RESUMO
Soil salinity poses a serious threat to rice production. The salt tolerance of rice at the germination stage is one of the major determinants of stable stand establishment, which is very important for direct seeding in saline soil. The complexity and polygenic nature of salt tolerance have limited the efficiency of discovering and cloning key genes in rice. In this study, an RIL population with an ultra-high-density genetic map was employed to investigate the salt-tolerant genetic basis in rice, and a total of 20 QTLs were detected, including a major and stable QTL (qRCL3-1). Subsequently, salt-specific DEGs from a comparative transcriptome analysis were overlaid onto annotated genes located on a stable QTL interval, and eight putative candidate genes were further identified. Finally, from the sequence alignment and variant analysis, OsCam1-1 was confirmed to be the most promising candidate gene for regulating salinity tolerance in rice. This study provides important information for elucidating the genetic and molecular basis of rice salt tolerance at the germination stage, and the genes detected here will be useful for improvements in rice salt tolerance.
Assuntos
Mapeamento Cromossômico , Perfilação da Expressão Gênica , Germinação , Oryza , Locos de Características Quantitativas , Tolerância ao Sal , Oryza/genética , Oryza/crescimento & desenvolvimento , Tolerância ao Sal/genética , Germinação/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Transcriptoma/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Weedy rice (Oryza sativa f. spontanea) is a relative of cultivated rice that propagates in paddy fields and has strong drought resistance. In this study, we used 501 rice accessions to reveal the selection mechanism of drought resistance in weedy rice through a combination of selection analysis, genome-wide association studies, gene knockout and overexpression analysis, and Ca2+ and K+ ion flux assays. The results showed that the weedy rice species investigated have gene introgression with cultivated rice, which is consistent with the hypothesis that weedy rice originated from de-domestication of cultivated rice. Regions related to tolerance have particularly diversified during de-domestication and three drought-tolerance genes were identified. Of these, Os01g0800500 was also identified using an assay of the degree of leaf withering under drought, and it was named as PAPH1, encoding a PAP family protein. The drought-resistance capacity of PAPH1-knockout lines was much lower than that of the wild type, while that of overexpression lines was much higher. Concentrations of Ca2+ and K+ were lower in the knockout lines and higher in the overexpression lines compared with those of the wild type, suggesting that PAPH1 plays important roles in coping with drought stress. Our study therefore provides new insights into the genetic mechanisms underlying adaptive tolerance to drought in wild rice and highlights potential new resistance genes for future breeding programs in cultivated rice.
Assuntos
Oryza , Secas , Evolução Molecular , Estudo de Associação Genômica Ampla , Oryza/genética , Melhoramento Vegetal , Plantas DaninhasRESUMO
To isolate the genetic locus responsible for saline-alkaline stress tolerance, we developed a high-throughput activation tagging-based T-DNA insertion mutagenesis method using the model rice (Oryza sativa L.) variety Kitaake. One of the activation-tagged insertion lines, activation tagging 7 (AC7), showed increased tolerance to saline-alkaline stress. This phenotype resulted from the overexpression of a gene that encodes a SET DOMAIN GROUP 721 protein with H3K4 methyltransferase activity. Transgenic plants overexpressing OsSDG721 showed saline-alkaline stress-tolerant phenotypes, along with increased leaf angle, advanced heading and ripening dates. By contrast, ossdg721 loss-of-function mutants showed increased sensitivity to saline-alkaline stress characterized by decreased survival rates and reduction in plant height, grain size, grain weight and leaf angle. RNA sequencing (RNA-seq) analysis of wild-type Kitaake and ossdg721 mutants indicated that OsSDG721 positively regulates the expression level of HIGH-AFFINITY POTASSIUM (K+ ) TRANSPORTER1;5 (OsHKT1;5), which encodes a Na+ -selective transporter that maintains K+ /Na+ homeostasis under salt stress. Furthermore, we showed that OsSDG721 binds to and deposits the H3K4me3 mark in the promoter and coding region of OsHKT1;5, thereby upregulating OsHKT1;5 expression under saline-alkaline stress. Overall, by generating Kitaake activation-tagging pools, we established that the H3K4 methyltransferase OsSDG721 enhances saline-alkaline stress tolerance in rice.
Assuntos
Oryza , Regulação da Expressão Gênica de Plantas/genética , Oryza/metabolismo , Domínios PR-SET , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Sódio/metabolismo , Estresse Fisiológico/genéticaRESUMO
INTRODUCTION: Tigecycline (TGC) is effective for the infections caused by carbapenem-resistant gram-negative bacteria (CRGNB) in adults, but it is not investigated systematically in children because of concern about adverse effects. This study aimed to analyze the effectiveness of TGC in treating CRGNB infections in children after receiving liver transplant. METHODS: The subjects in this retrospective study were pediatric liver transplant recipients treated with TGC for at least 3 days to fight microbiologically verified CRGNB infection after initial antibiotic failure during the period from January 2014 to May 2018. Clinical and microbiological outcomes were reviewed to evaluate the efficacy and safety of TGC. RESULTS: Of the 1177 pediatric liver transplant recipients, 13 patients were eligible for inclusion in this analysis. All the patients received TGC at dose of 2 mg/kg every 12 hours for a duration of 10.1 ± 5.1 days on average to treat CRGNB infections, including complicated intra-abdominal infection, ventilator-associated pneumonia, and bloodstream infection. The isolates included Klebsiella pneumoniae (69.2%, 9/13) and Acinetobacter baumannii (30.8%, 4/13). Clinical efficacy was achieved in 84.6% (11/13) and pathogen eradicated in 69.2% (9/13) of the patients. The overall mortality rate was 15.4% (2/13). No TGC-related serious adverse event was reported. CONCLUSION: Tigecycline can be considered in combination antimicrobial regimen for treating CRGNB-related infections in pediatric liver transplant recipients.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Transplante de Fígado , Tigeciclina/uso terapêutico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Pré-Escolar , Feminino , Humanos , Lactente , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We evaluated the effects of liver transplantation (LT) in children with Niemann-Pick disease (NPD) type B. From October 2006 to October 2018, 7 of 1512 children who received LT at Ren Ji Hospital were diagnosed as NPD type B. The median age at diagnosis was 12 months (6-14 months) with initial presentations of hepatosplenomegaly, growth retardation, repeated pneumonia, and diarrhea. Even after comprehensive supporting treatments, all patients developed liver dysfunction, severe interstitial pulmonary disease, compromised lung function, and hypersplenism, with hypertriglyceridemia in 4 patients. They were transferred to our hospital for transplantation (median age, 6.5 years; range, 2.2-8.6 years). Among them, 4 patients received living donor LT, and 3 received whole-liver orthotopic LT. Splenectomy was conducted spontaneously. All patients are alive with a median follow-up of 10 months (range, 5-53 months). Liver function normalized within 3 weeks after transplantation and maintained stability. Thrombocytopenia and leukopenia were cured, as was hypertriglyceridemia. Strikingly, pulmonary disease was relieved after transplantation, as evidenced by resolution of interstitial lung disease and restored lung function. Bronchitis occurred only once among the 3 patients with a quick recovery during follow-up. Catch-up growth was observed in all patients, especially in 1 male patient, as his height z score increased from -3.9 to -1 at 4 years after transplantation. Patients with follow-up longer than 10 months indicated significant psychomotor ability improvement. Hypotonia was relieved in 4 patients after transplantation. However, intelligence developmental delay still existed in 4 patients during the follow-up. Three of them have been receiving intelligence recovery therapy, although the longterm effect needs more investigation. In conclusion, LT is a safe and effective treatment for patients with NPD type B with severe liver and pulmonary dysfunction.
Assuntos
Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/prevenção & controle , Transplante de Fígado/estatística & dados numéricos , Doença de Niemann-Pick Tipo B/cirurgia , Desempenho Psicomotor/fisiologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Seguimentos , Humanos , Transplante de Fígado/métodos , Masculino , Doença de Niemann-Pick Tipo B/sangue , Doença de Niemann-Pick Tipo B/complicações , Doença de Niemann-Pick Tipo B/fisiopatologia , Resultado do TratamentoRESUMO
KEY MESSAGE: FLA, the homolog of ubiquitin-specific protease does not have deubiquitination activity, but it is essential for flower and chloroplast development in rice. Ubiquitin-specific proteases (UBPs) are widely distributed and highly conserved proteins and are also members of the most important family of deubiquitination enzymes. Although the functions and phylogenies of UBPs from yeast, mammals and Arabidopsis have been widely reported, the functions and evolutionary relationships of UBPs in rice remain unclear. In this study, we characterized the rice flower and leaf color aberrant mutant (fla), which exhibited a variety of developmental defects, including abnormal floral organs and pollen development, and leaf bleaching. We isolated FLA by positional cloning and found that it encodes a homolog of ubiquitin-specific protease. FLA is a ubiquitously expressed gene with the highest expression in floral organs. Subcellular localization analysis indicated that FLA is a cell membrane protein. Through searches of the rice genome database ( http://rice.plantbiology.msu.edu ), we identified 35 UBP family members in the rice genome. These proteins were grouped into 16 subfamilies based on phylogenetic analysis, and FLA was found to belong to the G8 subfamily. In vitro activity assays revealed that FLA does not have deubiquitination activity. Our data suggest that FLA plays an important role in the development of floral organs and chloroplast in rice, but that this role probably does not involve deubiquitination activity, because FLA does not have an active site and deubiquitination activity.
Assuntos
Clorofila/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Genoma de Planta/genética , Filogenia , Proteínas de Plantas/genéticaRESUMO
BACKGROUND: Previous nomograms for intrahepatic cholangiocarcinoma (ICC) were conducted to predict overall survival, which could be influenced by various factors. Herein, we conducted our nomogram to predict recurrence of the tumor only after hepatic resection. METHODS: The nomogram was established with prognostic factors for the relapse-free survival (RFS) analyzed from our single center cohort and was evaluated by comparing with the American Joint Committee on Cancer (AJCC) staging system for the predictive accuracy. RESULTS: Seropositivity of hepatitis B surface antigen (hazard ratio [HR], 0.505; 95% confidence interval [CI], 0.279 to 0.914; P = 0.024), tumor size of larger than 5 cm (HR, 1.947; 95% CI, 1.177 to 3.219; P = 0.009), Child-Pugh score of B (HR, 3.067; 95% CI, 1.293 to 7.275; P = 0.011), and lymph node metastasis (HR, 2.790; 95% CI, 1.628 to 4.781; P < 0.001) were found to be independent prognostic factors that significantly affected RFS. The calibration curve for the prediction revealed excellent agreement between estimation by our stratification system and actual RFS. The concordance C index of the nomogram (0.71; 95% CI, 0.65 to 0.77) revealed to be significantly higher than the AJCC staging system (0.66; 95% CI, 0.60 to 0.72). In the validation cohort, our risk stratification system (C-index 0.65; 95% CI, 0.59 to 0.71) also revealed more precise prediction than the AJCC staging system (C-index, 0.57; 95% CI, 0.50 to 0.64). CONCLUSIONS: Our nomogram could more accurately predict recurrence of ICC after hepatic resection than the AJCC staging system.
Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Carga TumoralRESUMO
BACKGROUND: Early hepatic artery thrombosis (eHAT) has been recognized as an important cause of graft loss and mortality. However, the incidence, etiology and outcome are not clear, especially for children. The present study was to investigate the formation of collateral artery flow after irreversible eHAT and its impact on patient's prognosis. METHODS: We analyzed eHAT after liver transplantation in children from October 2006 to April 2015 in our center, illustrated the formation of collateral hepatic artery flow after irreversible eHAT and explored the diagnosis, complications, treatment and prognosis. The basic and follow-up ultrasonographic images were also compared. RESULTS: Of the 330 pediatric liver recipients, 22 (6.67%) developed eHAT within 1 month. Revascularization attempts including surgical thrombectomy, interventional radiology and conservational treatment (thrombolysis) were successful in 5 patients. Among the 17 patients who had irreversible eHAT, follow-up ultrasonography revealed that collateral artery flow was developed as early as 2 weeks after eHAT. Liver abscess and bile duct complication occurred secondary to eHAT in variable time. CONCLUSIONS: Collateral arterial formation is a compensatory adaptation to eHAT to supply blood to liver grafts. However, the severe bile duct damage secondary to eHAT is irreversible and retransplantation is unavoidable.
Assuntos
Arteriopatias Oclusivas/etiologia , Circulação Colateral , Artéria Hepática/fisiopatologia , Circulação Hepática , Transplante de Fígado/efeitos adversos , Trombose/etiologia , Fatores Etários , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/terapia , Doenças dos Ductos Biliares/etiologia , Doenças dos Ductos Biliares/fisiopatologia , Criança , Pré-Escolar , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Lactente , Masculino , Reoperação , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/fisiopatologia , Trombose/terapia , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia DopplerRESUMO
Leaf rolling is an important agronomic trait in crop breeding. Moderate leaf rolling maintains the erectness of leaves and minimizes shadowing between leaves, leading to improved photosynthetic efficiency. Although some genes controlling leaf rolling have been isolated from rice and other plant species, few studies have examined leaf rolling in wheat. In the present study, the leaf rolling regulator gene, TaMYB18, was identified in a large-scale transgene project involving the transformation of 1455 wheat transcription factor genes into rice. Three homologous sequences of TaMYB18 were isolated from hexaploid wheat and localized to chromosomes 5A, 5B and 5D, respectively. TaMYB18, an R2R3-MYB transcription factor, localized to the nucleus. TaMYB18 overexpression induced leaf rolling in transgenic rice. Additionally, the three members of TaMYB18 exhibited functional redundancy in rice. Furthermore, the function of TaMYB18 in regulating leaf rolling in rice was a dose-dependent. Taken together, these results indicate that TaMYB18 may play an important role in the regulation of leaf development.
Assuntos
Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Oryza/fisiologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Ativação Transcricional/fisiologia , Proteínas de Plantas/genéticaRESUMO
KEY MESSAGE: Diachronic analysis showed no significant changes in the level of genetic diversity occurred over the past 27 years' domestication, which indicated genetic diversity was successfully maintained under on-farm conservation. Rice (Oryza sativa L.) is one of the earliest domesticated crop species. Its genetic diversity has been declining as a result of natural and artificial selection. In this study, we performed the first analysis of the levels and patterns of nucleotide variation in rice genomes under on-farm conservation in Yunnan during a 27-year period of domestication. We performed large-scale sequencing of 600 rice accessions with high diversity, which were collected in 1980 and 2007, using ten unlinked nuclear loci. Diachronic analysis showed no significant changes in the level of genetic diversity occurring over the past 27 years' domestication, which indicated genetic diversity was successfully maintained under on-farm conservation. Population structure revealed that the rice landraces could be grouped into two subpopulations, namely the indica and japonica groups. Interestingly, the alternate distribution of indica and japonica rice landraces could be found in each ecological zone. The results of AMOVA showed that on-farm conservation provides opportunities for continued differentiation and variation of landraces. Therefore, dynamic conservation measures such as on-farm conservation (which is a backup, complementary strategy to ex situ conservation) should be encouraged and enhanced, especially in crop genetic diversity centers. The results of this study offered accurate insights into short-term evolutionary processes and provided a scientific basis for on-farm management practices.
Assuntos
Conservação dos Recursos Naturais , Variação Genética , Genoma de Planta , Oryza/genética , China , Produtos Agrícolas/genética , DNA de Plantas/genética , Genética Populacional , Genótipo , Haplótipos , Repetições de Microssatélites , Modelos Genéticos , Filogenia , Análise de Sequência de DNARESUMO
We investigated the overall situation of LT for BA in mainland China and analyzed their survival outcomes based on data from CLTR. Between January 1996 and December 2013, 509 liver transplants for BA were performed in mainland China and were included in this study. Patients' median age was 9.6 months (range: 4.8-175.2 months). KP was previously performed in 194 cases (38.1%). Grafts from living donors were used in 380 cases (74.7%). Era I (1996.1-2010.12) and era II (2011.1-2013.12) comprised 151 cases (29.7%) and 358 cases (70.3%), respectively. Twenty-five centers had performed at least one liver transplant for children with BA. Centers from Shanghai (197 cases), Tianjin (143 cases) and Beijing (81 cases) involved 82.7% of the 509 cases. One- and five-yr graft survival rates were 84.7% and 72.6%, respectively. Split grafts, center volume <20, GRWR ≥4.0%, and steroid-free immunosuppression regimen were independent risk factors for graft survival. In conclusion, the dramatic expansion of pediatric liver transplant programs in mainland China has enabled improved survival for those children affected by this devastating disease. However, screening of BA in neonates should be emphasized throughout the country to enhance early referrals for KP.
Assuntos
Atresia Biliar/cirurgia , Transplante de Fígado , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Lactente , Falência Hepática/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Through large-scale transformation analyses, TaMYB72 was identified as a flowering time regulator in wheat. TaMYB72 is a MYB family transcription factor localized to the nucleus. Three TaMYB72 homologs, TaMYB72-A, TaMYB72-B and TaMYB72-D, cloned from hexaploid wheat were mapped to the short arm of the group 6 chromosomes. Under the long-day conditions, over-expression of the TaMYB72 in rice shortened the flowering time by approximately 12 d. Expression analyses suggest that TaMYB72 may function through up-regulation of florigen genes Hd3a and RFT1.
Assuntos
Flores/fisiologia , Oryza/genética , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Triticum/metabolismo , Regulação da Expressão Gênica de Plantas , Fotoperíodo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Fatores de Transcrição/genéticaRESUMO
We used Doppler US to evaluate the changes in hepatic arterial hemodynamics that occur following LDLT in pediatric recipients, with a view to assessing the utility of these parameters in predicting early HAT. A retrospective review of 144 pediatric recipients (73 males, 71 females) who underwent routine Doppler US in the first week after LDLT was undertaken, and changes in hepatic arterial hemodynamics were assessed. The HARI and HAPSV were compared in patients with early HAT (defined as occurring in the first postoperative week) and a control group, and the utility of these parameters in predicting early HAT after LDLT was determined. A total of 11 pediatric recipients experienced early HAT, being diagnosed on average four and a half days after LDLT. HARI and HAPSV values were significantly different between the early HAT group and controls. HARI values <0.6 on the day before the onset of early HAT were able to predict HAT development with a sensitivity of 81.8% and specificity of 95.2%. This provides evidence for routine Doppler US examination in these patients and supports consideration of more intensive anticoagulation in these high-risk patients.
Assuntos
Artéria Hepática/patologia , Falência Hepática/cirurgia , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Trombose/diagnóstico , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Hemodinâmica , Humanos , Lactente , Fígado/diagnóstico por imagem , Doadores Vivos , Masculino , Curva ROC , Estudos Retrospectivos , Risco , Sensibilidade e Especificidade , Trombose/patologia , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia DopplerRESUMO
LDLT is a well-established treatment for most terminal liver diseases in children. Survival rates have improved, yet few studies have considered HRQoL or sleep problems in LDLT recipients. In this cross-sectional study, we enrolled 51 children who had undergone LDLT in Renji Hospital. PedsQL(™) 4.0 Generic Core Scales, PedsQL(™) 3.0 Transplant Module, and Pediatric Sleep Questionnaire were used to assess outcomes. Of all participants, 11.8% (6/51) reported low total HRQoL scores. Participants' scores on most HRQoL subscales were comparable to the scores of healthy children. However, compared with solid organ transplant recipients, LDLT recipients scored significantly lower in About My Medicines II (t = 3.092, p = 0.002) and Worry (t = 2.760, p = 0.006). Sleep problems (41.2%) were common among participants. Hierarchical regression analyses showed that SRBD accounted for significant variance in HRQoL on total generic HRQoL (R(2) = 0.446, p < 0.001), psychosocial health (R(2) = 0.372, p = 0.001), physical health (R(2) = 0.345, p = 0.003), total transplant-specific HRQoL (R(2) = 0.514, p < 0.001), About My Medicines I (R(2) = 0.365, p = 0.013), My Transplant and Others (R(2) = 0.334, p = 0.005), Pain and Hurt (R(2) = 0.544, p < 0.001), Worry (R(2) = 0.401, p = 0.001), Treatment Anxiety (R(2) = 0.526, p < 0.001), How I Look (R(2) = 0.221, p = 0.040), and Communication (R(2) = 0.343, p = 0.012). In conclusion, sleep problems are non-negligible in children after LDLT and predicted significant variance on HRQoL.
Assuntos
Falência Hepática/psicologia , Falência Hepática/cirurgia , Transplante de Fígado/psicologia , Doadores Vivos , Qualidade de Vida , Sono , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Transplante de Fígado/métodos , Masculino , Psicometria , Transtornos do Sono-Vigília/complicações , Inquéritos e Questionários , Resultado do TratamentoRESUMO
We aimed to assess the impact of size mismatching between grafts and recipients on outcomes of infants or small children after LDLT. Between October 2006 and December 2014, 129 LDLT recipients weighing no more than 8 kg were retrospectively analyzed. The entire cohort was categorized into three groups by GRWR: GRWR < 3.0% (group A, n = 38), 3.0% ≤ GRWR < 4.0% (group B, n = 61), and GRWR ≥ 4.0% (group C, n = 30). Baseline characteristics were similar among groups A, B, and C. Compared with groups A and B, post-transplant alanine aminotransferase and aspartate aminotransferase within seven days were significantly higher in group C; however, differences between total bilirubin and albumin after transplantation were not prominent. Moreover, incidences of surgical complications, perioperative deaths, infections, and acute rejections were all comparable among the three groups. Five-yr patient survival rates for groups A, B, and C were 89.5%, 88.9%, and 81.6%, respectively (p = 0.872), and the graft survival rates were 89.5%, 86.6%, and 81.6%, respectively (p = 0.846). In conclusion, GRWR between 1.9% and 5.8% would not cause noticeable adverse events for infantile LDLT recipients ≤ 8 kg. However, there is still a role for considering reduction in the graft mass as an applicable strategy in selected cases.
Assuntos
Peso Corporal , Transplante de Fígado/métodos , Fígado/anatomia & histologia , Doadores Vivos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Masculino , Tamanho do Órgão , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND AIMS: Neurensin-2 (NRSN2) is a neuronal membrane protein; previous reports indicated that it might function as a tumor suppressor in hepatocellular carcinoma (HCC). However, its biological functions and associated mechanisms remain unknown. In the current study, we aimed to investigate the biological functions and possible mechanisms of neurensin-2. METHODS: The mRNA and protein level of NRSN2 in HCC has tissues and cell lines were detected by quantitative real-time PCR, immunohistochemistry staning and western blot. Overexpressing and silencing the level of NRSN2 in HCC cell lines were used to investigate the role of NRSN2 in HCC. CCK-8 assays, SA-ß gel staining, Annexin V/PI staining, quantitative real-time PCR and western blot were employed to explore the role and mechanisms of HCC. RESULTS: NRSN2 was more commonly down-regulated HCC tissues compared with adjacent tissues, and the expression pattern of NRSN2 was not only closely correlated with tumor size and TNM stage but also negatively correlated with patient prognosis. Both loss and gain function assays revealed that NRSN2 inhibits cancer cell proliferation and promotes cancer cell senescence and apoptosis. We further found that NRSN2 might regulate PI3K/AKT signaling and p53/p21 pathway to exert its role in HCC cell proliferation, senescence and apoptosis. CONCLUSION: Our study validates the suppressive role of NRSN2 in both clinicopathologic and biological aspects in HCC tumorigenesis.
Assuntos
Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Adolescente , Adulto , Idoso , Biópsia por Agulha , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Senescência Celular/genética , Distribuição de Qui-Quadrado , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos de Amostragem , Sensibilidade e Especificidade , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas , Adulto JovemRESUMO
BACKGROUND: Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT. METHODS: One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. RESULTS: Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT. CONCLUSIONS: Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.
Assuntos
Atresia Biliar/cirurgia , Hemodinâmica , Transplante de Fígado/efeitos adversos , Veia Porta/cirurgia , Cuidados Pré-Operatórios/métodos , Trombose Venosa/etiologia , Área Sob a Curva , Atresia Biliar/diagnóstico por imagem , Atresia Biliar/fisiopatologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler em CoresRESUMO
Little information is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was performed for the purpose of establishing an optimal dosage regimen in children. Sixty-four patients were divided according to CYP3A5 genotype (expression of *1 allele: EX and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n = 21), EX-R/NEX-D (n = 8), NEX-R/EX-D (n = 8) and NEX-R/NEX-D (n = 27). Results indicated that initial TAC daily dose requirement was higher among EX-R/EX-D children compared with those who did not express CYP3A5 (0.28 ± 0.10 vs. 0.19 ± 0.08 mg/kg/day, p < 0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and graft liver was a key determinant. Additionally, the EX-R/EX-D group showed significantly higher incidence of infectious complications, lower immune response and was an independent risk factor for the development of infections (odds ratio 3.86, p = 0.025). Donor CYP3A5 expression partially explains TAC dose requirement, the effect of CYP3A5 variation may influence clinical outcomes; therefore, monitoring immune response may be important for preventing risks associated with under- and over-immunosuppression.
Assuntos
Citocromo P-450 CYP3A/genética , Genótipo , Falência Hepática/genética , Falência Hepática/cirurgia , Transplante de Fígado , Tacrolimo/farmacocinética , Infecções Bacterianas/complicações , Infecções Bacterianas/genética , Pré-Escolar , China , Feminino , Humanos , Imunossupressores/farmacocinética , Lactente , Masculino , Farmacogenética , Complicações Pós-Operatórias , Análise de Regressão , Fatores de Risco , Resultado do Tratamento , Viroses/complicações , Viroses/genéticaRESUMO
BACKGROUND: A complex interaction and mutual influence exists among landscapes, cultures, and landraces, with rice culture being a typical embodiment of this relationship. The conservation of landraces operates alongside preserving traditional practices. The Xishuangbanna region stands out as a hub for the genetic diversity of landraces, boasting rich genetic resources. Despite the diverse rice resources in this region, a comprehensive and systematic study has not been undertaken. METHODS: From October to November 2023, we collected rice landraces under the on-farm conservation in 18 townships including Menghai, Mengla and Jinghong in Xishuangbanna. Employing semi-structured interviews and various methods, we investigated factors influencing the preservation and loss of rice landraces in the region. Statistical analysis was applied to the agronomic traits of collected local rice, encompassing indica or japonica, glutinous or non-glutinous, grain shape, and hull color as second category traits. The second category included quantitative traits like thousand grain weight and grain length. Rice diversity among different regions, traits, and ethnic groups was assessed using the Shannon-Wiener index. Additionally, clustering analysis via the UPGMA method depicted the distribution characteristics of the resources. RESULTS: A total of 70 rice landraces were collected in the Xishuangbanna region, each exhibiting distinct characteristics. Differences were observed across regions, trait, naming, and ethnic groups. Diversity analysis revealed that Mengla had the highest diversity, followed by Menghai, while Jinghong exhibited the lowest diversity. The second category of traits displayed broader diversity than the first, with the Dai people's glutinous rice showcasing greater diversity than other ethnic groups. Cluster analysis categorized the 70 samples into seven groups at a genetic distance of 1.15. Ethnobotanical interviews emphasized the rapid loss of rice landraces resources in Xishuangbanna, with indigenous ethnic cultures playing a vital role in the conservation of rice landraces. Dai traditions, in particular, played a crucial role in protecting glutinous rice resources, showcasing a mutual dependence between Dai culture and glutinous rice. CONCLUSIONS: The rich natural environment and diverse ethnic cultures in Xishuangbanna have given rise to various rice landraces. The Dai, primary cultivators of glutinous rice with higher diversity, intertwine their traditional ethnic culture with the conservation of glutinous rice resources. At the same time, the preserving glutinous rice resources promotes the inheritance of Dai ethnic culture. However, rice landraces are facing the risk of loss. Hence, collecting and documenting rice landraces is crucial. Encourage local communities to sustain and expand their cultivation, promoting on-farm conservation. These measures contribute valuable germplasm and genes for rice breeding and serve as a means of cultural preservation.