Traumatismos dos Dedos/reabilitação , Traumatismos dos Dedos/cirurgia , Cuidados Pós-Operatórios/métodos , Distribuição Aleatória , Resistência à Tração
17.
PLoS One ; 18(5): e0284803, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37196019

RESUMO

China is in a critical stage of economic growth mode transformation. The digital transformation of the manufacturing industry may create new impetus and new models for economic growth. Taking the manufacturing industry of 25 prefecture-level cities in the Yangtze River Delta region as the research object, we explore the digital transformation process of the manufacturing industry and verifies its theoretical mechanism of promoting economic growth through the industrial structure. A panel model based on the improved Feder two-sector model and a multiple mediating effect model are established to explore the dynamic mechanism of manufacturing digital transformation to promote economic growth through industrial restructuring. The results show that the digital transformation of the manufacturing industry in the Yangtze River Delta region of China is relatively high, and the speed of digital transformation has been accelerating in recent years. The digital transformation of the manufacturing industry can promote the change in industrial structure and form a new driving force for economic growth. The key is to improve the level of industrial structure and extend the length of the industrial chain. Based on these, we propose measures to promote the transformation and upgrading of industrial structure for the sustainable development of China's economy.


Assuntos
Desenvolvimento Econômico , Indústrias , Indústria Manufatureira , Cidades , Comércio , China
18.
Micromachines (Basel) ; 14(7)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37512768

RESUMO

In this paper, a P-type GaN buried layer is introduced into the buffer layer of AlGaN/GaN HEMTs, and the effect of the P-type GaN buried layer on the device's temperature characteristics is studied using Silvaco TCAD software. The results show that, compared to the conventional device structure, the introduction of a P-type GaN buried layer greatly weakens the peak of the channel electric field between the gate and drain of the device. This leads to a more uniform electric field distribution, a substantial reduction in the lattice temperature of the device, and a more uniform temperature distribution. Therefore, the phenomenon of negative resistance caused by self-heating effect is significantly mitigated, while the breakdown performance of the device is also notably enhanced.

19.
Front Neural Circuits ; 17: 1086873, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37187913

RESUMO

The cerebral cortex innervates motor neurons in the anterior horn of the spinal cord by regulating of interneurons. At present, nerve tracing, immunohistochemistry, and immunoelectron microscopy are used to explore and confirm the characteristics of synaptic connections between the corticospinal tract (CST) and cervical spinal calretinin (Cr) interneurons. Our morphological results revealed that (1) biotinylated dextran amine labeled (BDA+) fibers from the cerebral cortex primarily presented a contralateral spinal distribution, with a denser distribution in the ventral horn (VH) than in the dorsal horn (DH). An electron microscope (EM) showed that BDA+ terminals formed asymmetric synapses with spinal neurons, and their mean labeling rate was not different between the DH and VH. (2) Cr-immunoreactive (Cr+) neurons were unevenly distributed throughout the spinal gray matter, and were denser and larger in the VH than in the DH. At the single labeling electron microscope (EM) level, the labeling rate of Cr+ dendrites was higher in the VH than in the DH, in which Cr+ dendrites mainly received asymmetric synaptic inputs, and between the VH and DH. (3) Immunofluorescence triple labeling showed obvious apposition points among BDA+ terminals, synaptophysin and Cr+ dendrites, with a higher density in the VH than in the DH. (4) Double labeling in EM, BDA+ terminals and Cr+ dendrites presented the same pattern, BDA+ terminals formed asymmetric synapses either with Cr+ dendrites or Cr negative (Cr-) dendrites, and Cr+ dendrites received either BDA+ terminals or BDA- synaptic inputs. The average percentage of BDA+ terminals targeting Cr+ dendrites was higher in the VH than in the DH, but the percentage of BDA+ terminals targeting Cr- dendrites was prominently higher than that targeting Cr+ dendrites. There was no difference in BDA+ terminal size. The percentage rate for Cr+ dendrites receiving BDA+ terminal inputs was lower than that receiving BDA- terminal inputs, and the BDA+ terminal size was larger than the BDA- terminal size received by Cr+ dendrites. The present morphological results suggested that spinal Cr+ interneurons are involved in the regulatory process of the cortico-spinal pathway.


Assuntos
Neurônios Motores , Sinapses , Ratos , Animais , Calbindina 2/metabolismo , Sinapses/fisiologia , Tratos Piramidais , Córtex Cerebral/metabolismo , Terminações Pré-Sinápticas/metabolismo
20.
Micromachines (Basel) ; 14(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37893385

RESUMO

A GaN high-electron-mobility transistor (HEMT) was simulated using the semiconductor simulation software Silvaco TCAD in this paper. By constructing a two-dimensional structure of GaN HEMT, combined with key models such as carrier mobility, the effects of a different state, different incidence position, different drain voltage, different LET values, and a different incidence angle on the single-event transient effect of GaN HEMT are simulated. LET stands for the linear energy transfer capacity of a particle, which refers to the amount of energy transferred by the particle to the irradiated substance on the unit path. The simulation results show that for GaN HEMTs, the single-event transient effect is more obvious when the device is in off-state than in on-state. The most sensitive location of GaN HEMTs to the single-event effect is in the region near the drain. The peak transient current increases with the increase in the drain bias and incident ion LET values. The drain charge collection time increases with the angle of incidence of heavy ion.

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