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BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.
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Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Invasividade Neoplásica , Complexo Repressor Polycomb 2 , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Movimento Celular/genética , Prognóstico , Linhagem Celular Tumoral , Feminino , Masculino , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Técnicas de Silenciamento de GenesRESUMO
BACKGROUND: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. METHODS: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH). RESULTS: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. CONCLUSION: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.
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Fibroblastos , MicroRNAs , Fibrose Oral Submucosa , RNA Circular , Proteína 3 Supressora da Sinalização de Citocinas , Humanos , MicroRNAs/metabolismo , Fibrose Oral Submucosa/patologia , Fibrose Oral Submucosa/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Fibroblastos/metabolismo , RNA Circular/genética , Miofibroblastos , Masculino , Movimento Celular , Mucosa Bucal/metabolismo , Mucosa Bucal/citologia , Mucosa Bucal/patologia , Transdução de Sinais , Feminino , Células CultivadasRESUMO
BACKGROUND: Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LETd), despite high CIRT dose. PURPOSE: This study aimed to investigate the approaches to up-modulate the CIRT LETd and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. METHODS: 10 LAPCs that had been irradiated by CIRT with 67.5 Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LETd and OER investigations. Our considerations for up-modulating LETd were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LETd could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks. The LETd and the corresponding OER distributions of each type of SIB plan were evaluated. RESULTS: We delivered up to 100 Gy (RBE) to GTVcore using SIB. The mean LETd of GTV increased significantly by 21.3% from 47.8 to 58.0 keV/µm (p < 0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p < 0.05). The GI LETdS in all modulated plans were not more than those in the original plans. CONCLUSIONS: SIB could effectively increase CIRT LETd to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.
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Radioterapia com Íons Pesados , Transferência Linear de Energia , Neoplasias Pancreáticas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Neoplasias Pancreáticas/radioterapia , Humanos , Radioterapia com Íons Pesados/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação , PrognósticoRESUMO
This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.
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Carcinoma Hepatocelular , Radioterapia com Íons Pesados , Neoplasias Hepáticas , Lesões por Radiação , Humanos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Dosagem Radioterapêutica , Radioterapia com Íons Pesados/métodosRESUMO
OBJECTIVE: The objective of this investigation was to examine the presence of interleukin (IL)-13 and its receptor IL-13Rα2 in the tissues of oral submucous fibrosis (OSF), investigate their biological functions, and explore the underlying mechanisms involved in the development of OSF. MATERIALS AND METHODS: The expression of IL-13 and IL-13Rα2 in the oral mucosa of patients with OSF and normal individuals was determined through immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary fibroblasts (FBs) were extracted through enzymatic digestion and then cultured. Immunofluorescence was employed to identify the FB cultures and the location of IL-13Rα2. The effects of IL-13/IL-13Rα2/PI3K/AKT/mTOR on the migration, proliferation, and secretion of fiber-related proteins of FBs were explored via the wound healing assay, CCK-8 assay, EDU assay, and RT-qPCR. The impact of IL-13Rα2 silencing and PI3K/AKT inhibition on the effect of IL-13 on FBs was analyzed by RT-qPCR and Western blotting. RESULTS: IL-13 and IL-13Rα2 were highly expressed in OSF. Primary FBs were successfully extracted and cultured. IL-13Rα2 was found to be localized in myofibroblasts. IL-13 promoted the proliferation, migration, and secretion of fibril-associated proteins in FBs. The proliferation, migration, and secretion of fibril-associated proteins of FBs were decreased following IL-13Rα2 silencing and inhibition of the PI3K/AKT/mTOR pathway. CONCLUSION: IL-13 may promote the proliferation, migration, and secretion of fiber-related proteins of FBs through the PI3K/AKT/mTOR pathway by targeting IL-13Rα2.
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The precise detection of stratum interfaces holds significant importance in geological discontinuity recognition and roadway support optimization. In this study, the model for locating rock interfaces through change point detection was proposed, and a drilling test on composite strength mortar specimens was conducted. With the logistic function and the particle swarm optimization algorithm, the drilling specific energy was modulated to detect the stratum interface. The results indicate that the drilling specific energy after the modulation of the logistic function showed a good anti-interference quality under stable drilling and sensitivity under interface drilling, and its average recognition error was 2.83 mm, which was lower than the error of 6.56 mm before modulation. The particle swarm optimization algorithm facilitated the adaptive matching of drive parameters to drilling data features, yielding a substantial 50.88% decrease in the recognition error rate. This study contributes to enhancing the perception accuracy of stratum interfaces and eliminating the potential danger of roof collapse.
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The safety valves of powered supports control the maximum working resistance, and their statuses must be known to ensure the safety of both the support and the overlying strata. However, the inspection of powered support valves involves manual or semiautomated operations, the costs of which are high. In this study, an extreme point extraction method was developed for the determination of the characteristic parameters of safety valves using roof pressure data, and a safety valve state monitoring module was constructed. Using the longwall face of 0116306 with top coal caving in the Mindong Mine as an example, the characteristic parameters of the safety valves were extracted, including the peak, reseating, and blowdown pressures, as well as the recovery and unloading durations. The results of the field tests showed the following: (1) The amplitude threshold method based on extreme points can be used to accurately extract characteristic parameters, and the distribution of the characteristic parameters of the safety valves follows either a Gaussian or an exponential distribution. (2) The mining pressure analysis results, derived from the characteristic parameters, closely align with the in situ mining pressure observations. This method can be used for the online monitoring of safety valve conditions, increasing the operational efficiency and quality of safety valve inspections.
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BACKGROUND: The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. METHODS: IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. RESULTS: We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. CONCLUSIONS: Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação para Baixo , Proteína 7 com Repetições F-Box-WD/metabolismo , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Proteína 7 com Repetições F-Box-WD/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Transplante de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Estabilidade de RNA , Análise de Sequência de RNARESUMO
PURPOSE: To develop and validate a clinico-biological features and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) radiomic-based nomogram via machine learning for the pretherapy prediction of discriminating between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in non-small cell lung cancer (NSCLC). METHODS: A total of 315 NSCLC patients confirmed by postoperative pathology between January 2017 and June 2019 were retrospectively analyzed and randomly divided into the training (n = 220) and validation (n = 95) sets. Preoperative clinical factors, serum tumor markers, and PET, and CT radiomic features were analyzed. Prediction models were developed using the least absolute shrinkage and selection operator (LASSO) regression analysis. The performance of the models was evaluated and compared by the area under receiver-operator characteristic (ROC) curve (AUC) and DeLong test. The clinical utility of the models was determined via decision curve analysis (DCA). Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: In total, 122 SCC and 193 ADC patients were enrolled in this study. Four independent prediction models were separately developed to differentiate SCC from ADC using clinical factors-tumor markers, PET radiomics, CT radiomics, and their combination. The DeLong test and DCA showed that the Combined Model, consisting of 2 clinical factors, 2 tumor markers, 7 PET radiomics, and 3 CT radiomic parameters, held the highest predictive efficiency and clinical utility in predicting the NSCLC subtypes compared with the use of these parameters alone in both the training and validation sets (AUCs (95% CIs) = 0.932 (0.900-0.964), 0.901 (0.840-0.957), respectively) (p < 0.05). A quantitative nomogram was subsequently constructed using the independently risk factors from the Combined Model. The calibration curves indicated a good consistency between the actual observations and nomogram predictions. CONCLUSION: This study presents an integrated clinico-biologico-radiological nomogram that can be accurately and noninvasively used for the individualized differentiation SCC from ADC in NSCLC, thereby assisting in clinical decision making for precision treatment.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Aprendizado de Máquina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos RetrospectivosRESUMO
BACKGROUND: The purpose of this study was to investigate the value of 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) in tailoring axillary surgery by predicting nodal response among patients with node-positive breast cancer after neoadjuvant chemotherapy (NAC). METHODS: One hundred thirty-three patients with breast cancer with biopsy-confirmed nodal metastasis were prospectively enrolled. 18 F-FDG PET/CT scan was performed before NAC (a second one after two cycles with baseline maximum standardized uptake value [SUVmax ] ≥2.5), and a subset of patients underwent targeted axillary dissection (TAD). All the patients underwent axillary lymph node dissection (ALND). The accuracy was calculated by a comparison with the final pathologic results. RESULTS: With the cutoff value of 2.5 for baseline SUVmax and 78.4% for change in SUVmax , sequential 18 F-FDG PET/CT scans demonstrated a sensitivity of 79.0% and specificity of 71.4% in predicting axillary pathologic complete response with an area under curve (AUC) of 0.75 (95% confidence interval, 0.65-0.84). Explorative subgroup analyses indicated little value for estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive patients (AUC, 0.55; sensitivity, 56.5%; specificity, 50.0%). Application of 18 F-FDG PET/CT could spare 19 patients from supplementary ALNDs and reduce one of three false-negative cases in TAD among the remaining patients without ER-negative/HER2-positive subtype. CONCLUSION: Application of the subtype-guided 18 F-FDG PET/CT could accurately predict nodal response and aid in tailoring axillary surgery among patients with node-positive breast cancer after NAC, which includes identifying candidates appropriate for TAD or directly proceeding to ALND. This approach might help to avoid false-negative events in TAD. IMPLICATIONS FOR PRACTICE: This feasibility study showed that 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) could accurately predict nodal response after neoadjuvant chemotherapy (NAC) among patients with breast cancer with initial nodal metastasis except in estrogen receptor-negative, human epidermal growth factor receptor 2-positive subtype. Furthermore, the incorporation of 18 F-FDG PET/CT can tailor subsequent axillary surgery by identifying patients with residual nodal disease, thus sparing those patients supplementary axillary lymph node dissection. Finally, we have proposed a possibly feasible flowchart involving 18 F-FDG PET/CT that might be applied in post-NAC axillary evaluation.
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Neoplasias da Mama , Fluordesoxiglucose F18 , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
Circular RNAs (circRNAs) are a novel class of non-coding RNAs which play important roles in human diseases and tumor progression. However, the function of circRNAs in ovarian cancer remains to be uncovered. Here we found a large amount of circRNAs that are differentially expressed in ovarian cancer tissues compared with normal ovarian tissues. We further identified one circRNA derived from the LPAR3 gene and termed Circ0004390, which was frequently upregulated in ovarian cancer tissues. The knockdown of Circ0004390 can significantly reduce the proliferation of ovarian cancer cells. We further demonstrated that Circ0004390 may promote cell proliferation by acting as a sponge for the miR-198 family to regulated the MET expression in ovarian cancer cells. The level of Circ0004390 was closely related with overall survival of ovarian cancer patients. Our findings suggested that Circ0004390 regulated ovarian cancer proliferation by miR-198/MET axis, which might provide a potential target for the treatment of ovarian cancer.
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MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Circular/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , RNA Circular/genéticaRESUMO
Ahead of Print article withdrawn by publisher.
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Therapy-related side effects and severe antimicrobial resistance still remain an obstacle to Helicobacter pylori eradication. This meta-analysis aimed to investigate the efficacy of Lactobacillus-supplemented triple therapy on H. pylori eradication rates and therapy-related side effects in children. Five studies involving 484 pediatric patients were included in our analysis. The pooled relative risk (RR) for eradication rates in the Lactobacillus group versus the control group was 1.19 [95% confidence interval (CI) 1.07-1.33]. In subgroup analyses based on dose and duration of Lactobacillus supplementation, the pooled RRs for eradication rates were 1.36 (95% CI 1.15-1.60) in the high-dose group, 1.08 (95% CI 0.86-1.35) in the low-dose group, 1.24 (95% CI 1.06-1.46) in the long-term group, and 1.17 (95% CI 0.96-1.44) in the short-term group. With respect to side effects, Lactobacillus supplementation significantly reduced the incidence of diarrhea (RR = 0.30, 95% CI 0.10-0.85).Conclusions: Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children. And a higher dose and a longer duration of supplementation may conduce to the positive impact of Lactobacillus on H. pylori eradication. What is Known: ⢠Probiotics-supplemented triple therapy may be beneficial in improving H. pylori eradication rates and reducing therapy-related side effects in children. However, not all probiotics are beneficial to H. pylori eradication and the pooled outcomes based on different probiotics may be erroneously extrapolated to other ineffective strains. What is New: ⢠Lactobacillus, as an adjunct to triple therapy, can increase H. pylori eradication rates as well as reduce the incidence of therapy-related diarrhea in children.
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Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Lactobacillus , Probióticos/uso terapêutico , Adolescente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Suplementos Nutricionais , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We therefore investigated the effect of cannabinoids on retinal capillaries and pericytes. METHODS: The effects of cannabinoids on capillary diameters were determined using an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to explore the underlying mechanism. RESULTS: Endogenous cannabinoid 2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated the noradrenaline-precontracted capillaries in a concentration-dependent manner (1 µM to 0.1 mM). The extent of vasorelaxation was positively correlated with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation and pericyte width were inhibited by a cannabinoid receptor type-1 (CB1) antagonist, AM251 or rimonabant (SR141716A), the nitric oxide synthase inhibitor l-NAME, and the guanylate cyclase inhibitor ODQ. They were also abolished by the removal of the endothelium, but not by the cannabinoid receptor-2 antagonist SR144528, the endothelial cannabinoid receptor antagonist O-1918, or the cyclooxygenase inhibitor indomethacin. CONCLUSION: The exogenous cannabinoid R-(+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB1 and the nitric oxide-cyclic guanosine monophosphate pathway, and requires an intact endothelium.
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Canabinoides/farmacologia , Capilares/efeitos dos fármacos , Pericitos/citologia , Pericitos/efeitos dos fármacos , Retina/citologia , Animais , Ácidos Araquidônicos/farmacologia , Western Blotting , Canfanos/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Imuno-Histoquímica , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptores de Canabinoides/metabolismo , Retina/efeitos dos fármacos , RimonabantoRESUMO
OBJECTIVE: To study the distribution of peak intraocular pressure (IOP) in 24-hour in untreated primary open angle glaucoma (POAG) patients, and to explore the correlation between nocturnal peak IOP and office hour or diurnal IOP level. METHODS: A Cross-sectional study.One hundred and twenty-one untreated POAG patients (121 eyes), including 78 normal tension patients (78 eyes) and 43 hyper-tension patients (43 eyes), were enrolled in this study. All the patients underwent 24-hour IOP monitoring with non-contact tonometer. The distribution of peak IOP in 24-hour and the correlation between nocturnal peak IOP and office hour or diurnal mean and peak IOP were evaluated. Categorical variables were described as frequency and constituent ratio, and analyzed by chi-square test. Continuous variables were described as mean, standard deviation, range, and analyzed by independent samples t test, pearson correlation test and linear regression. RESULTS: In all glaucoma patients, peak IOP occurred mainly from 8:00 to 10:00 and 8:00 to 10:00.In normal tension group, peak IOP appeared mainly from 8:00 to 10:00 and from 0:00 to 6:00, the highest frequency showed at 8:00 (17 eyes 18.48%).In hyper-tension group, the probability of IOP reaching peak was more in night time, mainly from 0:00 to 6:00, the highest frequency showed at 2:00 (10 eyes 21.28%). If only the peak IOP during office hours or diurnal hours were considered, then only 32.55% (14/43) and 44.19% (19/43) patients could be correctly diagnosed. The remaining patients would be missed because of low IOP and/or mild structure and/or functional damages. There were good linear correlations between office hours or diurnal peak and mean IOP and nocturnal peak IOP in glaucoma patients. CONCLUSIONS: More than 50% peak IOP occurred out of office hour in POAG patients. There is a good correlation between peak nocturnal IOP and office hour or diurnal IOP level.
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Ritmo Circadiano/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Pressão Intraocular/fisiologia , Estudos Transversais , Feminino , Glaucoma/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Masculino , Monitorização Fisiológica , Fatores de Tempo , Tonometria OcularRESUMO
BACKGROUND: Radical cystectomy (RC) is the standard treatment for patients with muscle-invasive bladder cancer (BC), and it is also a valid option for selected patients with high-risk non-muscle-invasive BC. The purpose of this study was to evaluate the effect on the lower skeletal muscle index (SMI) of short-term postoperative complications of radical cystectomy (RC) in patients with bladder cancer (BC). METHODS: A total of 247 patients who received RC for BC and 204 age-matched healthy population-based controls were retrospectively assessed. SMI was measured by preoperative computed tomography scans at the L4 to L5 level. Early complications were graded by Clavien-Dindo classification; severity of grade III or greater was identified as a severe complication. Logistic regression was utilized to determine the relationships between covariables and severe complications. RESULTS: A total of 125 (50.61%)/19 (7.69%) patients exhibited overall/severe complications during the early postoperative period. SMI was strongly associated with gender (P <0.01), but not age and body mass index (BMI), among patients with BC. Compared with the matched control group, BC patients exhibited lower SMI. The difference was statistically significant in the subgroup of male patients (P = 0.03). In the multivariate analysis, SMI was an independent predictor of developing severe complications. Each 1 cm²/m² increase in SMI was associated with a decrease in the odds of morbidity by 4.8%. CONCLUSIONS: A lower SMI is frequently observed in bladder cancer patients undergoing RC and is shown to be strongly associated with early complications following surgery.
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Cistectomia/efeitos adversos , Músculo Esquelético/patologia , Complicações Pós-Operatórias/etiologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
Background: Head and neck cancer is the 6th most common malignancy worldwide, and its incidence is still on the rise. The salvage surgery has been considered as an important treatment strategy for persistent or recurrent head and neck cancer. Therefore, we conducted a bibliometric analysis of salvage surgery for head and neck cancer since the 21st century. Methods: The literature about salvage surgery of head and neck cancer in Web of Science was searched. CiteSpace and VOSviewer were used to analyze main countries, institutions, authors, journals, subject hotspots, trends, frontiers, etc. Results: A total of 987 papers have been published since the 21st century. These publications were written by 705 authors from 425 institutions in 54 countries. The United States published 311 papers in this field and ranked first. Head & Neck was the most widely published journal. The main keyword clustering included terms such as #0 stereotactic radiotherapy (2012); #1 randomized multicenter (2007); #2 salvage surgery (2004); #3 functional outcomes (2014); #4 transoral robotic surgery (2013); #5 neck high-resolution computed tomography (2010); #6 complications (2008); #7 image guidance (2019). The current research frontiers that have been sustained are "recurrent", "risk factors", and "reirradiation". Conclusion: The current situation of the salvage surgery for head and neck cancer in clinical treatments and basic scientific research were summarized, providing new perspectives for the development of salvage surgery for head and neck cancer in the future.
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Cullin-RING ligase 4 (CRL4) has attracted enormous attentions because of its extensive regulatory roles in a wide variety of biological and pathological events, especially cancer-associated events. CRL4 exerts pleiotropic effects by targeting various substrates for proteasomal degradation or changes in activity through different internal compositions to regulate diverse events in cancer progression. In this review, we summarize the structure of CRL4 with manifold compositional modes and clarify the emerging functions and molecular mechanisms of CRL4 in a series of cancer-associated events.
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Background: Molecular glues, which reshape E3 ligase receptors to promote targeted protein degradation, are emerging as a promising therapeutic strategy, particularly in oncology, driven by rapidly advancing insights into their mechanisms and structural properties. Objective: This study aims to offer an insightful depiction and visualization of the knowledge structure, prevalent themes, and emerging trends within the domain since the year 2000, employing bibliometric analysis to achieve this goal. Methods: To conduct this research, a comprehensive collection of literature on molecular glues was sourced from the Web of Science database. Subsequently, the data underwent analysis utilizing CiteSpace and VOSviewer tools, enabling the identification of pivotal countries, institutions, authors, and journals, as well as the delineation of subject hotspots, trends, and the forefront of research in this evolving field. Result: Since 2000, 388 papers on molecular glues have been published, with a notable increase to an annual average of 43 articles post-2018. This research, contributed by 506 authors across 329 institutions, highlights the United States and China as leading nations in output, with 122 and 104 articles respectively. Takuzo Aida, Luc Brunsveld, and Christian Ottmann are identified as key authors. Nature emerges as the foremost publication venue, while the Chinese Academy of Sciences is the top contributing institution, underscoring the global engagement and interdisciplinary nature of molecular glue research. This study identified 19 distinct research clusters within the molecular glues domain. Conclusion: We reveal the current status, hotspots, and trends of molecular glue research since 2000, offering insights and novel scholarly perspectives on the field's prevailing limitations.