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The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.
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Edema Encefálico , Humanos , Edema Encefálico/etiología , Neurocirujanos , Estudios Retrospectivos , Edema/etiología , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Hemorragia CerebralRESUMEN
The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1ß, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.
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FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas , Animales , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Transducción de Señal , Enfermedades Neuroinflamatorias , Microglía/metabolismo , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ácido UrsólicoRESUMEN
High glucose (HG)-induced nucleotide-binding and oligomerization (NACHT) domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome activation leads to diabetic neuropathic pain. We recently showed that salidroside could suppress NLRP3 inflammasome activation in hepatocytes exposed to HG. The aim of this study was to evaluate the analgesic effect of salidroside on diabetic rats and to explore its underlying mechanisms. Rat models with diabetic neuropathic pain were induced by high-fat diet feeding combined with low dose streptozotocin injections. Doses of salidroside at 50 and 100 mg.kg-1.day-1 were administered by gavage to diabetic rats for 6 weeks. Mechanical allodynia test, thermal hyperalgesia test and biochemical analysis were performed to evaluate therapeutic effects. Primary dorsal root ganglion (DRG) cells exposed to HG at 45 mM were used to further study the effects of salidroside on the AMP-activated protein kinase (AMPK)-NLRP3 inflammasome axis and insulin sensitivity in vitro. Salidroside administration improved hyperglycemia, ameliorated insulin resistance, and alleviated neuropathic pain in diabetic rats. Moreover, salidroside induced AMPK activation and suppressed NLRP3 inflammasome activation in the DRGs of diabetic rats. In addition, salidroside treatment relieved oxidative stress, improved insulin sensitivity and regulated the AMPK-NLRP3 inflammasome axis in HG-treated DRGs in vitro. Furthermore, AMPK inhibition in vivo or AMPK silencing in vitro abolished the beneficial effects of salidroside on diabetic neuropathic pain. Together, these results indicate that salidroside alleviates diabetic neuropathic pain through its regulation of the AMPK-NLRP3 inflammasome axis in DRGs.
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Proteínas Quinasas Activadas por AMP/metabolismo , Analgésicos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neuropatías Diabéticas/prevención & control , Ganglios Espinales/efectos de los fármacos , Glucósidos/farmacología , Hipoglucemiantes/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neuralgia/prevención & control , Fenoles/farmacología , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/enzimología , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/fisiopatología , Ganglios Espinales/enzimología , Ganglios Espinales/fisiopatología , Resistencia a la Insulina , Masculino , Neuralgia/enzimología , Neuralgia/etiología , Neuralgia/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
BACKGROUND: Sterol regulatory-element binding proteins (SREBPs) and mir-33 (miR-33a, miR-33b), which are encoded by the introns of SREBPs, are key factors in the lipid metabolism pathway. SREBPs mRNA in circulating leucocyte and carotid plaques, along with various risk factors that associated with Coronary Atherosclerotic Disease (CAD) were investigated in a central Chinese cohort. METHODS: A total of 218 coronary atherosclerotic disease (CAD) patients, and 178 non-CAD controls, were recruited to collect leukocytes. Carotid plaques and peripheral blood were obtained from CAD patients undergoing carotid endarterectomy (CEA) (n = 12) while THP-1 and peripheral blood mononuclear cells (PBMCs) were stimulated with Oxidized low-density lipoprotein (ox-LDL) to establish an in vitro foam cell formation model. SREBPs and miR-33 levels were quantified by qPCR. Routine biochemical markers were measured using standard procedures. RESULTS: SREBP-1 mRNA level of circulating leucocytes in CAD patients were significantly lower than in non-CAD controls (p = 0.005). After stratification coronary artery atherosclerotic complexity, we detected a significant reduction of SREBP-1 in high-risk complexity CAD patients (SYNTAX score > 23) (p = 0.001). Logistic regression analysis indicated that decreased expression of SREBP-1 was a risk factor of CAD (odds ratio (OR) =0.48, 95% confidence interval (CI) = 0.30~0.76, p = 0.002) after adjusting clinical confounders; the mRNA levels of SREBPs in carotid plaques correlated with the corresponding value in circulating leukocytes (SREBP-1 r = 0.717, p = 0.010; SREBP-2 r = 0.612, p = 0.034). Finally, there was no significant difference in serum miR-33 levels between CAD patients and controls. CONCLUSIONS: Our finding suggesting a potential role in the adjustment of established CAD risk. The future clarification of how SREBP-1 influence the pathogenesis of CAD might pave the way for the development of novel therapeutic methods.
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Aterosclerosis/genética , Estenosis Carotídea/genética , Enfermedad de la Arteria Coronaria/genética , Leucocitos Mononucleares/metabolismo , MicroARNs/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Anciano , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/patología , Biomarcadores/sangre , Estenosis Carotídea/sangre , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/cirugía , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/patología , Endarterectomía Carotidea , Femenino , Regulación de la Expresión Génica , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/patología , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Lipoproteínas LDL/farmacología , Modelos Logísticos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Cultivo Primario de Células , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Riesgo , Transducción de Señal , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Células THP-1RESUMEN
BACKGROUND: Riboflavin, an intermediate of primary metabolism, is one kind of important food additive with high economic value. The microbial cell factory Bacillus subtilis has already been proven to possess significant importance for the food industry and have become one of the most widely used riboflavin-producing strains. In the practical fermentation processes, a sharp decrease in riboflavin production is encountered along with a decrease in the dissolved oxygen (DO) tension. Influence of this oxygen availability on riboflavin biosynthesis through carbon central metabolic pathways in B. subtilis is unknown so far. Therefore the unveiled effective metabolic pathways were still an unaccomplished task till present research work. RESULTS: In this paper, the microscopic regulation mechanisms of B. subtilis grown under different dissolved oxygen tensions were studied by integrating 13C metabolic flux analysis, metabolomics and transcriptomics. It was revealed that the glucose metabolic flux through pentose phosphate (PP) pathway was lower as being confirmed by smaller pool sizes of metabolites in PP pathway and lower expression amount of ykgB at transcriptional level. The latter encodes 6-phosphogluconolactonase (6-PGL) under low DO tension. In response to low DO tension in broth, the glucose metabolic flux through Embden-Meyerhof-Parnas (EMP) pathway was higher and the gene, alsS, encoding for acetolactate synthase was significantly activated that may result due to lower ATP concentration and higher NADH/NAD+ ratio. Moreover, ResE, a membrane-anchored protein that is capable of oxygen regulated phosphorylase activity, and ResD, a regulatory protein that can be phosphorylated and dephosphorylated by ResE, were considered as DO tension sensor and transcriptional regulator respectively. CONCLUSIONS: This study shows that integration of transcriptomics, 13C metabolic flux analysis and metabolomics analysis provides a comprehensive understanding of biosynthesized riboflavin's regulatory mechanisms in B. subtilis grown under different dissolved oxygen tension conditions. The two-component system, ResD-ResE, was considered as the signal receiver of DO tension and gene regulator that led to differences between biomass and riboflavin production after triggering the shifts in gene expression, metabolic flux distributions and metabolite pool sizes.
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Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Oxígeno/metabolismo , Riboflavina/biosíntesis , Acetolactato Sintasa/genética , Acetolactato Sintasa/metabolismo , Bacillus subtilis/enzimología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fermentación , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Glucólisis , Análisis de Flujos Metabólicos , Redes y Vías Metabólicas , Metabolómica , Oxígeno/farmacología , Vía de Pentosa Fosfato , Riboflavina/metabolismoRESUMEN
Purpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined. Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ±15%. The matrix effect and recovery were within ±15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration. Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.
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Acetonitrilos , Cromatografía Líquida con Espectrometría de Masas , Piperazinas , Proteínas Proto-Oncogénicas p21(ras) , Pirimidinas , Ratas , Animales , Ratas Sprague-Dawley , Disponibilidad Biológica , Distribución Tisular , Cromatografía Liquida , Espectrometría de Masas en TándemRESUMEN
The minimally invasive surgery through transcranial endoscopic keyhole approach has become the main surgical method for treating cerebral hemorrhage. This method has the advantages of small trauma, short surgical time, low bleeding volume, and fast postoperative recovery. However, this method is not suitable for cases where cerebral hemorrhage occurs again after skull repair surgery. Our team used 3D Slicer reconstruction combined with virtual reality technology to find a suitable keyhole surgical approach and successfully completed a neuroendoscopic removal of basal ganglia hemorrhage through the eyebrow arch keyhole approach in a case of recurrent cerebral hemorrhage after cranioplasty.
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Background and importance: Explore the techniques, advantages and disadvantages of 3D Slicer reconstruction combined with transcranial neuroendoscopy in cerebrospinal fluid rhinorrhea surgery. Clinical presentation: We collected complete clinical data of two patients with cerebrospinal fluid rhinorrhea who underwent minimally invasive surgery using 3D Slicer reconstruction combined with transcranial neuroendoscopy through the supraorbital eyebrow arch keyhole approach in our hospital from June 2022 to May 2023. The patients were one male and one female, aged 50 and 63 years old. At the same time, a retrospective summary of relevant literature at home and abroad in recent years was conducted. 1 case had spontaneous cerebrospinal fluid rhinorrhea with secondary cribriform plate lesion, and the other 1 case had traumatic cerebrospinal fluid rhinorrhea. Both 2 patients were ineffective after long-term conservative treatment, and ultimately recovered after detailed preoperative evaluation and preparation and surgical treatment. Conclusion: Cerebrospinal fluid rhinorrhea is a challenging disease in neurosurgery, and improper management can lead to serious complications such as meningitis. Our team used 3D Slicer reconstruction combined with transcranial endoscopic minimally invasive keyhole surgery to treat cerebrospinal fluid rhinorrhea, achieving good results, proving that this combined technology has certain advantages and is a new surgical technique worth promoting. However, the widespread application and promotion of this technology in anterior skull base surgery still require comprehensive and reliable prospective clinical studies to test.
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To explore the techniques, safety, and feasibility of minimally invasive neurosurgery through the supraorbital eyebrow arch keyhole approach by neuroendoscopy. Retrospective analysis of clinical data of patients with various cranial diseases treated by transcranial neuroendoscopic supraorbital eyebrow keyhole approach in our hospital from March 2021 to October 2023. A total of 39 complete cases were collected, including 21 cases of intracranial aneurysms, 9 cases of intracranial space occupying lesions, 5 cases of brain trauma, 3 cases of cerebrospinal fluid rhinorrhea, and 1 case of cerebral hemorrhage. All patients' surgeries were successful. The good prognosis rate of intracranial aneurysms was 17/21 (81%), and the symptom improvement rate of intracranial space occupying lesions was 8/9 (88.9%). Among them, the initial symptoms of one patient with no improvement were not related to space occupying, while the total effective rate of the other three types of patients was 9/9 (100%). The average length of the craniotomy bone window of the supraorbital eyebrow arch keyhole is 3.77 ± 0.31 cm, and the average width is 2.53 ± 0.23 cm. The average postoperative hospital stay was 14.77 ± 6.59 days. The average clearance rate of hematoma by neuroendoscopy is 95.00% ± 1.51%. Our results indicate that endoscopic surgery through the supraorbital eyebrow arch keyhole approach is safe and effective for the treatment of anterior skull base lesions and cerebral hemorrhage. However, this retrospective study is a single center, small sample study, and the good surgical results do not exclude the subjective screening of suitable patients by clinical surgeons, which may have some bias. Although the clinical characteristics such as indications and contraindications of this surgical method still require further prospective and multicenter clinical research validation, our study still provides a new approach and choice for minimally invasive surgical treatment of anterior skull base lesions.
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Aneurisma Intracraneal , Procedimientos Quirúrgicos Mínimamente Invasivos , Neuroendoscopía , Base del Cráneo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Neuroendoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Anciano , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Base del Cráneo/cirugía , Craneotomía/métodos , Resultado del Tratamiento , Adulto Joven , Procedimientos Neuroquirúrgicos/métodos , Hemorragia Cerebral/cirugíaRESUMEN
The heavy metal contamination in river and lake sediments endangers aquatic ecosystems. Herein, the feasibility of applying different exogenous mesophile consortiums in bioleaching multiple heavy metal-contaminated sediments from Xiangjiang River was investigated, and a comprehensive functional gene array (GeoChip 5.0) was used to analyze the functional gene expression to reveal the intrinsic association between metal solubilization efficiency and consortium structure. Among four consortiums, the Acidithiobacillus thiooxidans and Leptospirillum ferrooxidans consortium had the highest solubilization efficiencies of Cu, Pb, Zn, and Cd after 15 days, reaching 50.33, 29.93, 47.49, and 79.65%, while Cu, Pb, and Hg had the highest solubilization efficiencies after 30 days, reaching 63.67, 45.33, and 52.07%. Geochip analysis revealed that 31,346 genes involved in different biogeochemical processes had been detected, and the systems of 15 days had lower proportions of unique genes than those of 30 days. Samples from the same stage had more genes overlapping with each other than those from different stages. Plentiful metal-resistant and organic remediation genes were also detected, which means the metal detoxification and organic pollutant degradation had happened with the bioleaching process. The Mantel test revealed that Pb, Zn, As, Cd, and Hg solubilized from sediment influenced the structure of expressed microbial functional genes during bioleaching. This work employed GeoChip to demonstrate the intrinsic association between functional gene expression of mesophile consortiums and the bioleaching efficiency of heavy metal-contaminated sediment, and it provides a good reference for future microbial consortium design and remediation of river and lake sediments.
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Sedimentos Geológicos , Metales Pesados , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/química , Contaminantes Químicos del AguaRESUMEN
INTRODUCTION: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. METHODS: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. RESULTS: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was 58.4%. CONCLUSION: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.
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To explore the advantages and disadvantages of 3D Slicer reconstruction and 3D printing localization combined with transcranial neuroendoscope in the surgical treatment of deep cerebral micro cavernous hemangiomas. Method The clinical data of patients with deep cerebral micro cavernous hemangiomas treated by our hospital from June 2022 to February 2023 using 3D Slicer reconstruction and 3D printing localization technology combined with transcranial endoscopic surgery were retrospectively analyzed. A total of 5 cases with complete data were collected, including 2 males and 3 females, aged 9-59 years. All 5 patients had deep supratentorial cavernous hemangiomas with a diameter of less than 1.5 cm, and had clinical symptoms such as headache or epilepsy, and had been diagnosed by CT or MRI. Repeated bleeding from small cavernous hemangiomas in the deep brain can lead to clinical symptoms such as recurrent headache and epilepsy, and is required surgical treatment. However, cavernous hemangiomas often have smaller lesions and are difficult to locate in the deep part. Without neuronavigation, surgery can become extremely difficult. Our team's newly developed 3D Slicer reconstruction and 3D printing localization technology which could provide new options for surgical treatment of small cavernous hemangiomas or other small lesions in the deep brain, but its accuracy and safety still need to be verified by further clinical research.
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Neuroendoscopía , Impresión Tridimensional , Humanos , Femenino , Masculino , Adulto , Adolescente , Niño , Persona de Mediana Edad , Neuroendoscopía/métodos , Estudios Retrospectivos , Adulto Joven , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Hemangioma Cavernoso/cirugía , Hemangioma Cavernoso/diagnóstico por imagen , Hemangioma Cavernoso/patología , Tomografía Computarizada por Rayos XRESUMEN
Lung cancer is one of the most malignant diseases and a major contributor to cancer-related deaths worldwide due to the deficiency of early diagnosis and effective therapy that are of great importance for patient prognosis and quality of life. Over the past decade, the advent of clustered regularly interspaced short palindromic repeats/CRISPR associated protein (CRISPR/Cas) system has significantly propelled the progress of both fundamental research and clinical trials of lung cancer. In this review, we review the current applications of the CRISPR/Cas system in diagnosis, target identification, and treatment resistance of lung cancer. Furthermore, we summarize the development of lung cancer animal models and delivery methods based on CRISPR system, providing novel insights into clinical diagnosis and treatment strategies of lung cancer.
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Lung cancer is an extremely aggressive and highly prevalent disease worldwide, and it is one of the leading causes of cancer death. Deciphering intrinsic genetic mechanism, finding new targets, and overcoming drug resistance are the key to lung cancer treatment. High-throughput CRISPR screening has been extensively used to obtain the genes related to cancers including lung cancer. This review describes CRISPR/Cas9 or CRISPR/dCas9-based technologies for high-throughput screening. We summarize the applications of CRISPR screening technology in exploring the mechanism of lung cancer development in vivo or in vitro, overcoming drug resistance, improving the effect of immunotherapy, and discovering new therapeutic targets. This review highlights the potential of CRISPR screening in combination with tumor barcoding and high-throughput sequencing (Tuba-seq) to precisely quantify the impact of alterations in many tumor suppressor genes on lung cancer.
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BACKGROUND: Ovarian cancer (OV) is a severe and common gynecological disease. Ferroptosis can regulate the progression and invasion of tumors. The immune system is a decisive factor in cancer. The present study aimed to use gene expression data to establish an immunity and ferroptosis-related risk score model as a prognostic biomarker to predict clinical outcomes and the immune microenvironment of OV. METHODS: Common gene expression data were searched from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunity-related genes and ferroptosis-related genes were searched and downloaded from the ImmPort and FerrDb databases, followed by the analysis of the overall survival of patients with OV and the identification of genes. Subsequently, the status of the infiltration of immune cells and the association between immune checkpoints and risk score were assessed. RESULTS: A total of 10 prognostic genes (C5AR1, GZMB, IGF2R, ISG20, PPP3CA, STAT1, TRIM27, TSHR, RB1, and EGFR) were included in the immunity and ferroptosis-related risk score model. The high-risk group had a higher infiltration of immune cells. The risk score, an independent prognostic feature of OV was negatively associated with each immune checkpoint. The risk score may thus help to predict the response to immunotherapy. CONCLUSIONS: The immunity and ferroptosis-related risk score model is an independent prognostic factor for OV. The established risk score may help to predict the response of patients to immunotherapy.
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Ferroptosis , Neoplasias Ováricas , Humanos , Femenino , Ferroptosis/genética , Neoplasias Ováricas/genética , Inmunoterapia , Microambiente Tumoral/genéticaRESUMEN
The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested in or en route to clinical trials, no drugs targeting glucose metabolism pathways have yet been approved to treat breast cancer. Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance. In addition, we summarize the currently available metabolic inhibitors targeting glucose metabolism and discuss the challenges and opportunities in targeting this pathway for breast cancer treatment.
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Background: Cryptorchidism is defined as failure of unilateral or bilateral testicular descent, which increases the risk of infertility and testicular carcinoma. Although there is much research on cryptorchidism, few studies have used the bibliometric analysis method. The purpose of this study was to conduct a comprehensive analysis of cryptorchidism from muti-dimensional perspectives to summarize the research hotspots and trends in cryptorchidism research. Methods: Relevant studies on cryptorchidism were retrieved from the Web of Science Core Collection (WoSCC) database from 2000 to 2022. A comprehensive bibliometric analysis of cryptorchidism was performed by using the CiteSpace, Tableau Public, and VOSviewer software, including the annual distributions of publications, countries, authors, institutions, journals, references, and keywords. Results: From January 1st, 2000 to May 17th, 2022, a total of 5023 papers concerning cryptorchidism were identified for analysis. The USA contributed the most publications (n = 1193) in this field, and the annual number of publications rose rapidly in China. The University of Melbourne published the largest number of papers (n = 131). "Hutson, John M." was the most core author ranked by publications (n = 51), and "Skakkebaek, Niels E." enjoyed the largest number of citations (4441). The JOURNAL OF UROLOGY published the largest number of papers (n = 225), while the average citations per publication of the 75 papers in HUMAN REPRODUCTION reached 62.38. Additionally, burstness analysis of references and keywords showed that cryptorchidism research was mainly focused on the exploration of the optimal mode of treatment for cryptorchidism, including hypogonadism such as Kallmann syndrome and Klinefelter syndrome. Conclusion: Cryptorchidism has attracted continuous attention from the scientific community concerned. International collaboration in the field has witnessed significant growth in recent years and remains essential to further enhance collaborative efforts between scholars from different countries. In addition, the exploration of the optimal treatment modality for cryptorchidism, especially in the prevention of adult infertility, remains a major focus of future research. High-quality follow-up studies are also needed in the future. The pathogenesis (especially at the genetic level) and treatment of hypogonadism such as Kallmann syndrome and Klinefelter syndrome have attracted increasing attention recently, which may usher in some breakthroughs in coming years.
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Subsequently to the publication of this paper, the authors have realized that an error was made during the compilation of Fig. 2A as it appeared on p. 4. Essentially, the partial Q23 images of the '1.56 µm' group were inadvertently copied across to the Q23 images of the '3.12 µm' group, leading to the cell number of the Q23 quadrant being the same for both the 1.56 µm and the 3.12 µm groups, and also leading the total cell number of the 3.12 µm group being calculated as 106.97%, which was clearly incorrect (the total percentage should have added up to 100%). The corrected version of Fig. 2, showing the correct data for the Q23 images in the '3.12 µm' group, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 46: 136, 2021; DOI: 10.3892/or.2021.8087].
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Background: Radiotherapy (RT) is one of the important treatments for various cancer types and its application to prostate cancer (PCa) has also gradually gained increasing attention. However, there is a lack of comprehensive and objective studies on the overall status of research on RT for PCa. This article aims to summarize and quantify the dynamic trends of RT in PCa by using bibliometrics. Methods: Studies on RT for PCa were screened from the Web of Science Core Collection (WoSCC) database between 1 January 2010 and 21 November 2022 to collate and quantify information characteristics by analyzing parameters including annual publications, countries/regions, institutions and authors with the aid of the bibliometric software CiteSpace and VOSviewer. In addition, research trends and hotspots were explored by analyzing keywords and co-cited references. Results: A total of 21338 documents were retrieved. The United States of America (USA) ranked first and maintained the leading position among all countries in the number of publications (8489) and total citations (266342). The University of Toronto was the most active institution in total publications (n=587). Paul L Nguyen enjoyed the most publications (n=179), and Michael J Zelefsky enjoyed the most co-citations (n=3376). INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS published the most papers (n=1026), and was the most frequently co-cited journal (n=78550). The largest and closest cluster in the reference cluster analysis was "oligorecurrent prostate cancer". The timeline view of keywords reveals that cluster "biochemical recurrence(BCR)" is ongoing. Moreover, keywords burstness analysis showed that "radiation dosimetry", "dose rate brachytherapy(BT)", "salvage radiotherapy", "stereotactic body radiotherapy(SBRT)", "guideline", and "multicenter" were the terms with great bursts in the past a few years. Conclusion: The application of RT targeting oligometastatic prostate cancer(OMPC) has garnered considerable attention among researchers. SBRT and BT have become hot topics in the field. Additionally, the BCR of PCa has long been a critical issue requiring extensive research and resolution, and salvage radiotherapy has currently emerged as a closely related research focus. Related large-scale multicenter studies have been conducted over the past few years, providing valuable insights. More high-quality research is expected to be employed to guide clinical decision-making.
RESUMEN
OBJECTIVE: This retrospective study was performed to evaluate the feasibility and safety of surgically clipping intracranial aneurysms using a transcranial neuroendoscopic approach. METHODS: A total of 229 patients with cerebral aneurysms were included in our study, all of whom were treated with clamping surgery at Wuhan University People's Hospital. They were divided into neuroendoscopic and microscopic groups, according to whether or not neuroendoscopy was used for the clamping surgery. We statistically analyzed the patients' baseline data, surgical outcomes, and complications, which were then evaluated to assess the treatment effect. RESULTS: The baseline characteristics were not statistically significant, except for gender, for which the proportions of female patients in the two groups were 69 (56.1%) and 46 (43.4%). There were no patients with incomplete aneurysm clamping or parent vessel occlusion in the neuroendoscopic group, and there were 4 (3.8%) and 2 (1.9%) in the microscopic group, respectively; however, there was no statistically significant difference in the comparison of the two groups. The mean operative times of the two groups were 181 min and 154 min, respectively, and were statistically different. However, the mRS scores of the two groups showed no significant difference in patient prognosis. The differences in complications (including limb hemiplegia, hydrocephalus, vision loss, and intracranial infection) were not statistically significant, except for cerebral ischemia, for which the proportions of patients in the two groups were 8 (6.5%) and 16 (15.1%). CONCLUSIONS: Neuroendoscopy can provide clear visualization and multi-angle views during aneurysm clipping, which is helpful for ensuring adequate clipping and preventing complications.