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Upper aerodigestive squamous cell carcinoma (UASCC) is a common and aggressive malignancy with few effective therapeutic options. Here, we investigate amino acid metabolism in this cancer, surprisingly noting that UASCC exhibits the highest methionine level across all human cancers, driven by its transporter LAT1. We show that LAT1 is also expressed at the highest level in UASCC, transcriptionally activated by UASCC-specific promoter and enhancers, which are directly coregulated by SCC master regulators TP63/KLF5/SREBF1. Unexpectedly, unbiased bioinformatic screen identifies EZH2 as the most significant target downstream of the LAT1-methionine pathway, directly linking methionine metabolism to epigenomic reprogramming. Importantly, this cascade is indispensable for the survival and proliferation of UASCC patient-derived tumor organoids. In addition, LAT1 expression is closely associated with cellular sensitivity to inhibition of the LAT1-methionine-EZH2 axis. Notably, this unique LAT1-methionine-EZH2 cascade can be targeted effectively by either pharmacological approaches or dietary intervention in vivo. In summary, this work maps a unique mechanistic cross talk between epigenomic reprogramming with methionine metabolism, establishes its biological significance in the biology of UASCC, and identifies a unique tumor-specific vulnerability which can be exploited both pharmacologically and dietarily.
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Carcinoma de Células Escamosas , Regulação Neoplásica da Expressão Gênica , Transportador 1 de Aminoácidos Neutros Grandes , Metionina , Metionina/metabolismo , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linhagem Celular Tumoral , Epigênese Genética , Epigenômica/métodos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Proliferação de Células , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Reprogramação Celular/genéticaRESUMO
Paroxysmal nocturnal haemoglobinuria (PNH) is a disorder resulting from erythrocyte membrane deficiencies caused by PIG-A gene mutations. While current treatments alleviate symptoms, they fail to address the underlying cause of the disease-the pathogenic PNH clones. In this study, we found that the expression of carbamoyl phosphate synthetase 1 (CPS1) was downregulated in PNH clones, and the level of CPS1 was negatively correlated with the proportion of PNH clones. Using PIG-A knockout K562 (K562 KO) cells, we demonstrated that CPS1 knockdown increased cell proliferation and altered cell metabolism, suggesting that CPS1 participates in PNH clonal proliferation through metabolic reprogramming. Furthermore, we observed an increase in the expression levels of the histone demethylase JMJD1C in PNH clones, and JMJD1C expression was negatively correlated with CPS1 expression. Knocking down JMJD1C in K562 KO cells upregulated CPS1 and H3K36me3 expression, decreased cell proliferation and increased cell apoptosis. Chromatin immunoprecipitation analysis further demonstrated that H3K36me3 regulated CPS1 expression. Finally, we demonstrated that histone demethylase inhibitor JIB-04 can suppressed K562 KO cell proliferation and reduced the proportion of PNH clones in PNH mice. In conclusion, aberrant regulation of the JMJD1C-H3K36me3-CPS1 axis contributes to PNH clonal proliferation. Targeting JMJD1C with a specific inhibitor unveils a potential strategy for treating PNH patients.
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Proliferação de Células , Hemoglobinúria Paroxística , Histona Desmetilases com o Domínio Jumonji , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Animais , Camundongos , Células K562 , Hemoglobinúria Paroxística/patologia , Hemoglobinúria Paroxística/genética , Hemoglobinúria Paroxística/metabolismo , Masculino , Feminino , Apoptose , Reprogramação Metabólica , Oxirredutases N-DesmetilantesRESUMO
The seawater refractive index is an essential parameter in ocean observation, making its high-precision measurement necessary. This can be effectively achieved using a position-sensitive detector-based measurement system. However, in the actual measurement process, the impact of the jitter signal measurement error on the results cannot be ignored. In this study, we theoretically analysed the causes of long jitter signals during seawater refractive index measurements and quantified the influencing factors. Through this analysis, it can be seen that the angle between the two windows in the seawater refractive index measurement area caused a large error in the results, which could be effectively reduced by controlling the angle to within 2.06°. At the same time, the factors affecting the position-sensitive detector's measurement accuracy were analysed, with changes to the background light, the photosensitive surface's size, and the working environment's temperature leading to its reduction. To address the above factors, we first added a 0.9 nm bandwidth, narrow-band filter in front of the detector's photosensitive surface during system construction to filter out any light other than that from the signal light source. To ensure the seawater refractive index's measuring range, a position-sensitive detector with a photosensitive surface size of 4 mm × 4 mm was selected; whereas, to reduce the working environment's temperature variation, we partitioned the measurement system. To validate the testing error range of the optimised test system, standard seawater samples were measured under the same conditions, showing a reduction in the measurement system's jitter signal from 0.0022 mm to 0.0011 mm, before and after optimisation, respectively, as well as a reduction in the refractive index's deviation. The experimental results show that the refractive index of seawater was effectively reduced by adjusting the measurement system's optical path and structure.
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The refractive index of seawater is one of the essential parameters in ocean observation, so it is necessary to achieve high-precision seawater refractive index measurements. In this paper, we propose a method for measuring the refractive index of seawater, based on a position-sensitive detector (PSD). A theoretical model was established to depict the correlation between laser spot displacement and refractive index change, utilizing a combination of a position-sensitive detector and laser beam deflection principles. Based on this optical measurement method, a seawater refractive index measurement system was established. To effectively enhance the sensitivity of refractive index detection, a focusing lens was incorporated into the optical path of the measuring system, and simulations were conducted to investigate the impact of focal length on refractive index sensitivity. The calibration experiment of the measuring system was performed based on the relationship between the refractive index of seawater and underwater pressure (depth). By measuring laser spot displacement at different depths, changes in displacement, with respect to both refractive index and depth, were determined. The experimental results demonstrate that the system exhibits a sensitivity of 9.93×10-9 RIU (refractive index unit), and the refractive index deviation due to stability is calculated as ±7.54×10-9 RIU. Therefore, the feasibility of this highly sensitive measurement of seawater refractive index is verified. Since the sensitivity of the refractive index measurement of this measurement system is higher than the refractive index change caused by the wake of underwater vehicles, it can also be used in various applications for underwater vehicle wake measurement, as well as seawater refractive index measurement, such as the motion state monitoring of underwater navigation targets such as AUVs and ROVs.
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Seawater density is an important physical property in oceanography that affects the accuracy of calculations such as gravity fields and tidal potentials and the calibration of acoustic and optical oceanographic sensors. In related studies, constant density values are frequently used, which can introduce significant errors. Therefore, this study employs a basic convolutional neural network model to construct a comprehensive model showing the seawater density distribution across the globe. The model takes into account depth, latitude, longitude, and month as inputs. Numerous real seawater datasets were used to train the model, and it has been shown that the model has an absolute mean error and root mean square error of less than 1 kg/m3 in 99% of the test set samples. The model effectively demonstrates the influence of input parameters on the distribution of seawater density. In this paper, we present a newly developed global model for distributing seawater density which is both comprehensive and accurate, surpassing previous models. The utilization of the model presented in this paper for estimating seawater density can minimize errors in theoretical ocean models and serve as a foundation for designing and analyzing ocean exploration systems.
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Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with ßCD41-42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with ß-thalassemia intermedia and a lethal fetus with Hb Bart's hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.
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Variações do Número de Cópias de DNA , Talassemia , Humanos , Variações do Número de Cópias de DNA/genética , alfa-Globinas/genética , Cromossomos Humanos Par 16/genética , Talassemia/genética , Família MultigênicaRESUMO
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cells (HSCs). Long noncoding RNAs (lncRNAs) perform a wide range of biological functions, including the regulation of gene expression, cell differentiation, and proliferation, but their role in PNH remains unclear.CD59- and CD59+ granulocytes and monocytes from 35 PNH patients were sorted. High-throughput sequencing was analyzed in 5 PNH patients, and differentially expressed lncRNAs and mRNAs were identified. The mRNAs with fragments per kilobase of exon model per million mapped fragments (FPKM) > 10 in at least 3 patients were selected, and experiments were performed to identify their upstream regulatory lncRNAs. The expression of selected mRNAs and lncRNAs was verified by qRTâPCR, and the correlation of these expression patterns with clinical data from other 30 PNH patients was analyzed. Then, the functions of the lncRNAs were studied in the PIGA-KO-THP-1 cell line.Transcription analysis revealed 742 upregulated and 1376 downregulated lncRNAs and 3276 upregulated and 213 downregulated mRNAs. After deep screening, 8 highly expressed mRNAs that were related to the NF-κB pathway were analyzed to determine coexpression patterns. LINC01002, FAM157C, CTD-2530H12.2, XLOC-064331 and XLOC-106677 were correlated with the 8 mRNAs. After measuring the expression of these molecules in 30 PNH patients by qRTâPCR, lncRNA FAM157C was verified to be upregulated in the PNH clone, and its expression levels were positively correlated with the LDH levels and CD59- granulated and monocyte cell ratios. After knockdown of the FAM157C gene in the PIGA-KO-THP-1 cell line, we found that the cells were arrested in the G0/G1 phase and S phase, the apoptosis rate increased, and the cell proliferation decreased.LncRNA FAM157C was proven to promote PNH clone proliferation, and this is the first study to explore the role of lncRNAs in PNH.
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Hemoglobinúria Paroxística , RNA Longo não Codificante , Humanos , Hemoglobinúria Paroxística/genética , Hemoglobinúria Paroxística/diagnóstico , RNA Longo não Codificante/genética , Células-Tronco Hematopoéticas/metabolismo , Células Clonais/química , Antígenos CD59/análise , Antígenos CD59/metabolismo , Proliferação de Células/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Watermelon frost, a traditional Chinese medicine produced using watermelon and Glauber's salt, has been widely used for the therapy of oral and throat disorders. Watermelon contains various phytochemical compounds including cucurbitacins and their glycoside derivatives, which have attracted considerable attention because of their medicinal values. However, whether the composition of cucurbitacins existed in watermelon frost was rarely reported. In this study, three cucurbitacins including cucurbitacin B, isocucurbitacin B, and cucurbitacin E were found from watermelon frost extract assisted by ultra-high-performance liquid chromatography-tandem mass spectrometry and molecular networking guided strategy, and the compounds were verified using standard solutions. Furthermore, a quantification method for simultaneously targeted analysis of cucurbitacins was established using ultra-high-performance liquid chromatography-tandem mass spectrometry operating in the multiple reaction monitoring mode. Among them, cucurbitacin B and cucurbitacin E in watermelon frost samples were determined, and the concentrations were 3.78 ± 0.18 and 0.86 ± 0.19 ng/ml, respectively. While isocucurbitacin B was not detected due to the lower content possibly. In conclusion, ultra-high-performance liquid chromatography-tandem mass spectrometry combined with molecular networking is a very useful technique for the rapid identification of unknown cucurbitacin components in watermelon frost.
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Citrullus , Cucurbitacinas , Cromatografia Líquida de Alta Pressão/métodos , Citrullus/química , Espectrometria de Massas em Tandem/métodosRESUMO
BACKGROUND: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. METHODS: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. RESULTS: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. CONCLUSIONS: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.
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Síndrome de Down , Gestantes , Feminino , Gravidez , Humanos , Laboratórios Clínicos , Diagnóstico Pré-Natal/métodos , Síndrome de Down/diagnóstico , Aneuploidia , Resultado da GravidezRESUMO
The refractive index measurement of seawater has proven significance in oceanography, while an optical heterodyne interferometer is an important, highly accurate, tool used for seawater refractive index measurement. However, for practical seawater refractive index measurement, the refractive index of seawater needs to be monitored for long periods of time, and the influence of drift error on the measurement results for these cases cannot be ignored. This paper proposes a drift error compensation algorithm based on wavelet decomposition, which can adaptively separate the background from the signal, and then calculate the frequency difference to compensate for the drift error. It is suitable for unstable signals, especially signals with large differences between the beginning and the end, which is common in actual seawater refractive index monitoring. The authors identify that the primary cause of drift error is the frequency instability of the acousto-optic frequency shifter (AOFS), and the actual frequency difference was measured through experimentation. The frequency difference was around 0.1 Hz. Simulation experiments were designed to verify the effectiveness of the algorithm, and the standard deviation of the optical length of the results was on the scale of 10-8 m. Liquid refractive index measurement experiments were carried out in a laboratory, and the measurement error was reduced from 36.942% to 0.592% after algorithm processing. Field experiments were carried out regarding seawater refractive index monitoring, and the algorithm-processing results are able to match the motion of the target vehicle. The experimental data were processed with different algorithms, and, according to the comparison of the results, the proposed algorithm performs better than other existing drift error elimination algorithms.
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AIMS: This study aimed to investigate the physiological responses of two gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and two gram-positive bacteria (Enterococcus faecalis and Bacillus sphaericus) to ultraviolet (UV) and chlorine disinfection. METHODS AND RESULTS: Bacterial inactivation by UV and chlorine disinfection were evaluated with a plate count method for culturability, FCM and PMA-qPCR for membrane integrity and DyeTox13-qPCR for enzymatic activity, respectively. Both UV and chorine disinfection caused complete loss of culturability while membrane integrity remained intact after UV disinfection. Both DyeTox13-qPCR and PMA-qPCR showed high ΔCt values up to 8.9 after chlorine disinfection, indicating that both methods were able to distinguish non-treated from chlorine-treated cells. Although PMA-qPCR could not differentiate membrane integrity of cells on UV exposure, DyeTox13-qPCR showed significant differences in ΔCt values of 5.05 and 10.4 for gram-negative (E. coli) and gram-positive (Enterococcus) bacteria, respectively. However, DyeTox13-qPCR for gram-negative bacteria displayed relatively small differences in ΔCt values compared with gram-positive bacteria. CONCLUSION: UV and chlorine disinfection led to changes in physiological state of gram-negative and gram-positive bacteria. Particularly, UV disinfection could induce active but non-culturable (ABNC) for gram-negative bacteria and dormant cell for gram-positive bacteria where intact cells no longer showed the enzymatic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: UV and chlorine are commonly used to disinfect water, food and fomites to inactivate pathogenic bacteria. However, a viable but non-culturable (VBNC) state of bacteria induced by disinfection may underestimate the health risks because of the potential resuscitation of VBNC cells. This study highlighted that bacteria could undergo different physiological (ABNC or dormant) states during UV and chlorine disinfection. In addition, viability PCR techniques could provide insight into the changes in physiological states during disinfection processes.
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Cloro , Desinfecção , Bactérias/genética , Cloro/farmacologia , Desinfecção/métodos , Escherichia coli , Citometria de Fluxo , Viabilidade Microbiana , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
Diarrheal diseases caused by Salmonella pose a major threat to public health, and assessment of bacterial viability is critical in determining the safety of food and drinking water after disinfection. Viability PCR could overcome the limitations of traditional culture-dependent methods for a more accurate assessment of the viability of a microbial sample. In this study, the physiological changes in Salmonella Typhimurium induced by pasteurization and UV treatment were evaluated using a culture-based method, RT-qPCR, and viability PCR. The plate count results showed no culturable S. Typhimurium after the pasteurization and UV treatments, while viability PCR with propidium monoazide (PMA) and DyeTox13-qPCR indicated that the membrane integrity of S. Typhimurium remained intact with no metabolic activity. The RT-qPCR results demonstrated that invasion protein (invA) was detectable in UV-treated cells even though the log2-fold change ranged from - 2.13 to - 5.53 for PMA treatment. However, the catalytic activity gene purE was under the detection limit after UV treatment, indicating that most Salmonella entered metabolically inactive status after UV disinfection. Also, viability PCRs were tested with artificially contaminated eggs to determine physiological status on actual food matrices. DyeTox13-qPCR methods showed that most Salmonella lost their metabolic activity but retained membrane integrity after UV disinfection. RT-qPCR may not determine the physiological status of Salmonella after UV disinfection because mRNA could be detectable in UV-treated cells depending on the choice of target gene. Viability PCR demonstrated potential for rapid and specific detection of pathogens with physiological states such as membrane integrity and metabolic activity.Key Points⢠Membrane integrity of Salmonella remained intact with no metabolic activity after UV.⢠mRNA could be detectable in UV-treated cells depending on the choice of target gene.⢠Viability PCR could rapidly detect specific pathogens with their physiological states.
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Azidas , Salmonella typhimurium , Azidas/farmacologia , Viabilidade Microbiana , Pasteurização , Propídio/análogos & derivados , Propídio/metabolismo , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real/métodos , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMO
Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and adolescents carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC 'trio' constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, directly establishes super-enhancers of each of these three TFs to activate their transcription. In turn, KLF15, TCF4 and NKX2-2 co-bind to their own and each other's super-enhancers and promoters, forming an inter-connected auto-regulatory loop. Functionally, CRC factors contribute significantly to cell proliferation of Ewing sarcoma both in vitro and in vivo. Mechanistically, CRC factors exhibit prominent capacity of co-regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enhancers genome-wide. Downstream, CRC TFs coordinately regulate gene expression networks in Ewing sarcoma, controlling important signaling pathways for cancer, such as lipid metabolism pathway, PI3K/AKT and MAPK signaling pathways. Together, molecular characterization of the oncogenic CRC model advances our understanding of the biology of Ewing sarcoma. Moreover, CRC-downstream genes and signaling pathways may contain potential therapeutic targets for this malignancy.
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Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Metabolismo dos Lipídeos/genética , Camundongos Nus , Proteínas Nucleares , Proteínas de Fusão Oncogênica/fisiologia , Proteína Proto-Oncogênica c-fli-1/fisiologia , Proteína EWS de Ligação a RNA/fisiologia , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Transdução de Sinais , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Fatores de Transcrição , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
BACKGROUND: We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of 20 refractory/recurrent PNH patients, including the clinical efficacy of chemotherapy treatment, safety, and survival. METHODS: The clinical data of 20 classic PNH patients who were refractory/recurrent or had glucocorticoid dependence in our hospital were analyzed, including clinical manifestations, laboratory examinations, treatment efficacy, and survival. RESULTS: Seventeen patients had a marked improvement in anemia after chemotherapy, 14 patients acquired blood transfusion independence, and the Hb of 3 patients increased to normal levels. Although 6 patients still needed blood transfusion, the transfusion interval was significantly prolonged. The percentages of LDH, TBIL, and RET, which are indicators of hemolysis, were significantly lower than those before chemotherapy. The dosage of adrenal glucocorticoids was reduced by more than half compared with that before chemotherapy. CONCLUSIONS: Chemotherapy can reduce PNH clones, promote normal hematopoiesis, and control hemolytic attack. It is a promising and widely used therapeutic method.
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Citarabina , Daunorrubicina , Glucocorticoides , Hemoglobinúria Paroxística , Metilprednisolona , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Citarabina/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada/efeitos adversos , Glucocorticoides/administração & dosagem , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/mortalidade , Metilprednisolona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Daunorrubicina/administração & dosagemRESUMO
BACKGROUND: Temporal hollowing is an early sign of aging, and many techniques comprising the injection of fillers into the temporal fossa to correct this hollowing have been described. OBJECTIVE: To assess the safety of a new technique in which stromal vascular fraction gel is used for temporal hollowing. METHODS: Thirty-three patients with temporal hollowing were corrected with the aforementioned gel using deep injection and shallow pave filling at the Department of Plastic and Reconstructive Surgery, Guangdong Women and Children Hospital, China, between January 2017 and April 2021. This gel was injected into the double plane via a needle and cannula by the same cutaneous access points to prevent severe vascular injury. Improvement was evaluated by self-assessment, the Hollowness Severity Rating Scale (grade range, 0-3; lower grades represent minimal hollowness), and a satisfaction survey. RESULTS: Self-assessment questionnaire (6 questions) results were satisfactory; 44 temples (67%) demonstrated more than 2 grades of magnitude of clinical improvement. Thirty-one patients (94%) were satisfied with their outcomes; the complaint ratio was low. CONCLUSION: The high satisfaction rate of patients treated using the stromal vascular fraction gel by deep injection and shallow pave filling suggests that this technique is simple, effective, and safe. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Fração Vascular Estromal , Cadáver , China , Feminino , Humanos , Injeções , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Little is known about whether the influence of glycemic variability on arrhythmia is related to age in type 2 diabetes mellitus (T2DM). Therefore, we aimed to compare the association between glycemic variability and arrhythmia in middle-aged and elderly T2DM patients. METHODS: A total of 107 patients were divided into two groups: elderly diabetes mellitus group (EDM, n = 73) and middle-aged diabetes mellitus group (MDM, n = 34). The main clinical data, continuous glucose monitoring (CGM) and dynamic ECG reports were collected. The parameters including standard deviation of blood glucose (SDBG), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), absolute means of daily differences (MODD), time in range (TIR), time below range (TBR), time above range (TAR), coefficient of variation (CV) were tested for glycemic variability evaluation. RESULTS: In terms of blood glucose fluctuations, MAGE (5.77 ± 2.16 mmol/L vs 4.63 ± 1.89 mmol/L, P = 0.026), SDBG (2.39 ± 1.00 mmol/L vs 2.00 ± 0.82 mmol/L, P = 0.048), LAGE (9.53 ± 3.37 mmol/L vs 7.84 ± 2.64 mmol/L, P = 0.011) was significantly higher in EDM group than those of MDM group. The incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat were significantly higher in EDM group compared with the MDM group (all P < 0.05). Among patients with hypoglycemia events, the incidences of atrial premature beat, couplets of atrial premature beat, atrial tachycardia and ventricular premature beat (all P < 0.05) were significantly higher in the EDM group than those in the MDM group. In EDM group, TIR was negatively correlated with atrial tachycardia in the MAGE1 layer and with atrial tachycardia and ventricular premature beat in the MAGE2 layer, TBR was significantly positively correlated with atrial tachycardia in the MAGE2 layer (all P < 0.05). In MDM group, TAR was positively correlated with ventricular premature beat and atrial tachycardia in the MAGE2 layer (all P < 0.05). CONCLUSIONS: The study demonstrated the elderly patients had greater glycemic variability and were more prone to arrhythmias. Therefore, active control of blood glucose fluctuation in elderly patients will help to reduce the risk of severe arrhythmia.
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Arritmias Cardíacas/etiologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/fisiologia , Arritmias Cardíacas/sangue , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Glicemia/fisiologia , Automonitorização da Glicemia , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Ischemic postconditioning (PostC) conventionally refers to a series of brief blood vessel occlusions and reperfusions, which can induce an endogenous neuroprotective effect and reduce cerebral ischemia/reperfusion (I/R) injury. Depending on the site of adaptive ischemic intervention, PostC can be classified as in situ ischemic postconditioning (ISPostC) and remote ischemic postconditioning (RIPostC). Many studies have shown that ISPostC and RIPostC can reduce cerebral IS injury through protective mechanisms that increase cerebral blood flow after reperfusion, decrease antioxidant stress and anti-neuronal apoptosis, reduce brain edema, and regulate autophagy as well as Akt, MAPK, PKC, and KATP channel cell signaling pathways. However, few studies have compared the intervention methods, protective mechanisms, and cell signaling pathways of ISPostC and RIPostC interventions. Thus, in this article, we compare the history, common intervention methods, neuroprotective mechanisms, and cell signaling pathways of ISPostC and RIPostC.
Assuntos
Encéfalo/irrigação sanguínea , Pós-Condicionamento Isquêmico/métodos , Neuroproteção , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVES: To investigate the relationship between immune status and paroxysmal nocturnal hemoglobinuria (PNH) clonal evolution of severe aplastic anemia (SAA) patients who received anti-human thymocyte globulin (ATG) treatment. METHODS: The clinical data of 102 SAA patients who received ATG were collected and retrospectively analyzed. The remission rate, remission time, response rate, hematopoietic, and immune status were compared. Malignant clones were also observed. RESULTS: The remission rate of the group with PNH clones appeared after treatment was significantly higher than the group without PNH clones. The response rate at 12 months of the groups with PNH clones was significantly higher than the group without PNH clones. The recovery of Hb and Ret % of patients with PNH clones was earlier than the patients without PNH clones. The reduction of percentage of CD8+ HLA-DR+ /CD8+ and Th1/Th2 ratio of patients with PNH clones was both earlier than the patients without PNH clones. Six patients developed myelodysplastic syndromes (MDS). CONCLUSION: In SAA patients with PNH clones, the cytotoxic T-cell function and Th1 cell number recovered more quickly and had better response to IST. A small number of SAA patients with or without PNH clones developed MDS malignant clones.
Assuntos
Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/imunologia , Soro Antilinfocitário/uso terapêutico , Hemoglobinúria Paroxística/imunologia , Adolescente , Adulto , Idoso , Anemia Aplástica/sangue , Linfócitos T CD8-Positivos , Criança , Ciclosporina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of Chinese paroxysmal nocturnal hemoglobinuria (PNH) patients, and assessed the efficacy and safety of glucocorticoid in PNH patients. METHODS: The clinical data of 92 PNH cases in our hospital were analyzed, including clinical manifestation, laboratory examination, treatment efficacy, and survival. RESULTS: The main clinical manifestations of these patients included hemoglobinuria, anemia, fatigue, dyspnea, headache, abdominal pain, and erectile dysfunction. Glucocorticoid is still the first-line treatment for PNH patients to control hemolytic attack, and the short-term remission rate (12 months) is 79.01% (64/81). Meanwhile, the overall survival (OS) of 10 years after diagnosis was estimated as 70.77% (46/65). Moreover, Cox proportional risk model for multivariate analysis showed that the increase in LDH multiple, thrombosis complications, and complicated with bone marrow failure were the independent adverse prognostic factors affecting the survival of PNH patients. CONCLUSION: Paroxysmal nocturnal hemoglobinuria patients in mainland China have various clinical features, while lower incidences of thrombosis and renal damage. Thrombosis and bone marrow failure are two complications with worse prognosis.
Assuntos
Hemoglobinúria Paroxística/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Hemoglobinúria Paroxística/fisiopatologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Despite the milder clinical severity of Hb H patients compared with those of Hb Bart's hydrops fetalis or patients with ß-thalassemia major (ß-TM), a few cases of Hb H hydrops fetalis syndrome have been reported so far. Here, we describe, for the first time in the Chinese population, one case of a neonate with Hb H hydrops fetalis syndrome caused by the - -SEA (Southeast Asian) deletion in combination with the Hb Hirosaki (HBA2: c.132C>G, p.Phe43Leu) mutation. Our study highlights the importance of continuous fetal monitoring using ultrasonography and blood screening studies of fetuses. Appropriate genetic counseling and comprehensive clinical follow-up should be performed on a pregnant woman who carried an α0-thalassemia (α0-thal) deletion and had a Hb H or Hb Bart's hydrops fetalis offspring, especially if the woman's partner also carried a hemoglobinopathy.