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During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance in vivo. Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 in vivo.
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BACKGROUND: Autologous fat is a rich source of adipose tissue that is safe for transplantation. Decreasing the long-term absorption rate is key to improve the survival of transplanted adipose tissue. The aim of this study was to assess the effect of concentrated growth factor (CGF) on the survival of transplanted adipose tissue for repair of facial depression malformations. METHODS: Coleman adipose granules (CAGs) were prepared from venous blood. In the animal experiment, the ears of 30 healthy male New Zealand white rabbits were randomly allocated to 1 of 4 groups: CGF + CAG (CGF group), platelet-rich fibrin (PRF) + CAG (PRF group), CAG alone (CAG group), and adipose granule transplantation group (control group). Postoperative survival of the transplanted adipose tissue was assessed, the survival and absorption rates of adipose were calculated, and immunohistochemical analysis of specimens was conducted by staining with hematoxylin and eosin and Oil Red O. Of 43 outpatients, 22 received simple adipose transplantation and 21 received autologous CGF combined with adipose transplantation. The adipose absorption rate, complication rate, and cosmetic improvement of the 2 groups were compared. RESULTS: More adipocytes that are normal were observed in the CGF group, with fewer vacuoles and more uniform distribution of adipose tissue. Survival of the adipose tissue was superior in the CGF and PRF groups. Meanwhile, vascular density and long-term stability were better in the CGF group than the PRF group. In terms of clinical efficacy, the uniformity and survival rate of the adipose tissue were relatively improved in the CGF group compared with the simple adipose particle transplantation group, with less early liquefaction. CONCLUSION: Concentrated growth factor stabilized and improved the survival of transplanted adipose tissue for filling of facial depression malformations.
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Obesidade Mórbida , Obesidade , Masculino , Animais , Coelhos , Tecido Adiposo , Peptídeos e Proteínas de Sinalização Intercelular , AdipócitosRESUMO
The nucleus accumbens (NAc) is the most promising target for drug use disorder treatment. Deep brain stimulation (DBS) of NAc is effective for drug use disorder treatment. However, the mechanisms by which DBS produces its therapeutic effects remain enigmatic. Here, we define a behavioral cutoff criterion to distinguish depressive-like behaviors and non-depressive-like behaviors in mice after morphine withdrawal. We identified a basolateral amygdala (BLA) to NAc D1 medium spiny neuron (MSN) pathway that controls depressive-like behaviors after morphine withdrawal. Furthermore, the paraventricular nucleus of thalamus (PVT) to NAc D2 MSN pathway controls naloxone-induced acute withdrawal symptoms. Optogenetically induced long-term potentiation with κ-opioid receptor (KOR) antagonism enhanced BLA to NAc D1 MSN signaling and also altered the excitation/inhibition balance of NAc D2 MSN signaling. We also verified that a new 50 Hz DBS protocol reversed morphine withdrawal-evoked abnormal plasticity in NAc. Importantly, this refined DBS treatment effectively alleviated naloxone-induced withdrawal symptoms and depressive-like behaviors and prevented stress-induced reinstatement. Taken together, the results demonstrated that input- and cell type-specific synaptic plasticity underlies morphine withdrawal, which may lead to novel targets for the treatment of opioid use disorder.
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Analgésicos Opioides , Síndrome de Abstinência a Substâncias , Camundongos , Animais , Analgésicos Opioides/farmacologia , Núcleo Accumbens/metabolismo , Receptores de Dopamina D2 , Morfina/efeitos adversos , Naloxona/farmacologia , Naloxona/metabolismo , Síndrome de Abstinência a Substâncias/terapia , Receptores de Dopamina D1/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Isoprenoids, a large kind of plant natural products, are synthesized by the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids. As one of the rate-limiting enzymes in the MVA pathway of soybean (Glycine max), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is encoded by eight isogenes (GmHMGR1-GmHMGR8). To begin, we used lovastatin (LOV), a specific inhibitor of GmHMGR, to investigate their role in soybean development. To further investigate, we overexpressed the GmHMGR4 and GmHMGR6 genes in Arabidopsis thaliana. The growth of soybean seedlings, especially the development of lateral roots, was inhibited after LOV treatment, accompanied by a decrease in sterols content and GmHMGR gene expression. After the overexpression of GmHMGR4 and GmHMGR6 in A. thaliana, the primary root length was higher than the wild type, and total sterol and squalene contents were significantly increased. In addition, we detected a significant increase in the product tocopherol from the MEP pathway. These results further support the fact that GmHMGR1-GmHMGR8 play a key role in soybean development and isoprenoid biosynthesis.
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Arabidopsis , Glycine max , Glycine max/genética , Glycine max/metabolismo , Terpenos/metabolismo , Esqualeno/metabolismo , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Lovastatina/farmacologia , Coenzima A/metabolismo , Ácido Mevalônico/metabolismoRESUMO
Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.
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Arsênio , Arsenicais , Leucemia Promielocítica Aguda , Humanos , Adulto , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Trióxido de Arsênio/efeitos adversos , Arsênio/uso terapêutico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Óxidos/uso terapêutico , Arsenicais/efeitos adversosRESUMO
Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment. Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks. Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups. Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02908958.
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Objective: To investigate and analyse the situation and relationship between adolescent physical activity and self-assessment of health to provide a reference for adolescent physical activity research. Methods: A questionnaire was used to investigate the physical activity and self-rated health of 1,804 adolescents aged 14-18 years. Results: There was a significant relationship between adolescents' physical activity and self-rated health. The coefficient was 0.109 (P < 0.01) in urban areas and 0.127 (P < 0.01) in rural areas. At the same time, it was found that when family income was used as the intermediary variable between physical activity and self-rated health, the intermediary effect was 0.12 (P < 0.01), and the intermediary effect accounted for 25.97%. Conclusion: Adolescent obesity, physical activity, smoking, wellbeing and physical activity can affect adolescents' self-rated health status. At the same time, it is also found that adolescents' family income is an intermediary variable between physical activity and self-rated health. Suggestions: (1) Increase the methods of sports venues, sports organizations and sports activities, improve the possibility of teenagers participating in physical activities, and improve teenagers' self-rated health; (2) There is a large gap between the physical activity and self-rated health of urban and rural adolescents. Increasing the guidance of physical activity of adolescents in rural areas promotes the balance of self-rated health of urban and rural adolescents. (3) Family income is the intermediary variable of teenagers' physical activities and self-rated health. Reducing family expenditure through financial transfer payments or reducing taxes and fees can increase the level of teenagers' physical and mental health.
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Obesidade Infantil , Adolescente , Exercício Físico , Nível de Saúde , Humanos , Renda , Saúde MentalRESUMO
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Transcriptoma , Criança , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genéticaRESUMO
Refractory wounds present a complex and serious clinical dilemma in plastic and reconstructive surgery. However, there are currently no standard guidelines for the treatment of refractory wounds. Artificial dermis (AD) has achieved some satisfactory results, but also has some limitations. Autologous platelet-rich plasma (PRP), as a cell-therapy material, was a valuable and safe treatment dressing for chronic non-healing wounds. This study aimed to evaluate the efficacies of artificial dermis (AD) with and without autologous platelet-rich plasma (PRP) in patients with refractory wounds. Sixteen patients with refractory wounds were randomly allocated to autologous PRP therapy combined with artificial dermis (PRP + AD [N = 8]) or an artificial dermis program only (AD [N = 8]). We compared the efficacies of the two methods in terms of times to wound healing, infection control, and AD vascularization, as well as hospitalization days and eventual clinical outcomes.13 patients achieved complete healing, including seven (87.5%) in the PRP + AD group and six (75.0%) in the AD group (P > .05). The times to wound healing, infection control, and AD vascularization, and hospitalization time after transfer were significantly shorter in the PRP + AD group compared with the AD group (P < .05). In conclusion, the combination of AD and PRP promoted refractory wound healing and shortened waiting times compared with simple dermal grafts.
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As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Trióxido de Arsênio/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Quimioterapia de Consolidação/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Tretinoína/efeitos adversosRESUMO
Melanoma is an extremely malignant and occult tumor. To identify candidate genes related to melanoma carcinogenesis and progression, the microarray data sets GSE83583, GSE130244, and GSE31879 were retrieved from the Gene Expression Omnibus (GEO) database using the GEO2R analytical tool provided by the National Center for Biotechnology Information (NCBI). Gene expression analysis was carried out using the DAVID database for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses of differentially expressed genes. A protein-protein interaction network was constructed with the STRING database, the interaction data were imported into Cytoscape software, and the network topology was analyzed to identify key genes. Hub gene expression was verified in the Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases. In addition, Kaplan-Meier survival analysis was performed on hub genes. A total of 142 differentially expressed genes were identified in melanoma tissues, including 50 upregulated genes and 92 downregulated genes. Five central genes (CCNA2, EBP, GABBR2, TRIM32, and ADAM10) were found based on the degree of the nodes. These genes are mainly enriched in protein serine/threonine kinase activity and apoptosis pathways. Survival analysis showed CCNA2 to be related to the overall survival (OS) of patients, and increased expression of TRIM32 led to increased OS and disease-free survival risk. Bioinformatics methods can be used to effectively select key genes in melanoma, and CCNA2 and TRIM32 may be new targets for treatment of this disease.
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Biomarcadores Tumorais/genética , Melanoma/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Regulação para Baixo/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Genoma Humano/genética , Humanos , Prognóstico , Mapas de Interação de Proteínas/genética , Regulação para Cima/genéticaRESUMO
The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.
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Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Terapia Combinada , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Transplante de Células-Tronco Hematopoéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China. Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed. Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16-82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5-70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS. Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.
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Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and ß cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).
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Antineoplásicos/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adulto JovemRESUMO
China harbors 56 ethnic groups and Han is the largest population. It is informative and useful to explore the available population genetic characteristics of Chinese Han population from Fujian Province, Southeast China. In our study, we explored the genetic characteristics of 20 autosomal Short tandem repeat (STR) loci in 1555 unrelated Chinese Han individuals from Zhangzhou City, Southeastern China using the SureID® 21G Human STR Identification Kit. Moreover, phylogenetic analysis was performed between the Zhangzhou Han population and other relevant populations based on the shared autosomal STR genotyping. The neighbor-joining tree and multidimensional scaling analysis were analyzed based on the Nei's standard genetic distance. We found 262 alleles among 1555 unrelated individuals and the corresponding allele frequencies ranged from 0.5521 to 0.0003. The combined power of discrimination and exclusion of the 20 autosomal STR loci were 0.99999999999999999999999943 and 0.999999996166537, respectively. Population comparison revealed that the Zhangzhou Han population were lining up together with the southern Han populations in China while showed significant differences from other China populations. Our results found that the 20 autosomal STR loci in Zhangzhou Han population are meaningful for forensic medicine and human genetic. The genetics characteristic of Zhangzhou Han population is similar with the southern Han population in China.
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Povo Asiático/genética , Medicina Legal , Loci Gênicos/genética , Genética Populacional/métodos , Repetições de Microssatélites/genética , China , Humanos , Polimorfismo GenéticoRESUMO
Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Aclarubicina/farmacologia , Aclarubicina/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Estudos de Coortes , Citarabina/farmacologia , Citarabina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
Leucemia Promielocítica Aguda , Complexo de Proteínas Formadoras de Poros Nucleares , Proteínas de Fusão Oncogênica , RNA Mensageiro , RNA Neoplásico , Receptor alfa de Ácido Retinoico , Adulto , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Masculino , Complexo de Proteínas Formadoras de Poros Nucleares/biossíntese , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Receptor alfa de Ácido Retinoico/biossíntese , Receptor alfa de Ácido Retinoico/genéticaRESUMO
Infant hemangioma is the most common benign tumor in infancy. The pathological development process of this tumor is separated into the proliferation period, the involution period and the composite period in which a few residual capillarylike vessels grow through the loose fibrofatty tissue. Previous studies have confirmed that insulinlike growth factor 1 (IGF1) is able to facilitate the cell proliferation of hemangioma stem cells (HemSCs) and the differentiation of HemSCs into adipocytes. Additionally, studies have confirmed that microRNAs (miRs) may serve a crucial function in regulating the IGF1 receptor (IGF1R). miR1395p often functions as a tumor suppressor. The present study was designed to investigate the mechanism of miR1395p in HemSCs. Dual luciferase reporter results verified that IGF1R is the target gene of miR1395p. miR1395p overexpression reduced IGF1R expression, and miR1395p inhibition increased IGF1R expression. Cell Counting Kit8 and Transwell migration assays demonstrated that miR1395p overexpression may target IGF1R to inhibit the proliferation in addition to the migration of HemSCs. Reverse transcriptionquantitative PCR, oil red o staining and western blot analysis confirmed that miR1395p overexpression was able to reduce adipogenesis in HemSCs via the IGF1/IGF1R pathway. In contrary, miR1395p inhibition substantially enhanced the proliferation, migration and adipogenesis of HemSCs. Overall, miR1395p is able to affect the IGF1/IGF1R pathway by regulating IGF1R expression, which ultimately affects the proliferation, migration and adipogenesis of HemSCs.
Assuntos
Adipogenia , Hemangioma/genética , MicroRNAs/genética , Receptor IGF Tipo 1/genética , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Hemangioma/patologia , Humanos , Lactente , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
BACKGROUND: It is meaningful to expand the available population information on forensic medicine and to investigate the genetic characteristics of Han population from Jilin Province, Northeast China. METHODS: In this study, we investigated the genetic characteristics of 24 Y-chromosomal short tandem repeat (STR) loci in 1,088 unrelated Chinese Han male individuals from Jilin Province, using DNATyperTM Y24 amplification kit. Additionally, we performed the population comparison between the Jilin population and the other nine reported populations based on the Y-STR genotyping haplotypes. RESULTS: A total of 1,067 different haplotypes were found from 1,088 unrelated individuals, of which 1,046 were unique and 21 were shared by two individuals. The gene diversity values of 22 loci ranged from 0.3870 (DYS391) to 0.9668 (DYS385ab). The random match probability was 0.0010 with the discrimination capacity of 0.9807. Population comparison showed that there were minor differences compared to Beijing Chinese Han, China Manchu, Gansu Chinese Han, and Jiangsu Chinese Han, but major differences with respect to the populations of Guangdong Chinese Han, Yunnan Chinese Han, China Hui, China Korean, and China Tibetan. CONCLUSION: Our results showed that the 24 Y-STR loci in Jilin Han population are valuable for forensic application and human genetics.