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Testicular tumors represent a common form of solid tumor in young men, with choriocarcinoma of the testis being a rare, non-granulomatous germ cell tumor. It accounts for less than 0.3% of all testicular germ cell tumors. Pelvic and pulmonary metastases originating from testicular choriocarcinoma are exceptionally uncommon in men. This study describes a case of a 27-year-old male diagnosed with testicular choriocarcinoma, presenting initially with nausea, vomiting, and abdominal pain. Furthermore, this review encompasses cases of testiclar choriocarcinoma in individuals aged 30 years and below, both in China and internationally, over the past 20 years.
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There are few reports of poisoning caused by high-dose intravenous injection of mercury. Its clinical manifestations are diverse and the risk of mortality is high. Currently, the pathogenesis is not clear and the treatment experience is insufficient, leading to difficulties in clinical diagnosis and treatment. In this article, the data of a case of mercury poisoning caused by intravenous self-administration was analyzed and summarized. The patient developed multiple organ dysfunction syndrome after intravenous injection of high-dose mercury. After comprehensive treatment, such as mercury removal, organ support, and infection prevention, the condition was improved. This case suggests that intravenous injection of mercury can cause damage to the functions of multiple organs, such as the heart, lungs, and kidneys. Early treatment and intervention can bring benefits.
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Intoxicação por Mercúrio , Mercúrio , Humanos , Intoxicação por Mercúrio/tratamento farmacológico , Injeções Intravenosas , Masculino , Insuficiência de Múltiplos Órgãos/induzido quimicamente , AdultoRESUMO
The quantity and quality of dissolved organic matter (DOM) exported from source areas are closely related to hydrological linkage between source areas and streams, that is hydrological connectivity. However, understanding of how hydrological connectivity regulates the export of catchment DOM components remains inadequate. In this study, high-frequency monitoring of groundwater and runoff from subtropical humid catchment was conducted for 20 months, and hydrological connectivity was quantitatively characterized by considering both surface and subsurface hydrological processes. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was utilized to investigate the DOM molecular composition. Results showed that over half of the areas in the catchment could not persistently establish hydrological connectivity with the stream during the rainfall. The average proportion of lignin was the highest in DOM components, followed by tannin and proteins. Additionally, both modified aromaticity index and double bond equivalence reached maximums at peak discharge, reflecting terrestrial materials could increase DOM aromaticity and unsaturated degree. Partial least square-structural equation modeling revealed significantly direct effects of rainfall, antecedent conditions, and hydrological connectivity on dissolved organic carbon (DOC) export. Furthermore, nonlinear relationships were observed between hydrological connectivity and DOC, tannin, and condensed aromatics. Specifically, the instantaneous DOC flux increased dramatically when the hydrological connectivity strength exceeded 0.14; tannin and condensed aromatics exhibited a rapid increase with rising connectivity strength, but remained stable at connectivity strength above 0.25. However, hydrological connectivity showed no significant correlation with unstable components (such as lipids, protein, amino sugars, and carbohydrates). These results provide new insights into hydrological controls on the quantity and quality of DOM export and contribute to developing appropriate catchment management strategies for carbon storage.
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Água Subterrânea , Hidrologia , Água Subterrânea/química , Rios/química , Monitoramento Ambiental , Taninos/análise , Compostos Orgânicos/análise , ChuvaRESUMO
PURPOSE: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time. DESIGN: Systematic review and meta-analysis. METHODS: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies. FINDINGS: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%). CONCLUSIONS: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks.
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PURPOSE: Thyroid cancer has an overwhelming incidence in the population. Thus, there is an urgent need to understand the underlying mechanism of its occurrence and development, which may provide new insights into therapeutic strategies. The role and mechanism of TFCP2L1 in regulating the progression of thyroid cancer remains unclear. METHODS: Public databases and clinical samples were used to detect the expression of TFCP2L1 in cancer and non-cancer tissues. Kaplan-Meier and Cox regression analyses were used to compare the differences in survival probability of the TFCP2L1 highly expressing group and the TFCP2L1 lowly expressing group. Functional assays were used to evaluate the biological effect of TFCP2L1 on thyroid cancer cells. RNA sequencing and enrichment analyses were used to find out pathways that were activated or inactivated by TFCP2L1. RESULTS: We demonstrated that TFCP2L1 was significantly downregulated in thyroid cancer. Decreased expression of TFCP2L1 was associated with malignant clinicopathological characteristics. Kaplan-Meier and Cox regression analyses indicated that thyroid tumor patients with low TFCP2L1 expression presented shorter disease-free interval and progression-free interval. Additionally, TFCP2L1 expression was positively correlated with thyroid differentiation degree. Overexpression of TFCP2L1 in thyroid cancer cells inhibited cell growth and motility in vitro, and tumorigenicity and metastasis in vivo. Mechanistically, the NF-κB signaling pathway was found inactivated by overexpressing TFCP2L1. CONCLUSION: Our results suggest that TFCP2L1 is a tumor suppressor and potential differentiation regulator, and might be a potential therapeutic target in thyroid cancer.
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OBJECTIVE: To investigate the protective effects of HTD4010 against lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) in mice and explore the mechanisms mediating its effect. METHODS: Forty-five male ICR mice were randomized equally into control group, LPS (10 mg/kg) group, and LPS+HTD4010 group (in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection). Cardiac function of the mice was evaluated by ultrasound, and pathological changes in the myocardial tissues were observed with HE staining. The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA, and apoptosis of the cardiomyocytes was detected with TUNEL staining. The expression levels of the key proteins associated with apoptosis, autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting. The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy. RESULTS: LPS exposure caused severe myocardial damage in mice, characterized by myocardial fiber rupture, structural disorder, inflammatory cell infiltration, and mitochondrial damage. The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values, elevated IL-6 and TNF-αlevels in serum and myocardial tissue, and an increased myocardial cell apoptosis rate with enhanced expressions of Bax, p-62 and p-mTOR and lowered expressions of Bcl-2, LC3 II/I, Beclin-1 and p-AMPK (P < 0.05 or 0.01). Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage, increased LVEF and FS values, reduced IL-6 and TNF-α levels in serum and myocardial tissue, decreased cardiomyocyte apoptosis, lowered myocardial expressions of Bax, p-62 and p-mTOR, and increased Bcl-2, LC3 II/I, Beclin-1 and p-AMPK expressions (P < 0.05 or 0.01). CONCLUSION: HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.
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Cardiomiopatias , Traumatismos Cardíacos , Camundongos , Masculino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Beclina-1/metabolismo , Lipopolissacarídeos/efeitos adversos , Interleucina-6/metabolismo , Proteína X Associada a bcl-2/metabolismo , Camundongos Endogâmicos ICR , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Miócitos Cardíacos , Traumatismos Cardíacos/metabolismo , Apoptose , AutofagiaRESUMO
OBJECTIVE: To develop a method for accurate identification of multiscale carotid plaques in ultrasound images. METHODS: We proposed a two-stage carotid plaque detection method based on deep convolutional neural network (SM-YOLO).A series of algorithms such as median filtering, histogram equalization, and Gamma transformation were used to preprocess the dataset to improve image quality. In the first stage of the model construction, a candidate plaque set was built based on the YOLOX_l target detection network, using multiscale image training and multiscale image prediction strategies to accommodate carotid artery plaques of different shapes and sizes. In the second stage, the Histogram of Oriented Gradient (HOG) features and Local Binary Pattern (LBP) features were extracted and fused, and a Support Vector Machine (SVM) classifier was used to screen the candidate plaque set to obtain the final detection results. This model was compared quantitatively and visually with several target detection models (YOLOX_l, SSD, EfficientDet, YOLOV5_l, Faster R-CNN). RESULTS: SM-YOLO achieved a recall of 89.44%, an accuracy of 90.96%, a F1-Score of 90.19%, and an AP of 92.70% on the test set, outperforming other models in all performance indicators and visual effects. The constructed model had a much shorter detection time than the Faster R-CNN model (only one third of that of the latter), thus meeting the requirements of real-time detection. CONCLUSION: The proposed carotid artery plaque detection method has good performance for accurate identification of carotid plaques in ultrasound images.
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Estenose das Carótidas , Placa Aterosclerótica , Humanos , Artérias Carótidas/diagnóstico por imagem , Redes Neurais de Computação , Algoritmos , Placa Aterosclerótica/diagnóstico por imagemRESUMO
Objective: To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province. Methods: Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden. Results: From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women. Conclusions: The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.
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Hepatite A , Hepatite B , Adulto , Masculino , Criança , Humanos , Feminino , Idoso , Hepatite A/epidemiologia , Efeitos Psicossociais da Doença , Hepatite B/epidemiologia , Incidência , China/epidemiologia , Carga Global da Doença , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: Both non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are prevalent diseases worldwide. This study aimed to explore the underlying mechanisms of NAFLD and HCC and identify new therapeutic targets for human cancers. MATERIALS AND METHODS: NAFLD and HCC gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify co-expressed genes associated with NAFLD and HCC. Public databases were consulted to find common targets of NAFLD and HCC. Enrichment analysis and CIBERSORT techniques were employed to analyze the pathways enriched with DEGs and the attributes of infiltrating immune cells. Furthermore, the expression data of UROC1 and clinical information of patients were acquired from The Cancer Genome Atlas (TCGA) database. Finally, the expression of the UROC1 was validated by immunohistochemistry (IHC). RESULTS: Through a comprehensive bioinformatics analysis, eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1) were identified. Enrichment analysis indicated that inflammatory and immune response may be common features between NAFLD and HCC. CIBER-SORT analysis revealed an imbalance of plasma cells and macrophages in NAFLD and HCC. Pan-cancer analysis demonstrated that UROC1 expression was related to clinical outcomes and tumor immunity in various cancers. Moreover, a strong correlation was exhibited between UROC1 expression and crucial elements, including tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints (ICP), and tumor microenvironment (TME). Importantly, an adverse clinical prognosis of HCC was linked to decreased UROC1 expression, which was consistent with IHC results. CONCLUSIONS: We identified eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1), which may become early diagnostic and therapeutic targets for NAFLD and HCC. The pan-cancer analysis of UROC1 provides new evidence for its broad application prospects in the field of HCC and other cancers.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/genética , Hepatopatia Gordurosa não Alcoólica/genética , Prognóstico , Interleucina-6 , Neoplasias Hepáticas/genética , Microambiente Tumoral/genética , ATPases Associadas a Diversas Atividades Celulares , Proteínas Associadas aos Microtúbulos , Proteínas NuclearesRESUMO
AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival. CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Retais , Adulto , Humanos , Resultado do Tratamento , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Intervalo Livre de Doença , Quimiorradioterapia/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Resposta Patológica Completa , FluoruracilaRESUMO
Subsurface runoff represents the main pathway of nitrate transport in hilly catchments. The magnitude of nitrate export from a source area is closely related to subsurface hydrological connectivity, which refers to the linkage of separate regions of a catchment via subsurface runoff. However, understanding of how subsurface hydrological connectivity regulates catchment nitrate export remains insufficient. This study conducted high-frequency monitoring of shallow groundwater in a hilly catchment over 17 months. Subsurface hydrological connectivity of the catchment over 38 rainfall events was analyzed by combining topography-based upscaling of shallow groundwater and graph theory. Moreover, cross-correlation analysis was used to evaluate the time-series similarity between subsurface hydrological connectivity and nitrate flux during rainfall events. The results showed that the maximum subsurface hydrological connectivity during 32 out of 38 rainfall events was below 0.5. Although subsurface flow paths (i.e., the pathways of lateral subsurface runoff) exhibited clear dynamic extension and contraction during rainfall events, most areas in the catchment did not establish subsurface hydrological connectivity with the stream. The primary pattern of nitrate export was flushing (44.7%), followed by dilution (34.2%), and chemostatic behavior (21.1%). A threshold relationship between subsurface hydrological connectivity and nitrate flux was identified, with nitrate flux rapidly increasing after the subsurface connectivity strength exceeded 0.121. Moreover, the median value of cross-correlation coefficients reached 0.67, which indicated subsurface hydrological connectivity exerts a strong control on nitrate flux. However, this control effect is not constant and it increases with rainfall amount and intensity as a power function. The results of this study provide comprehensive insights into the subsurface hydrological control of catchment nitrate export.
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Água Subterrânea , Nitratos , Nitratos/análise , Movimentos da Água , Rios , HidrologiaRESUMO
We aimed to analyze the clinical data of 10 patients (6 male and 4 female) with Fabry disease (FD). The mean age of the patients was (28.80±9.27) years. Seven patients had classical FD and three had delayed onset FD. Among the 10 patients, six had skin involvement and cutaneous angiokeratoma; five had hypohidrosis or anhidrosis; nine had intermittent neuralgia; and three had supraorbital ridge protrusion, forehead bulge, and lip thickening. Five patients had proteinuria, including one with chronic kidney disease stage 3 and one with chronic kidney disease stage 5. Cardiac involvement occurred in three patients, two had myocardial hypertrophy and one had valvular insufficiency. The activity of galactosidase decreased in seven patients (2.80-1.55 µmol·L-1·h-1). Plasma deacetyl-GL-3 was elevated in all 10 patients(3.12-120.00 ng/ml). Three patients underwent renal biopsy, wherein two cases of focal segmental glomerulosclerosis and one of mesangial proliferative glomerulonephritis was found. A large number of myeloid and zebra bodies were found in the podocytes in three patients, including a small number of myeloid and zebra bodies in the renal tubular epithelial cells in one patient with occasional zebra bodies in the renal interstitium. Nine patients had GLA gene mutations. One patient was c.102T>A, a de novo mutation. Four patients were treated with agalsidase α injection (0.2 mg/kg, intravenous infusion every 2 weeks), and their prognosis was good. FD has various clinical manifestations and multi-system involvement, which requires multidisciplinary cooperation. Detection of galactosidase activity, plasma globotriaosylsphingosine, and GLA gene mutation can help for accurate diagnosis.
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Doença de Fabry , Hipo-Hidrose , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Animais , Adulto Jovem , Adulto , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Galactosidases , EquidaeRESUMO
BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.
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Antineoplásicos , Neoplasias da Mama , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Recombinação Homóloga , Mutação , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
Hematopoietic stem cell transplantation (HSCT) is the only approved treatment for presymptomatic infantile globoid cell leukodystrophy (GLD [Krabbe disease]). However, correction of disease is not complete, and outcomes remain poor. Herein we evaluated HSCT, intravenous (IV) adeno-associated virus rh10 vector (AAVrh10) gene therapy, and combination HSCT + IV AAVrh10 in the canine model of GLD. While HSCT alone resulted in no increase in survival as compared with untreated GLD dogs (â¼16 weeks of age), combination HSCT + IV AAVrh10 at a dose of 4E13 genome copies (gc)/kg resulted in delayed disease progression and increased survival beyond 1 year of age. A 5-fold increase in AAVrh10 dose to 2E14 gc/kg, in combination with HSCT, normalized neurological dysfunction up to 2 years of age. IV AAVrh10 alone resulted in an average survival to 41.2 weeks of age. In the peripheral nervous system, IV AAVrh10 alone or in addition to HSCT normalized nerve conduction velocity, improved ultrastructure, and normalized GALC enzyme activity and psychosine concentration. In the central nervous system, only combination therapy at the highest dose was able to restore galactosylceramidase activity and psychosine concentrations to within the normal range. These data have now guided clinical translation of systemic AAV gene therapy as an addition to HSCT (NCT04693598, NCT05739643).
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Transplante de Células-Tronco Hematopoéticas , Leucodistrofia de Células Globoides , Cães , Animais , Leucodistrofia de Células Globoides/genética , Leucodistrofia de Células Globoides/terapia , Galactosilceramidase/genética , Psicosina , Transplante de Células-Tronco Hematopoéticas/métodos , Terapia Genética/métodos , Modelos Animais de DoençasRESUMO
To investigate the etiology of multiple primary malignant neoplasms occurred in one patient. Retrospective analysis was performed on a 52-year-old female patient who was admitted to the Department of Endocrinology, the First Affiliated Hospital of Sun Yat-Sen University on October 7, 2021, due to "thyroid occupying lesion for one week". A complete systemic positron emission tomography examination of the patient indicated that the metabolic characteristics of the left thyroid nodules were consistent with medullary thyroid carcinoma, those of the right thyroid nodules were consistent with papillary thyroid carcinoma, and the metabolic characteristics of the T6-7 level were consistent with meningioma, and teratoma was found in the right ovarian region. Intradural subdural mass resection was performed on October 20, 2021, and bilateral total thyroidectomy, isthmus thyroidectomy, bilateral central lymph node dissection and left cervical lymph node dissection were performed on November 2, 2021. The postoperative pathologic diagnosises were meningioma (WHO Grade 1), medullary thyroid carcinoma (left side), and papillary thyroid carcinoma (right side).Whole exon gene sequencing revealed the presence of mutations in the ACAN and FLNB genes, which are associated with dysplasia, as well as mutations in the DDX41 and JAK2 genes, which are linked to active pro-proliferation signaling and tumor susceptibility. In this study, a gene mutation pattern which could lead to multiple primary malignant neoplasms was found.
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Carcinoma Papilar , Neoplasias Meníngeas , Meningioma , Neoplasias Primárias Múltiplas , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/cirurgia , Câncer Papilífero da Tireoide , Meningioma/cirurgia , Estudos Retrospectivos , Tireoidectomia/métodos , Neoplasias Meníngeas/cirurgia , Neoplasias Primárias Múltiplas/cirurgiaRESUMO
Objective: To explore the clinical effects of scalp flaps pedicled with superficial temporal artery parietal branch in repairing facial destructive burn wounds. Methods: A retrospective observational study was conducted. From January 2016 to December 2021, 15 patients with facial destructive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 11 males and 4 females, aged 22 to 79 years. Two patients were complicated with unilateral eyeball destructive burns, two patients were complicated with unilateral auricle defects, eight patients were complicated with lip and cheek defects, and three patients were complicated with lip, cheek, and unilateral nasal alar defects. The burn wound areas ranged from 9 cm×6 cm to 13 cm×10 cm. The scalp flaps pedicled with superficial temporal artery parietal branch, with the area of 10 cm×7 cm to 15 cm×11 cm, were designed, excised, and transferred for repairing burn wounds. The secondary wounds at the donor sites were repaired with medium-thickness scalp grafts. According to patient's needs, the hairs grew at the facial transplanted flap were removed by laser at 2 weeks after the flap was completely viable, or the expanded scalp flap was used to treat the secondary alopecia in the flap donor area of the head at 3 months after the primary wound repair. The survival of the flap/skin graft and the wound healing of the donor and recipient areas after the primary wound repair were recorded. During the follow-up, the appearance of the flap, the scar hyperplasia at the suture site, the repair effect of facial functional parts, the treatment effects of laser hair removal and secondary alopecia treatment at the flap donor site were observed; the patient's satisfaction with the overall repair effect was inquired. Results: After the primary wound repair, all the flaps transplanted to the burn wounds and the skin grafts transplanted to the secondary wounds of the flap donor sites survived well, and the wounds at the donor and recipient sites of flap healed well. The color, texture, and thickness of flap were basically the same as those of normal facial skin, and the scar at the suture site was slight during 3 to 18 months of follow-up period after the primary wound repair. In 11 patients complicated with lip defects, the oral integrity, and the opening and closing functions of mouth were restored with the mouth opening being 2.0-2.5 cm and no microstomia; all the patients could carry out basic language communication, 8 of them could take regular food, and 3 of them could take soft food. The wounds in two patients with unilateral eyeball destructive burns were repaired. In 2 patients complicated with auricle defects, the wounds were repaired, and the external auditory canals were normal. In 3 patients complicated with unilateral nasal alar defects, their noses had poor appearance with reduced nostrils. No hair growth was observed in the facial flap sites after treatment of laser hair removal in 8 patients. Five patients were successfully treated with expanded scalp flaps for secondary alopecia in the flap donor area of the head. The patients were all satisfied with the overall repair effect. Conclusions: The scalp flap pedicled with superficial temporal artery parietal branch has abundant blood supply and is suitable for repairing the wounds in facial destructive burns. It is easy to transfer and can better restore the appearance and function of the recipient area with minimal damage to the flap donor area, which is worthy of clinical promotion.