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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Rearranjo Gênico , Neoplasias de Células Epitelioides Perivasculares , Humanos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/metabolismo , Masculino , Adulto , Pessoa de Meia-Idade , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Diagnóstico Diferencial , Hibridização in Situ Fluorescente , Imuno-HistoquímicaRESUMO
This Letter presents results of a search for the mixing of a sub-eV sterile neutrino with three active neutrinos based on the full data sample of the Daya Bay Reactor Neutrino Experiment, collected during 3158 days of detector operation, which contains 5.55×10^{6} reactor ν[over ¯]_{e} candidates identified as inverse beta-decay interactions followed by neutron capture on gadolinium. The analysis benefits from a doubling of the statistics of our previous result and from improvements of several important systematic uncertainties. No significant oscillation due to mixing of a sub-eV sterile neutrino with active neutrinos was found. Exclusion limits are set by both Feldman-Cousins and CLs methods. Light sterile neutrino mixing with sin^{2}2θ_{14}â³0.01 can be excluded at 95% confidence level in the region of 0.01 eV^{2}â²|Δm_{41}^{2}|â²0.1 eV^{2}. This result represents the world-leading constraints in the region of 2×10^{-4} eV^{2}â²|Δm_{41}^{2}|â²0.2 eV^{2}.
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Degenerative lumbar scoliosis (DLS) is a spinal deformity characterized primarily by abnormal curvature of the lumbar vertebrae, commonly occurring in individuals aged 50 and above. Its pathogenesis involves various factors, including intervertebral disc degeneration, ligament and muscle degradation, as well as genetic and environmental elements. In terms of treatment, non-surgical treatments such as pharmacotherapy, physical therapy, and exercise are regarded as the primary approach. However, for severe cases, individualized surgical intervention is also a viable option, and reasonable classification is the key to surgical decision-making. Current research predominantly emphasizes the osseous structural aspects of the spine, neglecting neural and muscular factors. Future interdisciplinary research is expected to explore more comprehensive and effective treatment modalities, aiding in the restoration of spinal cord function in patients.
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Degeneração do Disco Intervertebral , Vértebras Lombares , Escoliose , Humanos , Escoliose/terapia , Degeneração do Disco Intervertebral/terapiaRESUMO
Objective: To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). Methods: The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. Results: The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (n=4), brachial plexus (n=2) or multiple nerves (n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of ß-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions: NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.
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Coristoma , Fibromatose Agressiva , Mutação , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Fibromatose Agressiva/metabolismo , Fibromatose Agressiva/cirurgia , Masculino , Feminino , Criança , Estudos Retrospectivos , Lactente , Adolescente , Pré-Escolar , Coristoma/patologia , Coristoma/genética , Adulto Jovem , Plexo Braquial/patologia , Plexo Braquial/cirurgia , Nervo Isquiático/patologiaRESUMO
Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.
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Antígenos HLA-B , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais , Transplante Haploidêntico , Humanos , Células Matadoras Naturais/imunologia , Adulto , Feminino , Masculino , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Antígenos HLA-B/genética , Estudos Retrospectivos , Estudos Prospectivos , Doadores de Tecidos , Criança , Alelos , Pré-Escolar , Condicionamento Pré-Transplante/métodosRESUMO
Lushan Yunwu tea quality is limited by soil acidity and sterility. This article examined a 3-year localization experiment at 1100 m altitude to demonstrate the sustainable management of conditioners, calcium magnesium phosphate (P), rapeseed cake (C), and combination application (P + C) by one-time application on the soil-tea system in Mount Lushan. The study found that conditioners (P, C, P + C) reduced soil acidification and maintained a pH of 4.75-5.34, ideal for tea tree development for 3 years. Phosphorus activation coefficient (PAC), nitrogen activation coefficient (NAC), and organic matter (OM) content were significantly higher (P < 0.05) in the first year after conditioner treatment, with P + C being the best. After P + C, PAC, NAC, and OM rose by 31.25%, 47.70%, and 10.06 g kg-1 compared to CK. In comparison to the CK, tea's hundred-bud weight (BW), free amino acids (AA), tea polyphenols (TPC), and chlorophyll (Chl) content of P + C treatment got 29.98%, 14.41%, 22.49%, and 28.85% increase compared to that of the CK, respectively. In the second year, the three treatments of P, C and P + C still had significant moderating effects on the physicochemical properties of the soil and the quality indexes of the tea leaves. The PAC of the soil under the three treatments increased by 0.06%, 0.07% and 0.18%, respectively, as compared to the control.P + C increased BW, AA, TPC and Chl of tea for 2 years. Three conditioners had 2-year regulatory impacts on soil fertility indicators, tea output, and quality. C and P + C both increased soil OM by 18.59% and 21.78% compared to CK in the third year, outperforming P treatment. Redundancy analysis revealed that the primary physicochemical factors influencing tea output and quality were soil OM and pH, with available phosphorus, urease, acid phosphatase, and available nitrogen following closely afterwards.
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Solo , Solo/química , China , Chá/química , Camellia sinensis/química , Concentração de Íons de Hidrogênio , Fertilizantes , Brassica rapa , Fosfatos , Nitrogênio , Clorofila , Fósforo/análiseRESUMO
BACKGROUND: Limited evidence exists on the economic burden of individuals who progress from mild cognitive impairment (MCI) to Alzheimer disease and related dementia disorders (ADRD). OBJECTIVES: To assess the all-cause health care resource utilization and costs for individuals who develop ADRD following an MCI diagnosis compared to those with stable MCI. DESIGN: This was a retrospective cohort study from January 01, 2014, to December 31, 2019. SETTING: The Merative MarketScan Commercial and Medicare Databases were used. PARTICIPANTS: Individuals were included if they: (1) were aged 50 years or older; (2) had ≥1 claim with an MCI diagnosis based on the International Classification of Diseases, Ninth Revision (ICD-9) code of 331.83 or the Tenth Revision (ICD-10) code of G31.84; and had continuous enrollment. Individuals were excluded if they had a diagnosis of Parkinson's disease or ADRD or prescription of ADRD medication. MEASUREMENTS: Outcomes included all-cause utilization and costs per patient per year in the first 12 months following MCI diagnosis, in total and by care setting: inpatient admissions, emergency department (ED) visits, outpatient visits, and pharmacy claims. RESULTS: Out of the total of 5185 included individuals, 1962 (37.8%) progressed to ADRD (MCI-to-ADRD subgroup) and 3223 (62.2%) did not (Stable MCI subgroup). Adjusted all-cause utilization was higher for all care settings in the MCI-to-ADRD subgroup compared with the Stable MCI subgroup. Adjusted all-cause mean total costs ($34 599 vs $24 541; mean ratio [MR], 1.41 [95% CI, 1.31-1.51]; P<.001), inpatient costs ($47 463 vs $38 004; MR, 1.25 [95% CI, 1.08-1.44]; P=.002), ED costs ($4875 vs $3863; MR, 1.26 [95% CI, 1.11-1.43]; P<.001), and outpatient costs ($16 652 vs $13 015; MR, 1.28 [95% CI, 1.20-1.37]; P<.001) were all significantly higher for the MCI-to-ADRD subgroup compared with the Stable MCI subgroup. CONCLUSIONS: Individuals who progressed from MCI to ADRD had significantly higher health care costs than individuals with stable MCI. Early identification of MCI and delaying its progression is important to improve patient and economic outcomes.
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Doença de Alzheimer , Disfunção Cognitiva , Progressão da Doença , Humanos , Doença de Alzheimer/economia , Disfunção Cognitiva/economia , Disfunção Cognitiva/diagnóstico , Masculino , Feminino , Estados Unidos , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso de 80 Anos ou mais , Medicare/economia , Efeitos Psicossociais da DoençaRESUMO
Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease's characteristics and antiviral treatment strategies, are discussed here.
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Antivirais , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Tolerância Imunológica , Hepatite B/tratamento farmacológicoAssuntos
Tumor do Seio Endodérmico , Neoplasias do Mediastino , Derrame Pleural Maligno , alfa-Fetoproteínas , Humanos , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/metabolismo , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/metabolismo , Adulto , Estudos Retrospectivos , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/diagnóstico , Adulto Jovem , alfa-Fetoproteínas/metabolismo , Queratinas/metabolismo , Diagnóstico Diferencial , Fatores de Transcrição/metabolismo , Glipicanas/metabolismo , Fosfatase Alcalina/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Erros de Diagnóstico , Imunofenotipagem , Isoenzimas , Proteínas Ligadas por GPIRESUMO
Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1ß, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1ß treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress-related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1ß-induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1ß-induced TFRC expression, while inhibition of TFRC did not downregulate IL-1ß-induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1ß-induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1ß-inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.
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Condrócitos , Ferroptose , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-1beta , Osteoartrite , Estresse Oxidativo , Receptores da Transferrina , Transtornos da Articulação Temporomandibular , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Receptores da Transferrina/metabolismo , Osteoartrite/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Masculino , Humanos , Ratos Sprague-Dawley , Inflamação , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Cicloexilaminas/farmacologia , Cartilagem Articular/metabolismo , Colágeno Tipo II , Espécies Reativas de Oxigênio/metabolismo , Feminino , Aldeídos , FenilenodiaminasRESUMO
AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Imageamento por Ressonância Magnética , Humanos , Colangiocarcinoma/diagnóstico por imagem , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , AdultoRESUMO
Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.
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Erros Inatos do Metabolismo dos Aminoácidos , Mutação , Humanos , Masculino , Feminino , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Adolescente , Estudos Retrospectivos , Criança , Seguimentos , Idade de Início , Fenótipo , Genótipo , Prognóstico , Ácido Metilmalônico/sangue , Vitamina B 12 , OxirredutasesAssuntos
Proteínas Correpressoras , Ciclina B , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Sarcoma , Humanos , Masculino , Ciclina B/genética , Ciclina B/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sarcoma/genética , Sarcoma/patologia , Sarcoma/metabolismo , Hibridização in Situ Fluorescente , Diagnóstico Diferencial , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/metabolismo , Imuno-Histoquímica , Adulto , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismoRESUMO
Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.
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Neoplasias Ósseas , Rearranjo Gênico , Hibridização in Situ Fluorescente , Proteína EWS de Ligação a RNA , Neoplasias de Tecidos Moles , Humanos , Proteína EWS de Ligação a RNA/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/diagnóstico , Hibridização in Situ Fluorescente/métodos , Neoplasias Ósseas/genética , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/diagnóstico , Histiocitoma Fibroso Maligno/patologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/diagnósticoRESUMO
OBJECTIVE: To evaluate the vaccine effectiveness (VE) of mRNA COVID-19 vaccines in children using a meta-analysis approach. MATERIALS AND METHODS: Relevant studies on the use of mRNA COVID-19 vaccines in children were identified through computerized searches. VE-related indicators were extracted, and data analysis was performed using the R software with the meta-package. RESULTS: This study included a total of 12 relevant articles involving 9,963,732 participants from multiple centers in different countries, including the United States, Canada, Singapore, Israel, South Korea, and Qatar. The administered vaccine types included BNT162b2 and mRNA-1273. Participants were categorized into partially immunized (one dose of vaccine) and fully immunized (two doses of vaccine). Four articles reported VE after one dose of vaccine, while 12 reported VE after two doses. Heterogeneity analysis indicated significant heterogeneity among the studies, warranting the use of a random-effects model for analysis. Meta-analysis results revealed that the VE of partial immunization ranged from 16.61 (95% CI: 6.32-25.77) to 34.30 (95% CI: 24.21-43.04), with a pooled VE of 22.80 (95% CI: 15.68-29.32). The VE after full immunization ranged from 16.14 (95% CI: 14.42-17.83) to 90.47 (95% CI: 67.42-97.21), with a pooled VE of 56.17 (95% CI: 41.12-67.37). Meta-regression analysis showed no statistically significant correlation between VE and time (p>0.05). CONCLUSIONS: Both partial and full immunization of the BNT162b2 mRNA vaccine provide benefits in reducing infection rates. VE varies over time and is closely associated with viral mutations and waning immunity. The specific mechanisms require further investigation.
Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Eficácia de Vacinas , Humanos , Criança , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/administração & dosagem , SARS-CoV-2/imunologia , Vacinas de mRNARESUMO
BACKGROUND: Screening tools such as calf circumference (CC) and Yubi-wakka (finger-ring) test have been recognized as effective tools by Asian Working Group for Sarcopenia 2019 (AWGS'19) for sarcopenia screening but their comparative agreement, diagnostic performance and validity are unclear. OBJECTIVES: This study aims to determine: (i)agreement between calf and finger-ring circumference, (ii)diagnostic performance for low muscle mass and AWGS'19 sarcopenia diagnosis, (iii)correlation with muscle mass, strength, and physical performance, and (iv)association with frailty, life space mobility and physical activity. METHODS: We studied 187 healthy community-dwelling older adults (mean age=66.8+7.0years) from the GERILABS-2 study. CC was measured via (i) both calves in sitting and standing positions, and (ii) Yubi-wakka test by encircling the thickest part of the non-dominant calf with index fingers and thumbs of both hands. We performed Cohen's kappa to check for agreement, area under receiver operating characteristic curve (AUC) to compare diagnostic performance, partial correlations adjusted for age and gender to compare convergent validity, and logistic regression to determine predictive validity for outcome measures. RESULTS: Sarcopenia prevalence was 24.0% (AWGS'19). Yubi-wakka identified 16.6% of participants as screen-positive ("smaller"), showing moderate agreement only with non-dominant sitting CC measurements (k=0.421,p<0.001) and having lower diagnostic performance in determining low muscle mass (AUC=0.591 vs 0.855-0.870,p<0.001; sensitivity=57.1% vs 75.5-90.8%; specificity=58.4% vs 70.8-80.9%) and sarcopenia diagnosis (AUC=0.581 vs 0.788-0.818,p<0.001; sensitivity=55.6% vs 57.5-71.8%; specificity=74.4% vs 75.6-88.9%) compared to CC measurements. Yubi-wakka correlated significantly with muscle mass, grip strength and knee extension but not physical performance. When adjusted for age, gender and hypertension, Yubi-wakka was significantly associated with frailty (OR=3.96,95%CI:1.09-14.38), life space mobility (OR=2.38,95%CI:1.08-5.24) and physical activity (OR=2.50,95%CI:1.07-5.86). DISCUSSION AND CONCLUSIONS: Yubi-wakka provides a self-administered, low-cost and practicable community screening tool for sarcopenia. Our study affirmed the convergent and predictive validity of Yubi-wakka, albeit with lower sensitivity and specificity in diagnostic performance compared to CC measurements.
Assuntos
Fragilidade , Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Articulação do Joelho , Exercício Físico , Força da MãoRESUMO
OBJECTIVE: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). PATIENTS AND METHODS: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. RESULTS: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. CONCLUSIONS: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.
Assuntos
Pancreatite , Humanos , Pancreatite/diagnóstico , Estudos Retrospectivos , Doença Aguda , Prognóstico , Biomarcadores , Curva ROC , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease (CHD). METHODS: We analyzed the data of 226 patients undergoing coronary artery angiography (CAG) in our hospital between October, 2021 and October, 2022, including 47 patients with normal CAG findings (control group) and 179 patients with mild, moderate or severe coronary artery stenosis (CHD group). Serum FDX1 and LA levels were determined with ELISA for all the patients. We also examined pathological changes in the aorta of normal and ApoE-/- mice using HE staining and observed collagen fiber deposition with Sirius red staining. Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta, and RT-PCR was performed to detect the expressions of FDX1, LIAS and ACO2 mRNAs in the myocardial tissues. RESULTS: Compared with the control patients, CHD patients had significantly lower serum FDX1 and LA levels, which decreased progressively as coronary artery stenosis worsened (P < 0.01) and as the number of involved coronary artery branches increased (P < 0.05). Serum FDX1 and LA levels were positively correlated (r=0.451, P < 0.01) and they both negatively correlated with the Gensini score (r=-0.241 and -0.273, respectively; P < 0.01). Compared with normal mice, ApoE-/- mice showed significantly increased lipid levels (P < 0.01) and atherosclerosis index, obvious thickening, lipid aggregation, and collagen fiber hyperplasia in the aorta, and significantly reduced expressions of FDX1, LA, LIAS, and ACO2 (P < 0.05). CONCLUSION: Serum FDX1 and LA levels decrease with worsening of coronary artery lesions, and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.