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This paper presents the findings of an observational study involving 38 patients to evaluate the application of a surgical technique utilizing an autologous costal cartilage scaffold for correcting nasal tip and alar asymmetry in unilateral cleft lip-nasal deformity. Nasal septum extension spreader grafts (SEG) and warped alar batten grafts, both made from autologous costal cartilage, were utilized in open rhinoplasty procedures. The warped alar batten graft was fixed to the caudal end of the SEG, with the lower lateral cartilage on the cleft side suspended to the free part of the newly created warped alar batten graft to lift the collapsed nasal alar further. Measurements of nasal tip height, nostril height, and the intersection angle of the nasal sill and alar (α) were taken before and after surgery, comparing the ratios between the normal and cleft sides. Patients were followed up for 2.5 to 5.5 years, with all cases showing successful healing and no complications. Postoperative improvements in nasal tip and nostril asymmetries were significant, with statistically significant changes observed in nasal tip height, nostril height, and the intersection angle of nasal sill and alar (α) (P<0.05). The combined use of SEG and warped alar batten graft, both crafted from autologous costal cartilage, effectively corrected nasal tip and alar asymmetry in adult cleft lip nasal deformity cases.
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Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic â¢OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.
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Ferroptose , Glucose Oxidase , Indóis , Compostos de Manganês , Nanopartículas , Óxidos , Terapia Fototérmica , Polímeros , Terapia Fototérmica/métodos , Compostos de Manganês/química , Animais , Humanos , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Indóis/química , Polímeros/química , Glucose Oxidase/metabolismo , Glucose Oxidase/administração & dosagem , Nanopartículas/química , Camundongos , Óxidos/química , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos BALB C , Terapia Combinada/métodos , Feminino , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Camundongos NusRESUMO
OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.
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Pancreatite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Pancreatite/etiologia , Pancreatite/epidemiologia , Pancreatite/complicações , Estudos Retrospectivos , Adulto , Estudos de Casos e Controles , Prevalência , Resultado do Tratamento , Idoso , Doença Aguda , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Doenças Vasculares/etiologia , Doenças Vasculares/epidemiologiaRESUMO
OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.
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Antibacterianos , Metanálise em Rede , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Mupirocina/uso terapêutico , Mupirocina/administração & dosagemRESUMO
BACKGROUND: The tumor immune microenvironment (TIME) is an important regulator of tumor progression, growth and metastasis. In addition, tumor metastasis is one of the principal obstacles to the treatment of colorectal cancer (CRC). Circular RNAs (circRNAs) have been recognized as important regulators in the development of malignancies. However, their specific roles and mechanisms in both CRC metastasis and TIME have not been thoroughly investigated. METHODS: High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were performed to identify differential circRNAs in CRC. Functional assays including transwell assay, wound healing assay, and metastasis models were conducted to assess the effect of circRNF216 on CRC metastasis. In addition, luciferase reporter, western blot, RNA immunoprecipitation (RIP), and fluorescent in situ hybridization (FISH) were performed to explore the underlying mechanism of circRNF216. The level of immune infiltration was assessed by bioinformatics analysis and flow cytometry in CRC model. Furthermore, rescue and mutation experiments were used for verification. RESULTS: circRNF216 was identified as a putative tumor suppressor that is downregulated in CRC tissues and cells. Overexpression of circRNF216 inhibits metastasis in vitro and vivo. Mechanistically, circRNF216 acts as a competitive endogenous RNA (ceRNA) for miR-576-5p, alleviating miR-576-5p repression on its target ZC3H12C, which in turn downregulated N-cadherin. Additionally, circRNF216 could enhance the infiltration level of CD8+ T cells by upregulating ZC3H12C, ultimately inhibiting the development of CRC, which suggests that circRNF216 is a potential biomarker for the treatment of CRC. CONCLUSIONS: Here, we provide novel mechanistic insight revealing how circRNF216 functioned in CRC metastasis and TIME via the circRNF216/miR-576-5p/ZC3H12C pathway. Therefore, circRNF216 holds promise as a potential therapeutic target and novel diagnostic marker for CRC.
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Neoplasias Colorretais , MicroRNAs , Humanos , Linfócitos T CD8-Positivos , Hibridização in Situ Fluorescente , RNA Circular/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Adulto , Papillomavirus Humano , Estudos de Coortes , Estudos Prospectivos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecções por Papillomavirus/tratamento farmacológico , Papillomaviridae , GenótipoRESUMO
OBJECTIVE: This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury (SCI) in the central nervous system (CNS) and its mechanism in promoting the structural and functional recovery of the injured CNS. METHODS: A compressive SCI mouse model was utilized for this investigation. Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein, acrolein-induced inflammation-related factors, and macrophages at the injury site and within the CNS. Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase (PI3K)/AKT pathway to study macrophage regulation. The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67 (GAD65/67), vesicular glutamate transporter 1 (VGLUT1), paw withdrawal response, and Basso Mouse Scale score. Nissl staining and Luxol Fast Blue (LFB) staining were performed to investigate the structural recovery of the injured CNS. RESULTS: Hydralazine downregulated the levels of acrolein, IL-1ß, and TNF-α in the spinal cord. The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway, leading to M2 macrophage polarization, which protected neurons against SCI-induced inflammation. Additionally, hydralazine promoted the structural recovery of the injured spinal cord area. Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression. Furthermore, hydralazine facilitated motor function recovery following SCI. Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS. CONCLUSION: Hydralazine, an acrolein scavenger, significantly mitigated SCI-induced inflammation and oxidative stress in vivo, modulated macrophage activation, and consequently promoted the structural and functional recovery of the injured CNS.
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Neuralgia , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Acroleína/metabolismo , Acroleína/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Hidralazina/farmacologia , Neuralgia/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo , Macrófagos/metabolismoRESUMO
BACKGROUND: The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). METHODS: We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. RESULTS: The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. CONCLUSIONS: The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.
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Neoplasias Colorretais , Iodo , Trombose , Humanos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/cirurgia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/cirurgiaRESUMO
Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.
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Hipertermia Induzida , Neoplasias Nasofaríngeas , Pró-Fármacos , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Poliésteres , MamíferosRESUMO
Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.
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Ácido Hialurônico , Nanopartículas , Espécies Reativas de Oxigênio , Ácido Hialurônico/química , Doxorrubicina/química , Simulação de Dinâmica Molecular , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Receptores de Hialuronatos , Linhagem Celular TumoralRESUMO
Spinal cord injury (SCI) results in severe motor and sensory dysfunction with no effective therapy. Spinal cord debris (sp) from injured spinal cord evokes secondary SCI continuously. We and other researchers have previously clarified that it is mainly bone marrow derived macrophages (BMDMs) infiltrating in the lesion epicenter to clear sp, rather than local microglia. Unfortunately, the pro-inflammatory phenotype of these infiltrating BMDMs is predominant which impairs wound healing. Hydralazine, as a potent vasodilator and scavenger of acrolein, has protective effects in many diseases. Hydralazine is also confirmed to promote motor function and hypersensitivity in SCI rats through scavenging acrolein. However, few studies have explored the effects of hydralazine on immunomodulation, as well as spontaneous pain and emotional response, the important syndromes in clinical patients. It remains unclear whether hydralazine affects infiltrating BMDMs after SCI. In this study, we targeted BMDMs to explore the influence of hydralazine on immune cells in a mouse model of SCI, and also investigated the contribution of polarized BMDMs to hydralazine-induced neurological function recovery after SCI in male mice. The adult male mice underwent T10 spinal cord compression. The results showed that in addition to improving motor function and hypersensitivity, hydralazine relieved SCI-induced spontaneous pain and emotional response, which is a newly discovered function of hydralazine. Hydralazine inhibited the recruitments of pro-inflammatory BMDMs and educated infiltrated BMDMs to a more reparative phenotype involving in multiple biological processes associated with SCI pathology, including immune/inflammation response, neurogenesis, lipid metabolism, oxidative stress, fibrosis formation, and angiogenesis, etc. As an overall effect, hydralazine-treated BMDMs loaden with sp partially rescued neurological function after SCI. It is concluded that hydralazine plays an immunomodulation role of educating pro-inflammatory BMDMs to a more reparative phenotype; and hydralazine-educated BMDMs contribute to hydralazine-induced improvement of neurological function in SCI mice, which provides support for drug and cell treatment options for SCI therapy.
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Acroleína , Traumatismos da Medula Espinal , Ratos , Camundongos , Masculino , Animais , Acroleína/metabolismo , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Macrófagos/metabolismo , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Hidralazina/metabolismo , Medula Espinal/patologia , Dor/metabolismoRESUMO
Cardiac paragangliomas (PGLs) are rare neuroendocrine tumors, and data regarding the features of nonfunctioning PGLs are limited. These tumors are extensively vascularized and have high risk of hemorrhage for surgery and even biopsy. Differential diagnosis including biochemical analysis of these PGLs is important for further management. In this case report, we present the clinical, laboratory, imaging, and radionuclide presentations of a rare primary nonfunctioning cardiac PGL with a coronary aneurysm. Echocardiography initially showed a large echogenic mass in the left atrioventricular groove. The mass presented a diffuse hyperenhancement pattern with a central perfusion defect on contrast echocardiography. The tumor enclosed the left coronary artery from the coronary orifice, and an aneurysm was found in the left circumflex artery, with significantly increased flow velocity. These echocardiographic features and its susceptible location are indicative of the presence of a cardiac PGL. Although all biochemical evaluations of catecholamines from blood and urine samples were negative, positron emission tomography and scintigraphy finally confirmed the diagnosis of a primary cardiac PGL. Therefore, when imaging features are indicative of the presence of PGLs, the implementation of radionuclide imaging for final diagnosis is required even if the biochemical results are negative. Recognizing these uncommon Doppler and contrast echocardiographic characteristics is important for early diagnosing these nonfunctioning PGLs.
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Aneurisma Coronário , Paraganglioma , Humanos , Ecocardiografia , Paraganglioma/diagnóstico por imagem , Catecolaminas , Vasos Coronários/patologiaRESUMO
BACKGROUND: Most cases of extrahepatic cholangiocarcinoma (ECC) show various degrees of hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC). However, the factors influencing ADC values in ECC have not yet been explored extensively. Therefore, this study explored the independent factors influencing ADC values in ECC. METHODS: A total of 88 patients with ECC confirmed by surgical pathology were retrospectively assessed. All patients underwent abdominal magnetic resonance imaging (MRI) at 3.0 T and ADC values of the tumor were measured. The correlation between ADC values and multiple clinicopathological features in ECC was analyzed, and independent factors influencing the ADC values in ECC were explored further. RESULTS: The ADC value of the tumor showed a significant difference in different perineural invasion group (p = 0.048), microvascular invasion group (p = 0.001), vascular endothelial growth factor expression group (p < 0.001), lymphatic status group (p = 0.003), and differentiation degree (DD) group (p < 0.001). However, there were no significant differences in different sex (p = 0.715), tumor location (p = 0.659), and degree of T stage (p = 0.879). Moreover, ADC value was negatively correlated with microvascular density (r = -0.725, p < 0.001) and lesion size (r = -0.244, p = 0.023). Nevertheless, there was no correlation between ADC value and patient age (r = 0.026, p = 0.812). Further regression analysis indicated that ADC value was independently associated with pathological DD of ECC (R2 = 0.678, p < 0.001) but not with other clinicopathological factors (p > 0.05). CONCLUSION: ADC value of ECC is independently correlated with pathological DD of ECC, indicating that ADC value is a potential imaging biomarker for predicting the degree of ECC malignancy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular , Colangiocarcinoma/diagnóstico por imagem , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-HepáticosRESUMO
RNA-binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review.
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Proteínas e Peptídeos de Choque Frio , Hipotermia , Proteínas e Peptídeos de Choque Frio/genética , Proteínas e Peptídeos de Choque Frio/metabolismo , Temperatura Baixa , Resposta ao Choque Frio , Humanos , Hipotermia/metabolismo , Neuroproteção , Proteínas de Ligação a RNA/metabolismoRESUMO
Caspases are a family of evolutionary conserved cysteine proteases that play key roles in programmed cell death and inflammation. Among the methods for the detection of caspase activity, biosensors based on luciferases have advantages in genetical encoding and convenience in assay. In this study, we constructed a new set of caspase biosensors based on NanoLuc luciferase. This kind of sensors, named NanoLock, work in dark-to-bright model, with the help of a NanoLuc quencher peptide (HiBiT-R/D) mutated from HiBiT. Optimized NanoLock responded to proteases with high signal to noise ratio (S/N), 1233-fold activation by tobacco etch virus protease in HEK293 cells and > 500-fold induction to caspase 3 in vitro. We constructed NanoLocks for the detection of caspase 1, 3, 6, 7, 8, 9, and 10, and assays in HEK293 cells demonstrated that these sensors performed better than commercial kits in the aspect of S/N and convenience. We further established a cell line stably expressing NanoLock-casp 6 and provided a proof-of-concept for the usage of this cell line in the high throughput screening of caspase 6 modulator.
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Apoptose , Caspases , Caspase 3 , Caspases/genética , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismoRESUMO
O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the "optimal zone", and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.
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Complicações do Diabetes , Resistência à Insulina , Complicações do Diabetes/metabolismo , Glicosilação , Humanos , Contração Muscular , Músculo Esquelético/metabolismoRESUMO
Background: Safety concerns are one of the most common reasons for COVID-19 vaccination refusal. In the field of plastic and reconstructive surgery, whether COVID-19 vaccination influences wound healing and scar formation is worthy of special attention. Methods: In this study, patients with adult trauma with subcutaneous sutures placed by a single plastic surgeon in a single center were included. The vaccination interval was defined as the interval between the last dose of the COVID-19 vaccine and when surgical sutures were introduced. The patients were categorized by vaccination interval into three groups of <1, 1-3, and ≥3 months. Wound healing and scar formation were rated according to the Wound Assessment Inventory (WAI) and Patient and Observer Scar Assessment Scale (POSAS) in the groups at 7 days and after a 3-month follow-up. Results: All total and individual scores of WAI and POSAS were not significantly different among the groups. Conclusion: No differences in wound healing and scar formation were observed in patients with different COVID-19 vaccination intervals. Thus, it is not necessary to postpone COVID-19 vaccination, as the vaccine does not affect wound healing and scar formation in patients undergoing surgery. This study aimed to eliminate concerns and hesitancy in receiving the COVID-19 vaccine.
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COVID-19 , Cicatriz , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Cicatriz/patologia , Cicatriz/prevenção & controle , Humanos , Vacinação , CicatrizaçãoRESUMO
Colorectal cancer (CRC) remains a heavy health burden worldwide. Transketolase (TKT) is a crucial enzyme in the non-oxidative phase of the Pentose Phosphate Pathway (PPP), and is up-regulated in multiple cancer types. However, the role of TKT in the prognosis of CRC remains unclear. We aimed to explore whether TKT expression is altered in CRC, how TKT is associated with the prognosis of CRC, and whether the regulation of TKT might have an impact on CRC. Differentially expressed genes (DEGs) were identified using bioinformatics analysis. TKT expression was examined in the human colon adenocarcinoma tissue microarray and xenografts. Cell viability, proliferation, migration, and apoptosis assays in vitro were applied to evaluate the protumoral effects of TKT on CRC. TKT was found to be a risk factor for the poor prognosis of CRC by bioinformatics analysis among the DEGs. TKT was significantly up-regulated in colon adenocarcinoma tissues compared with normal colon tissues in patients. Moreover, similar results were found in HCT116 and RKO human colon adenocarcinoma xenografts in nude mice. TKT expression was positively associated with advanced TNM stage, positive lymph nodes, and poor 5 or 10-year overall survival of CRC patients. In vitro, inhibition of TKT reduced cell viability, proliferation, and migration, and induced cell apoptosis. In addition, inhibition of TKT decreased the protein levels of NICD and Hes1. In conclusion, high TKT expression was associated with the poor prognosis of CRC patients. The protumoral effects of downregulating TKT may be realized by suppressing the Notch signaling pathway. TKT may be a new prognostic biomarker and therapeutic target for CRC.
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Herein we present a case of hypereosinophilic syndrome (HES) with recurrent involvement of mitral valve. The patient developed mitral regurgitation secondary to HES. Surgical mitral valve replacement was performed successfully. The prosthetic valve dysfunction occurred 3 years later and echocardiography showed severe mitral valve stenosis. Extensive mural thrombi were discovered on both sides of the stenotic valve with eosinophilic infiltration. The patient underwent a repeated mechanical prosthesis replacement and recovered uneventfully.
Assuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Síndrome Hipereosinofílica , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Trombose , Humanos , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/diagnóstico por imagem , Trombose/complicaçõesRESUMO
OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.