Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.416
Filtrar
1.
Artigo em Chinês | MEDLINE | ID: mdl-38563175

RESUMO

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand(group A) and 50 cases underwent routine microscopic tympanoplasty(group B). The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was(65.78±18.21) min, the mean intraoperative blood loss was(12.94±4.46) mL, the postoperative pain score was(1.82±0.60) points, and the mean postoperative hospital stay was(2.76±0.72) d. The mean operation time of group B was(89.45±20.38) min, the mean intraoperative blood loss was(22.78±5.74) mL, the postoperative pain score was(2.98±0.85) points, and the mean postoperative hospital stay was(3.82±0.75) d, which with statistical significance between the two groups(P<0.05). Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery(P<0.05), but there was no significant difference between the two groups before surgery and 6 months after surgery(P>0.05). There were 2 cases in group A(4%) and 1 case in group B(2%) complicated with tympanic cord injury during operation, and the difference was not statistically significant(P>0.05). There were 47 cases of A group(94%) of one-time healing of tympanic membrane after operation, 48 cases(96%) of group B, and the difference was not statistically significant(P>0.05). Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.


Assuntos
Otite Média , Timpanoplastia , Humanos , Timpanoplastia/métodos , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Estudos de Viabilidade , Otite Média/cirurgia , Resultado do Tratamento , Doença Crônica , Endoscopia/métodos , Dor Pós-Operatória
3.
Artigo em Inglês | MEDLINE | ID: mdl-38561861

RESUMO

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

4.
Br J Cancer ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575732

RESUMO

BACKGROUND: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood. METHODS: Mass spectrometry analyses were performed to identify the crotonylation sites of DNA-PKcs in response to γ-ray irradiation. Co-immunoprecipitation (Co-IP), western blotting, in vitro crotonylation assays, laser microirradiation assays, in vitro DNA binding assays, in vitro DNA-PK assembly assays and IF assays were employed to confirm the crotonylation, identify the crotonylase and decrotonylase, and elucidate how crotonylation regulates the activity and function of DNA-PKcs. Subcutaneous xenografts of human HeLa GCN5 WT or HeLa GCN5 siRNA cells in BALB/c nude mice were generated and utilized to assess tumor proliferation in vivo after radiotherapy. RESULTS: Here, we reveal that K525 is an important site of DNA-PKcs for crotonylation, and whose level is sharply increased by irradiation. The histone acetyltransferase GCN5 functions as the crotonylase for K525-Kcr, while HDAC3 serves as its dedicated decrotonylase. K525 crotonylation enhances DNA binding activity of DNA-PKcs, and facilitates assembly of the DNA-PK complex. Furthermore, GCN5-mediated K525 crotonylation is indispensable for DNA-PKcs autophosphorylation and the repair of double-strand breaks in the NHEJ pathway. GCN5 suppression significantly sensitizes xenograft tumors of mice to radiotherapy. CONCLUSIONS: Our study defines K525 crotonylation of DNA-PKcs is important for the DNA-PK complex assembly and DSBs repair activity via NHEJ pathway. Targeting GCN5-mediated K525 Kcr of DNA-PKcs may be a promising therapeutic strategy for improving the outcome of cancer radiotherapy.

5.
PLoS One ; 19(4): e0299119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38598486

RESUMO

The Yangtze River Delta (YRD) bears the vital task of driving the growth of China's equipment manufacturing industry (EMI) intelligence as an advanced region. Fostering the transformation and upgrading of the EMI in the YRD and constructing a modern production mode is vital to developing and reforming China's manufacturing industry. This paper uses industrial robot data to assess the level of intelligence (LoI) in the EMI from 2016 to 2019. The OLS (ordinary least squares) model is used for the measurements, and the MQ (the modified contribution index) is used to estimate the degree of contribution from a host of variables. It is identified that the LoI is on the rise. However, excluding railways, aerospace, shipbuilding, and other transportation equipment manufacturing, the LoI is significantly higher than in other subsectors. It is also identified that technological innovation ability, human capital density, and enterprise cost pressure govern the industry's LoI. Moreover, while there is a difference in the main influencing factors in LoI within different industries, R&D investment, technological innovation ability, and enterprise cost pressure have the most significant impact across most equipment manufacturing sub-industries.


Assuntos
Indústria Manufatureira , Rios , Humanos , Indústrias , Invenções , Comércio , Desenvolvimento Econômico , China
7.
Front Endocrinol (Lausanne) ; 15: 1369968, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567310

RESUMO

Objective: This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result. Results: A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings. Conclusions: LDH can serve as a valuable biomarker for screening DKD in patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Fatores de Risco , Inquéritos Nutricionais , L-Lactato Desidrogenase
8.
Cancer Med ; 13(7): e7158, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572933

RESUMO

BACKGROUND: Thoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood. METHODS: Patients were identified from a Chinese cancer center (FUSCC) (2005-2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed. RESULTS: Totally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy. CONCLUSIONS: LACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Humanos , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/terapia , Carcinoma Adenoide Cístico/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Prognóstico , Nomogramas , Pulmão/patologia
9.
J Neuroeng Rehabil ; 21(1): 47, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575926

RESUMO

Decoding movement intentions from motor unit (MU) activities to represent neural drive information plays a central role in establishing neural interfaces, but there remains a great challenge for obtaining precise MU activities during sustained muscle contractions. In this paper, we presented an online muscle force prediction method driven by individual MU activities that were decomposed from prolonged surface electromyogram (SEMG) signals in real time. In the training stage of the proposed method, a set of separation vectors was initialized for decomposing MU activities. After transferring each decomposed MU activity into a twitch force train according to its action potential waveform, a neural network was designed and trained for predicting muscle force. In the subsequent online stage, a practical double-thread-parallel algorithm was developed. One frontend thread predicted the muscle force in real time utilizing the trained network and the other backend thread simultaneously updated the separation vectors. To assess the performance of the proposed method, SEMG signals were recorded from the abductor pollicis brevis muscles of eight subjects and the contraction force was simultaneously collected. With the update procedure in the backend thread, the force prediction performance of the proposed method was significantly improved in terms of lower root mean square deviation (RMSD) of around 10% and higher fitness (R2) of around 0.90, outperforming two conventional methods. This study provides a promising technique for real-time myoelectric applications in movement control and health.


Assuntos
Contração Muscular , Músculo Esquelético , Humanos , Eletromiografia/métodos , Músculo Esquelético/fisiologia , Contração Muscular/fisiologia , Potenciais de Ação , Redes Neurais de Computação
10.
Sci Total Environ ; 927: 172171, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575035

RESUMO

Rocky desertification is one of the most ecological problems in the karst context. Although extensive research has been conducted to explore how to restore and protect, the responses of soil fungi and archaea to rocky desertification succession remain limited. Here, four grades of rocky desertification in a karst ecosystem were selected, amplicon sequencing analysis was conducted to investigate fungal and archaeal community adaptation in response to rocky desertification succession. Our findings revealed that the diversity and community structure of fungi and archaea in soils declined with the aggravation of rocky desertification. As the rocky desertification succession intensified, microbial interactions shifted from cooperation to competition. Microbial survival strategies were K-strategist and r-strategist dominated in the early and late stages of succession, respectively. Additionally, the driving factors affecting microorganisms have shifted from vegetation diversity to soil properties as the intensification of rocky desertification. Collectively, our study highlighted that plant diversity and soil properties play important roles on soil microbiomes in fragile karst ecosystems and that environmental factors induced by human activities might still be the dominant factor exacerbating rocky desertification, which could significantly enrich our understanding of microbial ecology within karst ecosystems.


Assuntos
Fungos , Microbiota , Microbiologia do Solo , Solo , Solo/química , Archaea/genética , Archaea/fisiologia , Ecossistema , Conservação dos Recursos Naturais
11.
bioRxiv ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38659780

RESUMO

Background and Aims: Since the role of hepatic progenitor cells (HPCs) constituting ductular reactions in pathogenesis remains ambiguous, we aimed to establish the in vivo cause-and-effect relationship between HPCs and angiogenesis, a process associated with chronic liver disease progression. We previously demonstrated that peritumoral ductules are associated with angiogenesis in liver tumors and forkhead box L1 (Foxl1)- expressing murine HPCs secrete angiogenic factors in vitro. Therefore, we hypothesized that HPCs are capable of remodeling the vascular microenvironment and this function of HPCs is dependent on recombination signal binding protein for immunoglobulin kappa J region (RBPJ), a key effector of the Notch signaling pathway. Approach and Results: We generated HPC-specific Rbpj conditional knockout mice using Foxl1-Cre and treated them with the 3,5-diethoxycarbonyl-1,4-dihydrocollidine-supplemented diet to induce cholestatic liver disease. Knockout mice displayed significant reduction of HPC proliferation and ductular reactions as well as attenuated vascular and fibrotic areas compared to control mice. Assessment of vascular endothelial growth factor A-positive areas in vivo and the effects of Rbpj shRNAs in vitro indicated that Rbpj knockout in HPCs reduces the total number of angiogenic factor-expressing cells rather than affecting angiogenic factor expression within HPCs. Single-nucleus RNA sequencing analysis indicated that conditional Rbpj knockout in HPCs induces transcriptional changes in endothelial cells and alters expression of genes involved in various functions of the endothelium. Conclusion: Our findings indicate that HPCs regulate endothelial responses to cholestatic liver disease and Rbpj deletion in HPCs attenuates these responses, identifying novel targets for modulating angiogenesis during disease progression.

12.
MedComm (2020) ; 5(5): e542, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38660685

RESUMO

Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor-promoting effect of senescence is mainly elicited by a senescence-associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A "one-two-punch" therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38625835

RESUMO

Hypertrophic cardiomyopathy is an important cause of heart failure and arrhythmias, including sudden death, with a major impact on the healthcare system. Genetic causes and different phenotypes are now increasingly being identified for this condition. In addition, specific medications, such as myosin inhibitors, have been recently shown as potentially able to modify its symptoms, hemodynamic abnormalities and clinical course. Our article aims to provide a comprehensive outline of the epidemiology, diagnosis and treatment of hypertrophic cardiomyopathy in the current era.

14.
Chin Med ; 19(1): 63, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654354

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus, contributing to end-stage renal disease with limited treatment options. The development of DKD is attributed to podocyte injury resulting from abnormal podocyte autophagy. Consequently, the restoration of podocyte autophagy is deemed a practicable approach in the treatment of DKD. METHODS: Diabetic mice were induced by streptozotocin and high-fat diet feeding. Following 8 weeks of "QN" agarwood treatment, metrics such as albuminuria, serum creatinine (Scr), and blood urea nitrogen (BUN) were evaluated. Renal histological lesions were evaluated by H&E, PAS, Masson, and Sirius red staining. Evaluation of the effects of "QN" agarwood on renal inflammation and fibrosis in DKD mice through WB, q-PCR, and IHC staining analysis. Cytoscape 3.7.1 was used to construct a PPI network. With the DAVID server, the gene ontology (GO) functional annotation and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the target enrichment were performed. Molecular docking and binding affinity calculations were conducted using AutoDock, while PyMOL software was employed for visualizing the docking results of active compounds and protein targets. RESULTS: The results of this study show that "QN" agarwood reduced albuminuria, Scr, and BUN in DKD mice, and improved the renal pathological process. Additionally, "QN" agarwood was observed to downregulate the mRNA and protein expression levels of pro-inflammatory and pro-fibrotic factors in the kidneys of DKD mice. Network pharmacology predicts that "QN" agarwood modulates the epidermal growth factor receptor (EGFR) signaling pathway. "QN" agarwood can increase the expression of LC3B and Nphs1 in DKD mice while reducing the expression of EGFR. CONCLUSION: The present study demonstrated that "QN" agarwood ameliorated renal injury in DKD by targeting EGFR and restoring podocyte autophagy.

15.
Front Oncol ; 14: 1313548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500658

RESUMO

Background: Primary appendiceal tumors are rare. Low-grade appendiceal mucinous neoplasia (LAMN) and goblet cell adenocarcinoma (GCA) account for 20% and 14% of primary appendiceal tumors, respectively. The coexistence of LAMN and GCA is an extremely rare event. This report presents a case of an elderly male patient with an appendiceal tumor composed of LAMN and GCA in the same appendix. Case presentation: A 72-year-old male patient was admitted to our institution presenting with a history of abdominal pain localized to the right lower quadrant for two months. Abdominal computed tomography (CT) showed a large dilated thickened cystic mass in the appendix, along with a small duodenal diverticulum. Laboratory tests indicated elevated levels of serum carcinoembryonic antigen (CEA) and cancer antigen 199 (CA19-9) markers. The patient underwent a laparoscopic right hemicolectomy and exploration of the duodenal diverticulum, and there was no finding of perforation of the duodenal diverticulum. Focal positivity for chromogranin A (CgA) and synaptophysin (Syn) was observed in the tumor cells of GCA. The final pathological diagnosis revealed the coexistence of LAMN staged pT4a and grade 1 GCA staged pT3 in the appendix. Unfortunately, the patient died due to severe septic shock and circulatory failure secondary to a perforated duodenal diverticulum. Conclusions: The coexistence of LAMN and GCA are extremely rare in the appendix and may result from the proliferation of two independent cellular lines. The coexistence of distinct neoplasms poses diagnostic and management challenges. Multidisciplinary team discussion may be essential in the effective management of these patients.

16.
Burns ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38503573

RESUMO

OBJECTIVE: Research indicates that long noncoding RNAs (lncRNAs) contribute significantly to fibrotic diseases. Although lncRNAs may play a role in hypertrophic scars after burns, its mechanisms remain poorly understood. METHODS: Using chip technology, we compared the lncRNA expression profiles of burn patients and healthy controls (HCs). Microarray results were examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) to verify their reliability. The biological functions of differentially expressed mRNAs and the relationships between genes and signaling pathways were investigated by Gene Ontology (GO) and pathway analyses, respectively. RESULTS: In contrast with HCs, it was found that 2738 lncRNAs (1628 upregulated) and 2166 mRNAs (1395 upregulated) were differentially expressed in hypertrophic scars after burn. Results from RT-PCR were consistent with those from microarray. GO and pathway analyses revealed that the differentially expressed mRNAs are mainly associated with processes related to cytokine secretion in the immune system, notch signaling, and MAPK signaling. CONCLUSION: The lncRNA expression profiles of hypertrophic scars after burn changed significantly compared with HCs. It was believed that the transcripts could be used as potential targets for inhibiting abnormal scar formation in burn patients.

17.
BMC Psychiatry ; 24(1): 229, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532354

RESUMO

PURPOSE: Conceptualizing adolescent NSSI and emotional symptoms as a system of causal elements could provide valuable insights into the development of non-suicidal self-injury (NSSI) in adolescent. This study aimed to explore the intricate relationship between NSSI, depressive symptoms, and anxious symptoms in adolescents, identifying key symptoms to establish a theoretical foundation for targeted and effective interventions addressing NSSI behaviors in this population. METHODS: A total of 412 adolescents with NSSI behaviors were selected from outpatients. Generalized anxious disorder scale (GAD-7) and patient health questionnaire (PHQ-9) were employed to measure anxious symptoms and depressive symptoms, respectively. The adolescent non-suicidal self-injury assessment questionnaire (ANSSIAQ) was used to evaluate NSSI of adolescent. Using network analysis, the NSSI、depressive symptoms and anxious symptoms network were constructed to identify the most central symptoms and the bridge symptoms within the networks. RESULTS: The findings revealed that the NSSI functional nodes "coping with sadness and disappointment" and "relieving stress or anxious" exhibited the strongest correlation, with a regularized partial correlation coefficient was 0.401. The symptoms "having a desire to harm oneself and unable to stop" and the node "depressive symptoms" had the highest strength centrality in the network, and their strength centrality indices were 1.267 and 1.263, respectively. The bridge nodes were "having a desire to harm oneself and unable to stop" and "expressing one's despair and hopelessness", with expected impact indices of 0.389 and 0.396, respectively. CONCLUSION: In adolescents, the network revealed a closer connection between NSSI and depressive symptoms. "The desire to not stop hurting oneself" is not only broadly connected to other nodes but also could activate other nodes to maintain NSSI behavior. In light of these findings, precise targets for pharmacological treatment, psychotherapy, physical therapy, etc., are identified for adolescents with NSSI. Targeting this specific aspect in interventions may contribute to preventing and reducing NSSI behavior in adolescents.


Assuntos
Comportamento Autodestrutivo , Humanos , Adolescente , Comportamento Autodestrutivo/psicologia , Afeto , Inquéritos e Questionários , Ansiedade , Emoções
18.
Liver Int ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554043

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, can inhibit the growth of various tumours in vitro and in vivo. However, it remains unclear whether aprepitant has cytotoxic effects on iCCA. METHODS: We measured the expression of SP/NK-1R in clinical samples of iCCA by immunohistochemistry. Then, we detected the cytotoxic effects of aprepitant on iCCA cells via MTT, EdU and colony formation assay. We constructed a subcutaneous xenograft model of BALB/c nude mice by using HCCC-9810 and RBE cell lines to explore the effects of aprepitant in vivo. To elucidate the potential mechanisms, we explored the pro-apoptotic effect of aprepitant by flow cytometric, western blotting, ROS detection and JC-1 staining. Furthermore, we detected the autophagic level of HCCC-9810 and RBE by western blotting, mRFP-eGFP-LC3 adenovirus transfection and electron microscope. RESULTS: SP/NK-1R is significantly expressed in iCCA. Aprepitant inhibited human iCCA xenograft growth and dose-dependently decreased the viability of RBE and HCCC-9810 cells. Aprepitant-induced mitochondria-dependent apoptosis through ROS/JNK pathway. Additionally, pretreatment with z-VAD-fmk partly reversed the effect of aprepitant on cell viability, while NAC completely attenuated the cytotoxic effects of aprepitant in vitro. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC-9810 cells treated with aprepitant. CONCLUSION: SP/NK-1R signalling is significantly activated in iCCA and promotes the proliferation of iCCA cells. By contrast, aprepitant can induce autophagy and apoptosis in iCCA cells via ROS accumulation and subsequent activation of JNK.

19.
Cell Death Dis ; 15(3): 209, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480704

RESUMO

Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.


Assuntos
L-Lactato Desidrogenase , Proteômica , Humanos , Animais , Camundongos , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5/metabolismo , Linhagem Celular Tumoral , Glicólise , Lactatos , Tolerância a Radiação/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...