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2.
Mol Genet Genomics ; 299(1): 66, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980418

RESUMEN

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.


Asunto(s)
Pueblo Asiatico , Fosfatidilinositol 3-Quinasa Clase I , Genotipo , Fenotipo , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Asia Oriental , Pueblo Asiatico/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Pueblos del Este de Asia , Estudios de Asociación Genética , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , Mutación
3.
Orthop Surg ; 16(8): 1903-1911, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38898375

RESUMEN

OBJECTIVES: Tibial tubercle is a crucial player in maintaining the structural integrity and functional stability of the knee joint. Currently, there is no standardized protocol for the classification and treatment of tibial tubercle fractures in adults. This study analyzed the incidence and treatment strategies of tibial tubercle fractures in adults according to the four-column and nine-segment classification system. METHODS: Data of patients with proximal tibial fractures involving tibial tubercle fractures who were treated at our hospital from August 2007 to March 2023 were retrospectively reviewed. The fractures were classified using the AO/OTA classification and four-column and nine-segment classification systems, and the treatment protocol (surgically treated or conservatively treated) was recorded. The number and distribution proportion of patients were counted. A two-sided t-test was conducted to determine the significance of differences between the gender and sides. RESULTS: In total, 169 tibial tubercle fractures were found in 1484 proximal tibial fractures. According to the AO/OTA classification, seven of the 169 patients, (4.1%) were type A, 36 patients (21.3%) were type B, and 126 patients (74.6%) were type C. According to the four-column and nine-segment classification, type 1 cleavage without free fragments was the most common type of fracture (93/169, 55.0%), followed by type 2 dissociative segmental fragments (48/169, 28.4%) and type 3 comminuted fractures (28/169, 16.6%). Overall, 139 of the 169 proximal tibial fractures with tuberosity involvement were treated surgically. Among them, additional fixation of the tubercle fragment was performed in 52 fractures. CONCLUSION: The incidence of tibial tubercle fractures involved in proximal tibial fractures was approximately 11.4% (169/1484) in adults, and approximately one-third of the tubercle bone fragment required additional fixation (30.8%, 52/169). The injury types in the four-column and nine-segment classifications are helpful for accurately judging and making treatment-related decisions for tibial tubercle fractures.


Asunto(s)
Fracturas de la Tibia , Humanos , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/clasificación , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto Joven , Fijación Interna de Fracturas/métodos , Adolescente , Anciano de 80 o más Años , Tratamiento Conservador/métodos
4.
Phys Eng Sci Med ; 47(3): 907-917, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38647634

RESUMEN

We proposed a deep learning approach to classify various error types in daily VMAT treatment of head and neck cancer patients based on EPID dosimetry, which could provide additional information to support clinical decisions for adaptive planning. 146 arcs from 42 head and neck patients were analyzed. Anatomical changes and setup errors were simulated in 17,820 EPID images of 99 arcs obtained from 30 patients using in-house software for model training, validation, and testing. Subsequently, 141 clinical EPID images from 47 arcs belonging to the remaining 12 patients were utilized for clinical testing. The hierarchical convolutional neural network (HCNN) model was trained to classify error types and magnitudes using EPID dose difference maps. Gamma analysis with 3%/2 mm (dose difference/distance to agreement) criteria was also performed. The F1 score, a combination of precision and recall, was utilized to evaluate the performance of the HCNN model and gamma analysis. The adaptive fractioned doses were calculated to verify the HCNN classification results. For error type identification, the overall F1 score of the HCNN model was 0.99 and 0.91 for primary type and subtype identification, respectively. For error magnitude identification, the overall F1 score in the simulation dataset was 0.96 and 0.70 for the HCNN model and gamma analysis, respectively; while the overall F1 score in the clinical dataset was 0.79 and 0.20 for the HCNN model and gamma analysis, respectively. The HCNN model-based EPID dosimetry can identify changes in patient transmission doses and distinguish the treatment error category, which could potentially provide information for head and neck cancer treatment adaption.


Asunto(s)
Estudios de Factibilidad , Neoplasias de Cabeza y Cuello , Redes Neurales de la Computación , Radioterapia de Intensidad Modulada , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Planificación de la Radioterapia Asistida por Computador , Dosificación Radioterapéutica , Equipos y Suministros Eléctricos , Aprendizaje Profundo
5.
Curr Med Imaging ; 20: e15734056293294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644724

RESUMEN

AIM: Our aim was to explore the feasibility of using radiomics data derived from intratumoral and peritumoral edema on fat-suppressed T2-weighted imaging (T2 FS) to distinguish triple-negative breast cancer (TNBC) from non-triple-negative breast cancer (non-TNBC). METHODS: This retrospective study enrolled 174 breast cancer patients. According to the MRI examination time, patients before 2021 were divided into training (n = 119) or internal test (n = 30) cohorts at a ratio of 8:2. Patients from 2022 were included in the external test cohort (n = 25). Four regions of interest for each lesion were defined: intratumoral regions, peritumoral edema regions, regions with a combination of intratumoral and peritumoral edema, and regions with a combination of intratumoral and 5-mm peritumoral. Four radiomic signatures were built using the least absolute shrinkage and selection operator (LASSO) method after selecting features. Furthermore, a radio mic-radiological model was constructed using a combination of intratumoral and peritumoral edema regions along with clinical-radiologic features. Area under the receiver operating characteristic curve (AUC) calculations, decision curve analysis, and calibration curve analysis were performed to assess the performance of each model. RESULTS: The radiomic-radiological model showed the highest AUC values of 0.906 (0.788-1.000) and 82.5 (0.622-0.947) in both the internal and external test sets, respectively. The radiology-radiomic model exhibited excellent predictive performance, as evidenced by the calibration curves and decision curve analysis. CONCLUSION: The ensemble model based on T2 FS-based radiomic features of intratumoral and peritumoral edema, along with radiological factors, performed better in distinguishing TNBC from non-TNBC than a single model. We explored the possibility of developing explainable models to support the clinical decision-making process.


Asunto(s)
Edema , Imagen por Resonancia Magnética , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Femenino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Edema/diagnóstico por imagen , Adulto , Anciano , Curva ROC , Estudios de Factibilidad , Radiómica
6.
Medicine (Baltimore) ; 103(15): e37811, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38608055

RESUMEN

Lipopolysaccharide (LPS) and interleukin-4 (IL-4) play important roles in inducing M1 and M2 macrophage polarization. Studies have shown that LPS can promote the polarization of macrophages to M1-type and produce many pro-inflammatory cytokines, while IL-4 can promote the polarization of macrophages to M2-type and produce many anti-inflammatory cytokines. Moreover, Connexin 43 (Cx43) is widely expressed in macrophages and has various regulatory functions. However, whether Cx43 is involved in the regulation of macrophage M1/M2 polarization has not been fully studied. This study examined the role of Cx43 and M2 polarization markers using Western blot, immunofluorescence, flow cytometry. Cx43 overexpression was induced using Cx43 overexpressing lentivirus. The statistical software SPSS 20.0 (IBM Corp.) and GraphPad Prism 8.0 (GraphPad Software, La Jolla, CA, United States) were used to analyze the results. P values < .05 were considered to indicate statistically significant differences. Our results showed that LPS promotes the polarization of macrophages to M1-type, which is accompanied by an increase in Cx43 expression from 0 to 24 hours. Moreover, the application of the Cx43-specific blockers Gap19 and Gap26 reduces the expression of macrophage M1-type polarization markers. Thus, the expression of Cx43 increases first, and then, due to the initiation of intracellular autophagy during LPS-induced macrophage M1 polarization. Cx43 is degraded and the expression of Cx43 decreases from 24 hours to 48 hours. IL-4 decreases the expression of Cx43 from 24 hours to 48 hours and promotes the transformation of macrophages to M2-type. The application of Cx43 overexpression lentivirus leads to a reduction in the expression of M2 polarization markers. IL-4-induced M2 polarization of macrophages inhibits cell autophagy, reducing Cx43 degradation and leading to an increase in Cx43 from 24 hours to 48 hours. Thus, Cx43 expression in M2-type polarization experiences a reduction at first and then an increase from 24 hours to 48 hours. The direction of macrophage polarization can be controlled by regulating the expression of Cx43, thus providing a theoretical basis for treating atherosclerosis, tumors, and other diseases associated with macrophage polarization.


Asunto(s)
Conexina 43 , Interleucina-4 , Animales , Ratones , Conexina 43/genética , Citocinas , Interleucina-4/inmunología , Lipopolisacáridos/inmunología , Macrófagos
7.
Int J Radiat Biol ; 100(2): 248-255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37747796

RESUMEN

BACKGROUND: The relationship among body mass index (BMI), setup error and radiation pneumonitis is not clearly illustrated. OBJECTIVE: The present study aimed to investigate the role of BMI in non-small cell lung cancer (NSCLC) patients' radiation treatment, focusing on its relationship with setup error of patient positioning, the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and the incidence of radiation pneumonitis. METHODS: This prospective observational study included 523 cases of NSCLC patients during 2020-2022. Patients were divided into different groups by different BMI. The setup error was obtained by cone beam CT (CBCT) at three positions, lateral (LAT), longitudinal (LNG) and vertical (VRT). IMRT dosimetric parameters of V5, V20, and mean dose were collected. RESULTS: Patients with BMI ≥28 kg/m2 showed significantly higher absolute values of LAT, LNG and VRT, higher V5, V20, mean dose, as well as higher total incidence of radiation pneumonitis and grade III radiation pneumonitis compared with patients with BMI <24 kg/m2 or 24-28 kg/m2. Spearman's analysis demonstrated that the absolute values of LAT, LNG and VRT were positively correlated with BMI, and positive correlation existed among BMI, dosimetric parameters and setup errors. ROC curves showed that LAT in setup errors and V5 in dosimetric parameters had the best diagnostic value for prediction of radiation pneumonitis. Only BMI, LAT, V5 and V20 were the independent risk factors for radiation pneumonitis. CONCLUSIONS: Setup error caused by higher BMI might be associated with the dosimetric parameters, as well as the incidence of radiation pneumonitis in NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonitis por Radiación , Radioterapia de Intensidad Modulada , Humanos , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neumonitis por Radiación/epidemiología , Neumonitis por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Índice de Masa Corporal , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/radioterapia , Incidencia , Dosificación Radioterapéutica , Estudios Retrospectivos
8.
Med Phys ; 50(11): 6920-6930, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37800874

RESUMEN

BACKGROUND: Cone-beam computed tomography (CBCT) scanning is used for patient setup in image-guided radiotherapy. However, its inaccurate CT numbers limit its applicability in dose calculation and treatment planning. PURPOSE: This study compares four deep learning methods for generating synthetic CT (sCT) to determine which method is more appropriate and offers potential for further clinical exploration in adaptive proton therapy for nasopharynx cancer. METHODS: CBCTs and deformed planning CT (dCT) from 75 patients (60/5/10 for training, validation and testing) were used to compare cycle-consistent Generative Adversarial Network (cycleGAN), Unet, Unet+cycleGAN and conditionalGenerative Adversarial Network (cGAN) for sCT generation. The sCT images generated by each method were evaluated against dCT images using mean absolute error (MAE), structural similarity (SSIM), peak signal-to-noise ratio (PSNR), spatial non-uniformity (SNU) and radial averaging in the frequency domain. In addition, dosimetric accuracy was assessed through gamma analysis, differences in water equivalent thickness (WET), and dose-volume histogram metrics. RESULTS: The cGAN model has demonstrated optimal performance in the four models across various indicators. In terms of image quality under global condition, the average MAE has been reduced to 16.39HU, SSIM has increased to 95.24%, and PSNR has increased to 28.98. Regarding dosimetric accuracy, the gamma passing rate (2%/2 mm) has reached 99.02%, and the WET difference is only 1.28 mm. The D95 value of CTVs coverage and Dmax value of spinal cord, brainstem show no significant differences between dCT and sCT generated by cGAN model. CONCLUSIONS: The cGAN model has been shown to be a more suitable approach for generating sCT using CBCT, considering its characteristics and concepts. The resulting sCT has the potential for application in adaptive proton therapy.


Asunto(s)
Aprendizaje Profundo , Neoplasias Nasofaríngeas , Terapia de Protones , Tomografía Computarizada de Haz Cónico Espiral , Humanos , Terapia de Protones/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada de Haz Cónico , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapia , Dosificación Radioterapéutica
9.
Sci Rep ; 13(1): 14647, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37669996

RESUMEN

Intracranial chondrosarcoma is a rare tumor with limited reports. We reviewed the clinical outcomes, imaging findings, and pathological characteristics at three centers to improve the diagnosis and treatment of intracranial chondrosarcoma. We retrospectively analyzed 26 patients with intracranial chondrosarcoma who had undergone surgical treatment at Tangdu Hospital of Air Force Military Medical University, Mianyang Central Hospital, and Nanchong Central Hospital from January 2010 to July 2022. Clinical manifestations, imaging features, surgical treatment, prognosis, and overall survival (OS) were analyzed. All 26 chondrosarcomas were located at the skull base. Gross total resection (GTR), subtotal resection (STR), and partial resection (PR) were performed in 14, 10, and 2 cases, respectively. Four cases underwent endoscopic transnasal surgery, while the remaining cases underwent craniotomy. The clinical symptoms were evaluated 1 week after surgery, and 15 cases were relieved to varying degrees. Postoperative complications included pulmonary infection, subcutaneous hydrops, dysphagia and choking, facial numbness, abducens paralysis, and intracranial infection (ICI). Fifteen cases received postoperative adjuvant radiotherapy. Seven cases showed recurrence: two with PR, four with STR, and one with GTR. Six cases received reoperation or radiotherapy after tumor progression, and one untreated patient died 5 months after tumor recurrence. The extent of tumor resection (HR 21.74, 95% CI 1.25-376.6, P = 0.03) and pathological grading (HR 131.99, 95% CI 4.05-4300.5, P = 0.006) were associated with improved OS. We presented our experience in the treatment of intracranial chondrosarcoma at three centers in the past 12 years. Intracranial chondrosarcoma lacked typical imaging features and are difficult to differentiate from other skull base lesions. Maximum extent of tumor resection with minimal injury to neurological function remains the most important treatment strategy. The extent of surgical resection and pathological grading were found to be predictors for OS.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Humanos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia , Reoperación , Estudios Retrospectivos
11.
Front Oncol ; 13: 1182261, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37434973

RESUMEN

Background: Choroid plexus papilloma (CPP) is rare and even rarer in infants and young children, and it usually occurs in the ventricles. Due to the physical peculiarities of infants, tumor removal by microscopic or endoscopic surgery alone is difficult. Case Presentation: A 3-month-old patient was found to have an abnormally enlarged head circumference for 7 days. Cranial magnetic resonance imaging (MRI) examination revealed a lesion in the third ventricle. The patient underwent combined microscopic and endoscopic "chopstick" technique to remove the tumor. He recovered well after the surgery. Postoperative pathological examination revealed CPP. Postoperative MRI suggested total resection of the tumor. Follow-up for 1 month showed no recurrence or distant metastasis. Conclusions: Combined microscopic and endoscopic "chopstick" technique may be a suitable approach to remove tumors in infant ventricles.

12.
J Mol Med (Berl) ; 101(8): 931-945, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37380866

RESUMEN

Organoids have been developed in the last decade as a new research tool to simulate organ cell biology and disease. Compared to traditional 2D cell lines and animal models, experimental data based on esophageal organoids are more reliable. In recent years, esophageal organoids derived from multiple cell sources have been established, and relatively mature culture protocols have been developed. Esophageal inflammation and cancer are two directions of esophageal organoid modeling, and organoid models of esophageal adenocarcinoma, esophageal squamous cell carcinoma, and eosinophilic esophagitis have been established. The properties of esophageal organoids, which mimic the real esophagus, contribute to research in drug screening and regenerative medicine. The combination of organoids with other technologies, such as organ chips and xenografts, can complement the deficiencies of organoids and create entirely new research models that are more advantageous for cancer research. In this review, we will summarize the development of tumor and non-tumor esophageal organoids, the current application of esophageal organoids in disease modeling, regenerative medicine, and drug screening. We will also discuss the future prospects of esophageal organoids.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Humanos , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Organoides , Medicina Regenerativa
13.
Acta Diabetol ; 60(9): 1155-1169, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37199797

RESUMEN

AIMS: To conduct a systematic review to summarize the definition, measurement tools, prevalence, and contributing factors of impaired awareness of hypoglycemia (IAH) in type 2 diabetes mellitus (T2DM). METHODS: A reproducible search strategy was used to identify factors affecting IAH in T2DM in PubMed, MEDLINE, EMBASE, Cochrane, PsycINFO, and CINAHL from inception until 2022. Literature screening, quality evaluation, and information extraction were performed independently by 2 investigators. A meta-analysis of prevalence was performed using Stata 17.0. RESULTS: The pooled prevalence of IAH in patients with T2DM was 22% (95%CI:14-29%). Measurement tools included the Gold score, Clarke's questionnaire, and the Pedersen-Bjergaard scale. IAH in T2DM was associated with sociodemographic factors (age, BMI, ethnicity, marital status, education level, and type of pharmacy patients visited), clinical disease factors (disease duration, HbAlc, complications, insulin therapy regimen, sulfonylureas use, and the frequency and severity of hypoglycemia), and behavior and lifestyle (smoking and medication adherence). CONCLUSION: The study found a high prevalence of IAH in T2DM, with an increased risk of severe hypoglycemia, suggesting that medical workers should take targeted measures to address sociodemographic factors, clinical disease, and behavior and lifestyle to reduce IAH in T2DM and thus reduce hypoglycemia in patients.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglucemia , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Prevalencia , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Hipoglucemia/diagnóstico , Insulina/uso terapéutico , Hipoglucemiantes/efectos adversos
14.
BMC Musculoskelet Disord ; 24(1): 245, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997942

RESUMEN

PURPOSE: The purpose of this study was to describe and evaluate the use of a specially designed hollow trephine to create the entry point through the femoral condyle during retrograde interlocking intramedullary nailing for femoral fractures. METHODS: From June 2019 to December 2021, we treated 11 patients (5 men, 6 women; mean age, 64 years; age range 40-77 years) with mid-distal femoral fractures by retrograde intramedullary femoral nailing using a self-designed hollow trephine for femoral condyle reaming and cancellous bone harvesting. The mode of all the nails is static. Patients were followed up at 1, 4, 8, and 12 weeks and for at least 6 months after surgery. The healing process and heterotopic ossification were evaluated by imaging. Partial weight bearing was permitted during the recovery period and complete weight bearing was permitted after clinical healing of the fracture displayed by X-ray. RESULTS: The operation was successful in all patients. Over mean follow-up of 9.3 months (range, 6.0-12.0 months), all patients achieved clinical healing within three months. There were no complications such as knee joint infection, heterotopic ossification, knee joint adhesion and wedge effect. CONCLUSION: The use of the hollow trephine during femoral retrograde intramedullary nailing helps avoid postoperative complications such as heterotopic ossification, knee joint adhesions, and wedge effect. It also facilitates bone graft harvesting.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Osificación Heterotópica , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Clavos Ortopédicos , Curación de Fractura , Fémur/diagnóstico por imagen , Fémur/cirugía , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Resultado del Tratamiento
15.
Ann Plast Surg ; 90(5S Suppl 2): S209-S215, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36729078

RESUMEN

ABSTRACT: Hyperactivation of the PI3K/AKT/mTOR signaling pathway caused by PIK3CA mutations is associated with a category of overgrowth syndromes that are defined as PIK3CA -related overgrowth spectrum (PROS). The clinical features of PROS are highly heterogeneous and usually present as vascular malformations, bone and soft tissue overgrowth, and neurological and visceral abnormalities. Detection of PIK3CA variants is necessary for diagnosis and provides the basis for targeted therapy for PROS. Drugs that inhibit the PI3K pathway offer alternatives to conventional therapies. This article reviews the current knowledge of PROS and summarizes the latest progress in precise treatment, providing new insights into future therapies and research goals.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Malformaciones Vasculares , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Mutación , Transducción de Señal , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Síndrome , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/genética , Malformaciones Vasculares/terapia
16.
Biochem Genet ; 61(3): 979-994, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36334237

RESUMEN

Glioma is the most common tumor of the central nervous system, and its poor prognosis can be linked to hypoxia and gene inactivation. Na+/Ca2+ exchanger 2 (NCX2) is expressed only in the normal brain and not in other tissues or glioma. We constructed a hypoxic microenvironment to more accurately understand the effect of NCX2 in glioma. Our previous experiments confirmed that NCX2 inhibited the growth of U87 cells in nude mice, indicating that NCX2 is a potential tumor suppressor gene. Malignant tumor cells are often exposed to an anoxic environment. To more accurately understand the effect of NCX2 in glioma, we constructed a hypoxic microenvironment. To detect the localization of NCX2 in transfected U87 cells, immunofluorescence was used. We tested the function of NCX2 in glioma, i.e., how it contributes to the cytosolic Ca2+ homeostasis by X-Rhod-1. We tested the cell proliferation of NCX2 in glioma in hypoxic using Cell counting kit-8 (CCK8). Cell migration and invasion were evaluated in 24-well transwell matrigel-coated or non-matrigel-coated in hypoxia. NCX2 promoted the proliferation of U87 cells in the hypoxic microenvironment. It inhibited the invasion and migration abilities of U87 cells. We demonstrated that NCX2 was located on the cell membrane and that it reduced intracellular Ca2+ levels and reactivated P53 and PTEN. We further demonstrated that NCX2 impaired cell invasion through the HIF-1α pathway in glioma. The results indicated that NCX2 plays a key role in glioma formation and tumor invasion functionality.


Asunto(s)
Calcio , Glioma , Animales , Ratones , Calcio/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Hipoxia/genética , Hipoxia/metabolismo , Ratones Desnudos , Invasividad Neoplásica/genética , Microambiente Tumoral , Humanos
17.
J Vasc Surg Venous Lymphat Disord ; 11(2): 397-403.e1, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36328137

RESUMEN

OBJECTIVE: Consumptive coagulopathy treatment and pain management are crucial for patients with venous malformations (VMs). Dabigatran etexilate, a non-vitamin K antagonist oral anticoagulant, has known advantages compared with low-molecular-weight heparin and vitamin K antagonists, including oral administration, a more consistent pharmacokinetics/pharmacodynamics profile, a better safety profile, and no need for coagulation surveillance. In the present study, we tested the efficacy and safety of dabigatran etexilate for consumptive coagulopathy treatment and pain management for patients with VMs. METHODS: To investigate the efficacy and safety of dabigatran etexilate in treating localized intravascular coagulation (LIC) associated with VM, we retrospectively collected data for 19 outpatients with VM and LIC, who had been treated with dabigatran etexilate from September 2019 to June 2021. The patients provided oral informed consent and underwent biologic blood testing, routine examinations, and determination of coagulation function before and after treatment. The dosage of dabigatran etexilate was 110 mg twice daily for adults and 55 mg twice daily for children. RESULTS: All 19 patients had benefited from dabigatran etexilate treatment with coagulation improvement and pain relief. Pain had improved in all 16 evaluable patients. The fibrinogen and D-dimer levels had improved in 18 of 19 patients. The fibrin degradation product level had improved in 10 of 14 patients. None of patients reported lesion regression, appearance changes, or improvement in mobility. No significant differences were found in the D-dimer, fibrinogen, and fibrin degradation product levels between the short-term (<10 days) and long-term (≥10 days) use of the medication. Dabigatran etexilate was well tolerated by all patients. No bleeding event had occurred during follow-up. CONCLUSIONS: The results of our study have confirmed the efficacy and safety of dabigatran etexilate in treating pain and LIC in patients with VMs. Dabigatran etexilate is a suitable choice preoperatively to modify coagulation function and pain in patients with VMs.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Malformaciones Vasculares , Adulto , Niño , Humanos , Dabigatrán/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Estudios Retrospectivos , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Malformaciones Vasculares/complicaciones , Fibrinógeno/uso terapéutico , Fibrinolíticos/uso terapéutico , Dolor
18.
Se Pu ; 40(10): 937-943, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36222257

RESUMEN

Emerging pollutants (EPs) are chemical substances that are commonly not regulated and can be detected at low or very low concentrations. However, EPs have triggered special concern because their long-term adverse effects on the environment and human health remain unknown. Most EPs show biological toxicity, environmental persistence, and bioaccumulation. Even at low concentrations in the environment, EPs may pose significant environmental and health risks. Therefore, their treatment has been explicitly included in the 14th Five Year Plan for National Economic and Social Development of the People's Republic of China and the Outline of the Long-term Goals for 2035. Soil is a source of pollutants, and its quality is directly related to economic development, ecological security, and people's livelihood. At present, China's soil environmental monitoring system is not perfect, and the ability to monitor these new organic pollutants is lagging. Therefore, to strengthen the supervision of construction and agricultural land soil environments, it is essential to strengthen the soil environment monitoring ability for these EPs and establish a reliable, steady, and economic analysis method, including their separation and analysis methods in soil. Polychlorinated naphthalenes (PCNs) have received considerable attention as emerging halogenated compounds. They were listed in Annexes A and C of the Stockholm Convention on persistent organic pollutants (POPs) in 2015 because of their persistence, multimedia fate, and toxicity. PCNs have now been detected in the surrounding soils. Owing to their trace levels in complex soil, high requirements have been put forward for the pretreatment and instrument analysis of PCNs. This study aims to develop a new method for the selective purification of PCNs in soil, which can not only effectively remove lipids and other interferences in soil but also effectively reduce time, labor, and material costs in the pre-treatment process. Based on the physicochemical properties of the 13X molecular sieve, it was explored to purify soil-extracts as solid-phase extraction (SPE) sorbents. With n-hexane as the loading and rinsing solvent, 10 mL of a dichloromethane/n-hexane mixture (2∶15, v/v) was used to elute the PCNs. Moreover, selective separation of target substances from lipid macromolecules and other interferences could be achieved simultaneously. For the selective separation of PCNs, the average recovery of the internal standard could reach 56.1% to 88.0%. 13X molecular sieves are superior to gel permeation chromatography (GPC) and Florisil SPE, and they exhibit good cleanup efficiency similar to a multilayer silica gel/alumina column (53.0%-117.0%). Although the obtained recoveries are not as high as those obtained with a multilayer silica gel/alumina column, 13X molecular sieves have advantages in terms of simple operation, environmental friendliness, and low cost. Based on these fundamental experiments, accelerated solvent extraction was used to extract targets in soil, molecular sieves were used as SPE sorbents for purification, and GC-MS/MS was employed for PCN analysis. This method was developed as a systematic analytical method for PCNs determination. The method detection limits (MDLs) for PCN homologs were in the range of 0.009-0.6 ng/g. The precision and accuracy of the method were evaluated using spiked matrices. At three spiked levels (4, 10, and 18 ng), the recoveries of PCNs (CN-3, 13, 42, 46, 52, 53, 73, and 75) were 70%-128%, 71%-115%, and 61%-114%, respectively, and the corresponding relative standard derivations were 4.2%-23%, 6.5%-31% and 4.7%-22%. Thus, this method meets the requirements of trace analysis and shows acceptable parallelism, sensitivity, accuracy, and precision, thus being feasible for the analysis of emerging pollutant. The method is expected to play an important role in sample pretreatment in the future, especially for the nationwide investigation of soil pollution.


Asunto(s)
Contaminantes Ambientales , Suelo , Humanos , Óxido de Aluminio , Contaminantes Ambientales/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Hexanos , Lípidos , Cloruro de Metileno/análisis , Naftalenos/análisis , Contaminantes Orgánicos Persistentes , Gel de Sílice , Extracción en Fase Sólida , Solventes/análisis , Espectrometría de Masas en Tándem
19.
Se Pu ; 40(7): 644-652, 2022 Jul.
Artículo en Chino | MEDLINE | ID: mdl-35791603

RESUMEN

Polychlorinated naphthalenes (PCNs) have a structure similar to that of polychlorinated biphenyls (PCBs) and represent a new type of persistent organic pollutants (POPs) that are widely present in the environment and biological communities. PCNs can migrate and transform via different environmental media, which severely affects the health of humans and organisms. Researchers have devoted considerable focus on ambient air pollution. Although the current ambient air quality has not yet limited the concentration of PCNs, the Stockholm Convention has required parties to prohibit and eliminate their production and use. As one of the contracting parties, China is obligated to improve its environmental monitoring. In other words, the development of a method for monitoring PCNs in ambient air is important for understanding ambient air quality and safeguarding human health. PCNs are generally present at trace levels (pg/m3) in ambient air. To achieve accurate quantification of PCNs, high demands are raised on the methods for extraction, purification, and instrumental analysis, which can directly affect the efficiency, accuracy, and sensitivity of a method. Considering the trace-level presence of PCNs in ambient air and the high efficiency and accuracy of the analytical method, accelerated solvent extraction (ASE), combined with column chromatography using a multilayer silica gel column and a neutral alumina column, was established for the extraction and purification of PCNs in ambient air. The important parameters involved in the aforementioned steps, such as the type of extraction and volume of elution solvent, were optimized. The results indicated that dichloromethane-hexane (1∶1, v/v) was the best extraction solvent for the recovery of PCNs. Hexane and dichloromethane-hexane (5∶95, v/v) were used as the elution solvents for the multi-silica gel column and neutral alumina column, respectively. Isotope dilution gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) was used to quantify the target compounds. Gas chromatographic parameters, such as temperature program conditions and inlet temperature, were also optimized. The oven temperature program was as follows: 80 ℃ for 1 min, 80 ℃ to 160 ℃ at 15 ℃/min, 160 ℃ to 265 ℃ at 3 ℃/min, and 265 ℃ to 280 ℃ at 5 ℃/min, followed by holding the temperature at 280 ℃ for 10 min. The inlet temperature was set at 260 ℃. The optimal characteristics of ion pair, collision energy, and ion source temperature were determined by optimizing the key mass spectrometry parameters. The developed instrumental method, combined with suitable sample preparation techniques, was used to determine the concentrations of PCNs in ambient air samples. Quality control (QC) and quality assurance (QA) were performed by adding isotope internal standards before sampling, extraction, and injection analysis to monitor the entire analysis process. The relative standard deviations (RSDs) of the relative response factors (RRFs) for trichloronaphthalene to octachloronaphthalene were less than 16% in the concentration range of 2-100 ng/mL. The method detection limits (MDLs) for PCN homologues were in the range of 1-3 pg/m3(calculated using a sample volume of 288 m3). The precision and accuracy of this method for determining PCNs in ambient air samples were evaluated using a spiked matrix. The average spiked recoveries of trichloronaphthalene to octachloronaphthalene were 89.0%-119.4%, 98.6%-122.5% and 93.7%-124.5% at low, medium, and high spiked concentrations (20, 50, and 90 ng/mL), respectively. The RSDs of the assay results were 1.9%-7.0%, 1.6%-6.6%, and 1.0%-4.8%, respectively. During the entire analysis process, the average recoveries of the sampling and extracted internal standards were 136.2%-146.0% and 42.4%-78.1%, respectively, and the corresponding RSDs were 5.6%-7.5% and 2.7%-17.5%. Thus, this method meets the requirements of trace analysis and exhibits good parallelism, high sensitivity, high accuracy, and good precision, and it is suitable for the accurate quantitative determination of trichloronaphthalene to octachloronaphthalene in ambient air.


Asunto(s)
Hexanos , Naftalenos , Óxido de Aluminio , Cromatografía de Gases y Espectrometría de Masas/métodos , Hexanos/análisis , Humanos , Isótopos , Cloruro de Metileno/análisis , Naftalenos/análisis , Gel de Sílice , Solventes/análisis , Espectrometría de Masas en Tándem/métodos
20.
Front Oncol ; 12: 865865, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35692788

RESUMEN

Objective: To improve the diagnosis and treatment of intracranial chondromas (ICDs) by discussing the clinical manifestations and imaging characteristics of ICDs, as well as surgical methods and treatment strategies. Methods: We retrospectively analyzed 17 patients diagnosed with ICDs who underwent microsurgery or endoscopic transsphenoidal surgery at the Tangdu Hospital of Air Force Military Medical University and the Mianyang Central Hospital from January 2010 to November 2021. Clinical manifestations, imaging examinations, surgical treatments, and prognosis of these patients were analyzed. Results: ICDs had often been misdiagnosed as craniopharyngioma, chordoma, schwannoma, cavernous hemangioma, pituitary adenoma, and meningioma before surgery. Of the 17 cases, gross total resection (GTR) was performed in 10 cases, subtotal resection (STR) in 5, and partial resection in 2. GTR of tumor was achieved in eight cases via the endoscopic endonasal transsphenoidal approach (EETA) or the extended endoscopic endonasal transsphenoidal approach (EEETA), and the remaining patients underwent craniotomies. Clinical symptoms were assessed 1 week after surgery, 10 cases were relieved at varying degrees, and four cases had no improvement. Postoperative complications included right-limb hemiparesis, diplopia, eyelid ptosis, pulmonary infection, subcutaneous hydrops, cerebrospinal-fluid leakage (CSFL), and intracranial infection (ICI). One patient received gamma knife treatment at 3 months after surgery, two patients died due to tumor progression, and the remaining patients had no tumor recurrence. Conclusions: ICDs lack typical imaging features and are often misdiagnosed. The EETA or EEETA helps improve the surgical outcomes and GTR rates of ICDs at different sites.

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