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BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.
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Ductos Biliares Extra-Hepáticos , Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/complicações , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/complicações , Pessoa de Meia-Idade , Prognóstico , Ductos Biliares Extra-Hepáticos/cirurgia , Ductos Biliares Extra-Hepáticos/patologia , Trombose/cirurgia , Trombose/etiologia , Trombose/patologia , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/mortalidade , Idoso , AdultoRESUMO
Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genômica , Resultado do Tratamento , Fenótipo , MutaçãoRESUMO
Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.
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Dysregulation of RNA-binding proteins (RBP) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in patients with TNBC. SNRPC ablation significantly impaired the proliferation, migration, and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2, and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1-ß-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC. SIGNIFICANCE: A functional CRISPR screen identifies SNRPC as an RNA-binding protein that promotes the aggressiveness of breast cancer by facilitating Pol II-controlled transcription of oncogenes.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Prognóstico , RNA Polimerase II/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Ribonucleoproteína Nuclear Pequena U1/genética , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.
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Criança , Masculino , Humanos , Feminino , Pré-Escolar , Adolescente , Doença de Crohn , Doenças Inflamatórias Intestinais , Colo , Inflamação , Colonoscopia , Glicoproteínas , Proteínas WntRESUMO
Objective: To explore the efficacy and safety of endoscopic diaphragm incision in pediatric congenital duodenal diaphragm. Methods: Eight children with duodenal diaphragm treated by endoscopic diaphragm incision in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from October 2019 to May 2022 were enrolled in this study. Their clinical data including general conditions, clinical manifestations, laboratory and imaging examinations, endoscopic procedures and outcomes were retrospectively analyzed. Results: Among the 8 children, 4 were males and 4 females. The diagnosis was confirmed at the age of 6-20 months; the age of onset was 0-12 months and the course of disease was 6-18 months. The main clinical manifestations were recurrent non-biliary vomiting, abdominal distension and malnutrition. One case complicated with refractory hyponatremia was first diagnosed with atypical congenital adrenal hyperplasia in the endocrinology department. After treatment with hydrocortisone, the blood sodium returned to normal, but vomiting was recurrent. One patient underwent laparoscopic rhomboid duodenal anastomosis in another hospital but had recurred vomiting after the operation, who was diagnosed with double duodenal diaphragm under endoscope. No other malformations were found in all the 8 cases. The duodenal diaphragm was located in the descending part of the duodenum, and the duodenal papilla was located below the diaphragm in all the 8 cases. Three cases had the diaphragm dilated by balloon to explore the diaphragm opening range before diaphragm incision; the other 5 had diaphragm incision performed after probing the diaphragm opening with guide wire. All the 8 cases were successfully treated by endoscopic incision of duodenal diaphragm, with the operation time of 12-30 minutes. There were no complications such as intestinal perforation, active bleeding or duodenal papilla injury. At one month of follow-up, their weight increased by 0.4-1.5 kg, with an increase of 5%-20%. Within the postoperative follow-up period of 2-20 months, all the 8 children had duodenal obstruction relieved, without vomiting or abdominal distension, and all resumed normal feeding. Gastroscopy reviewed at 2-3 months after the operation in 3 cases found no deformation of the duodenal bulbar cavity, and the mucosa of the incision was smooth, with a duodenal diameter of 6-7 mm. Conclusion: Endoscopic diaphragm incision is safe, effective and less invasive in pediatric congenital duodenal diaphragm, with favorable clinical applicability.
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Masculino , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Tórax , Endoscopia , Exame Físico , Hiperplasia Suprarrenal CongênitaRESUMO
Immune checkpoint inhibitors exhibit limited response rates in patients with triple-negative breast cancer (TNBC), suggesting that additional immune escape mechanisms may exist. Here, we performed two-step customized in vivo CRISPR screens targeting disease-related immune genes using different mouse models with multidimensional immune-deficiency characteristics. In vivo screens characterized gene functions in the different tumor microenvironments and recovered canonical immunotherapy targets such as Ido1. In addition, functional screening and transcriptomic analysis identified Lgals2 as a candidate regulator in TNBC involving immune escape. Mechanistic studies demonstrated that tumor cell-intrinsic Lgals2 induced the increased number of tumor-associated macrophages, as well as the M2-like polarization and proliferation of macrophages through the CSF1/CSF1R axis, which resulted in the immunosuppressive nature of the TNBC microenvironment. Blockade of LGALS2 using an inhibitory antibody successfully arrested tumor growth and reversed the immune suppression. Collectively, our results provide a theoretical basis for LGALS2 as a potential immunotherapy target in TNBC.
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Neoplasias de Mama Triplo Negativas , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Galectina 2/genética , Humanos , Imunoterapia/métodos , Camundongos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Microambiente Tumoral/genéticaRESUMO
The mechanism of the deactivation and regeneration of PtSn intermetallic compound nanoparticle (iNP) catalysts was studied by in situ TEM investigation. Our study reveals the reversible dynamic structural transition of the iNPs during deactivation and regeneration, which provides a direct correlation between the atomic structure and the catalytic activity of the iNPs.
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Triple-negative breast cancer (TNBC) remains an unmet medical challenge. We investigated metabolic dysregulation in TNBCs by using our multi-omics database (n = 465, the largest to date). TNBC samples were classified into three heterogeneous metabolic-pathway-based subtypes (MPSs) with distinct metabolic features: MPS1, the lipogenic subtype with upregulated lipid metabolism; MPS2, the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism; and MPS3, the mixed subtype with partial pathway dysregulation. These subtypes were validated by metabolomic profiling of 72 samples. These three subtypes had distinct prognoses, molecular subtype distributions, and genomic alterations. Moreover, MPS1 TNBCs were more sensitive to metabolic inhibitors targeting fatty acid synthesis, whereas MPS2 TNBCs showed higher sensitivity to inhibitors targeting glycolysis. Importantly, inhibition of lactate dehydrogenase could enhance tumor response to anti-PD-1 immunotherapy in MPS2 TNBCs. Collectively, our analysis demonstrated the metabolic heterogeneity of TNBCs and enabled the development of personalized therapies targeting unique tumor metabolic profiles.
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Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Humanos , Imunoterapia , Masculino , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/terapia , Células Tumorais CultivadasRESUMO
BACKGROUND: The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear. METHODS: Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications. RESULTS: Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors. CONCLUSIONS: Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.
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Neoplasias de Mama Triplo Negativas , Povo Asiático/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Humanos , Mutação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
OBJECTIVES@#To study the predictive factors for glucocorticoid therapy by analyzing the association between the clinical features and treatment regimens in children with eosinophilic gastroenteritis.@*METHODS@#A retrospective analysis was performed on the medical data of 182 children with eosinophilic gastroenteritis who were admitted to Guangzhou Women and Children's Medical Center from January 2012 to December 2020. According to whether glucocorticoids were used, these children were divided into a glucocorticoid treatment group and a control group. The two groups were compared in terms of age, history of allergy, clinical symptoms, laboratory examination results, endoscopic findings, and pathological results of gastrointestinal mucosa. A multivariate logistic regression analysis was performed for the results with statistical significance.@*RESULTS@#Of the 182 children, 36 (19.8%) received glucocorticoid therapy. The rates of hematochezia, anemia, and mucosal ulceration/luminal stenosis under endoscopy and the mucosal eosinophil infiltration count were significantly higher in the glucocorticoid treatment group than those in the control group (@*CONCLUSIONS@#Mucosal ulceration/luminal stenosis under endoscopy or a significant increase in the mucosal eosinophil infiltration count based on pathology suggests that glucocorticoid therapy can be considered in children with eosinophil gastroenteritis.
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Criança , Feminino , Humanos , Enterite/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Gastrite , Glucocorticoides/uso terapêutico , Estudos RetrospectivosRESUMO
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.
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Povo Asiático/genética , Neoplasias da Mama , Terapia de Alvo Molecular , Mutação , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , China , Gerenciamento de Dados , Feminino , Marcadores Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neurofibromina 2/genética , Oncogenes , Medicina de Precisão , Estudos Prospectivos , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Rationale: Paclitaxel resistance is a major concern when treating triple-negative breast cancer (TNBC) patients. We aimed to identify candidates causing paclitaxel resistance and explore their significance in TNBC therapeutics. Methods: A genome-wide CRISPR screening, integrated with transcriptome analyses, was performed to identify candidates involved in paclitaxel-resistant TNBCs. Cell proliferation, cytotoxicity, immunofluorescent staining, and xenograft assays were conducted to verify the phenotypes of paclitaxel resistance induced by candidate genes, both in vitro and in vivo. RNA sequencing, Western blotting, and chromatin immunoprecipitation assays were used to explore the underlying mechanisms. Results: MEF2-interacting transcriptional repressor (MITR), the truncated isoform of histone deacetylase 9 (HDAC9) lacking the deacetylation domain, was enriched in paclitaxel-resistant cells. Elevated MITR expression resulted in increased interleukin-11 (IL11) expression and activation of downstream JAK/STAT3 signaling. Mechanistically, MITR counteracted MEF2A-induced transcriptional suppression of IL11, ultimately causing paclitaxel resistance. By contrast, pharmacological inhibition of JAK1/2 by ruxolitinib reversed paclitaxel resistance both in vitro and in vivo. Conclusion: Our in vitro and in vivo genetic and cellular analyses elucidated the pivotal role of MITR/MEF2A/IL11 axis in paclitaxel resistance and provided a novel therapeutic strategy for TNBC patients to overcome poor chemotherapy responses.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Histona Desacetilases/metabolismo , Paclitaxel/farmacologia , Proteínas Repressoras/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Células HEK293 , Histona Desacetilases/genética , Humanos , Interleucina-11/genética , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Estimativa de Kaplan-Meier , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Camundongos , Nitrilas , Paclitaxel/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas , RNA-Seq , Proteínas Repressoras/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Nerve reconstructive surgery induces a transient loss and a prolonged and a gradual return of sensory inputs to the brain. It is unknown whether, following this massive peripheral denervation, the brain will experience a prolonged period of severe, intrinsic dysfunction. OBJECTIVE: We aim to investigate the mechanisms of return of processing function in cortical neurons. METHODS: We used the whisker model in rats to evaluate the functional recovery in the somatosensory cortex after a nerve reconstruction surgery. Multi-unit recording in the barrel cortex was performed in lightly anesthetized rats while their whiskers were stimulated by a whisker stimulator. RESULTS: We observed a loss of neuronal responses to whisker stimulation 1 week after surgery, which started to recover 2 weeks after surgery. Following the surgery, only 11.8% of units had principle whiskers (PWs) returned to their original status while 17.7% had PWs different from their original status, indicating the effect of aberrant reinnervation on the whisker response map. CONCLUSIONS: Robust neuronal responses to sensory stimulation even when only sparse sensory inputs are available in the early recovery phase. During this phase, aberrant reinnervation induces disorganized whisker tuning, a finding that might be account for the hypoesthesia and paresthesia during early recovery after nerve reconstruction.
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Nervo Maxilar/fisiopatologia , Procedimentos de Cirurgia Plástica , Recuperação de Função Fisiológica/fisiologia , Córtex Somatossensorial/fisiopatologia , Vibrissas/inervação , Vibrissas/fisiologia , Animais , Estimulação Física , RatosRESUMO
Circular RNAs (circRNAs) are emerging species of mRNA splicing products with largely unknown functions. Although several computational pipelines for circRNA identification have been developed, these methods strictly rely on uniquely mapped reads overlapping back-splice junctions (BSJs) and lack approaches to model the statistical significance of the identified circRNAs. Here, we reported a systematic computational approach to identify circRNAs by simultaneously utilizing BSJ overlapping reads and discordant BSJ spanning reads to identify circRNAs. Moreover, we developed a novel procedure to estimate the P-values of the identified circRNAs. A computational cross-validation and experimental validations demonstrated that our method performed favorably compared to existing circRNA detection tools. We created a standalone tool, CircRNAFisher, to implement the method, which might be valuable to computational and experimental scientists studying circRNAs.
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Biologia Computacional/métodos , RNA/análise , Análise de Sequência de RNA/métodos , Algoritmos , Linhagem Celular Tumoral , Fibroblastos/química , Humanos , RNA/genética , RNA/isolamento & purificação , RNA CircularRESUMO
BACKGROUND: Voice and swallowing impairments can impact on both quality of life and survival. Unilateral vocal fold paralysis (UVFP) as a result of distant metastasis can cause breathy voice and aspiration. The purpose of this study is to develop and evaluate a less invasive and effective alternative therapy for UVFP. METHODS: This was a retrospective review of prospectively enrolled patients at a tertiary referral center in Taiwan. Among a cohort of 177 patients who received intracordal hyaluronate injections, 2 had UVFP from distant metastasis and met the inclusion criteria. Vocal cord motion was recorded by videostroboscopy, and the normalized glottal gap area was measured. Voice quality, defined by speech language pathologists, and swallowing status were compared, and immediate complications after the injection were investigated. RESULTS: Two patients with UVFP with M1 lesions (both lung) accepted the procedure. The glottal gap area was significantly improved 1 month after in-office hyaluronate injection. Voice quality and aspiration were also improved. No immediate complications were noted in either patient. CONCLUSIONS: In-office intracordal hyaluronate injection is a safe and effective treatment for UVFP, providing a palliative method to help maintain the patient's voice and quality of life.
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Hialuronoglucosaminidase/uso terapêutico , Neoplasias Laríngeas/complicações , Cuidados Paliativos/métodos , Paralisia das Pregas Vocais/tratamento farmacológico , Adulto , Idoso , Assistência Ambulatorial , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Neoplasias Laríngeas/secundário , Neoplasias Laríngeas/cirurgia , Laringoplastia/métodos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Medição de Risco , Taiwan , Centros de Atenção Terciária , Resultado do Tratamento , Paralisia das Pregas Vocais/fisiopatologiaRESUMO
Thoracic-surgery-related unilateral vocal fold paralysis (UVFP) may cause severe morbidity and can cause profound functional impairment and psychosocial stress in patients with pre-existing thoracic diseases. In-office intracordal hyaluronate (HA) injections have recently been applied to improve voice and quality of life in patients with vocal incompetence, but their effect on thoracic-surgery-related UVFP remains inconclusive. We therefore conducted a prospective study to clarify the effect of early HA injection on voice and quality of life in patients with thoracic-surgery-related UVFP. Patients with UVFP within 3 months after thoracic surgery who received office-based HA injection were recruited. Quantitative laryngeal electromyography, videolaryngostroboscopy, voice-related life quality (voice outcome survey), laboratory voice analysis, and health-related quality of life (SF-36) were evaluated at baseline, and at 1 month postinjection. A total of 104 consecutive patients accepted office-based HA intracordal injection during the study period, 34 of whom were treated in relation to thoracic surgery and were eligible for inclusion. Voice-related life quality, voice laboratory analysis, and most generic quality of life domains were significantly improved at 1 month after in-office HA intracordal injection. No HA-related complications were reported. Single office-based HA intracordal injection is a safe and effective treatment for thoracic-surgery-related UVFP, resulting in immediate improvements in patient quality of life, voice quality, and swallowing ability.
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Ácido Hialurônico/administração & dosagem , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Viscossuplementos/administração & dosagem , Paralisia das Pregas Vocais/tratamento farmacológico , Paralisia das Pregas Vocais/etiologia , Adulto , Idoso , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Viscossuplementos/uso terapêutico , VozRESUMO
Lymphedema is a chronic disorder characterized by lymph stasis in the subcutaneous tissue. Lymphatic fluid contains several components including hyaluronic acid and has many important properties. Over the past few years, significant research has been performed to identify an ideal tissue to implant as a filler. Because of its unique composition, fat harvested from the lymphedema tissue is an interesting topic for investigation and has significant potential for application as a filler, particularly in facial rejuvenation. Over a 36-month period, we treated and assessed 8 patients with lymphedematous limbs who concurrently underwent facial rejuvenation with lymphedema fat (LF). We conducted a pre- and post-operative satisfaction questionnaire survey and a histological assessment of the harvested LF fat. The overall mean general appearance score at an average of 6 months after the procedure was 7.2+/-0.5, demonstrating great improvement. Patients reported significant improvement in their skin texture with a reading of 8.5+/-0.7 and an improvement in their self-esteem. This study demonstrates that LF as an ideal autologous injectable filler is clinically applicable and easily available in patients with lymphedema. We recommend the further study and clinical use of this tissue as it exhibits important properties and qualities for future applications and research.
Assuntos
Humanos , Tecido Adiposo , Estética , Extremidades , Ácido Hialurônico , Linfedema , Rejuvenescimento , Pele , Tela Subcutânea , Transplantes , Inquéritos e QuestionáriosRESUMO
<p><b>OBJECTIVE</b>To evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children.</p><p><b>METHOD</b>A total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment.</p><p><b>RESULT</b>Finally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05).</p><p><b>CONCLUSION</b>The 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.</p>
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Administração Oral , Amoxicilina , Antibacterianos , Antiulcerosos , Testes Respiratórios , Métodos , Claritromicina , Esquema de Medicação , Quimioterapia Combinada , Infecções por Helicobacter , Tratamento Farmacológico , Helicobacter pylori , Metronidazol , Testes de Sensibilidade Microbiana , Omeprazol , Fatores de Tempo , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To investigate the imaging features of synovial tuberculosis of sheath of wrist.</p><p><b>METHODS</b>Three patients of synovial tuberculosis of sheath of wrist underwent surgical operation from Oct. 2002 to Oct. 2009 included 2 males and 1 female, the age of 48, 67, 76 years respectivly. X-rays of 3 patients, CTs of 2 patients and MRI of 1 patient were retrospectively analyzed and the relevant literature were reviewed.</p><p><b>RESULTS</b>There were 3 cases with the soft tissue mass in the palm side of wrist, the section was unclear. There were no osteoporosis and no changes of bone destruction. There was 1 case with the punctate calcification in the soft tissue. MRI showed the embedded cystic mass of flexor tendon and "8" shape in carpal tunnel pressure, and showed abnormal signal (T1 low-signal, T2 slightly higher signal), a small part of the internal point showed high signal. CT showed the synovial membrane were obvious thickening and enhanced, corpus liberum in tendon sheath were no obvious strengthening.</p><p><b>CONCLUSION</b>Synovial tuberculosis of sheath of wrist has certain characteristics on radiographic image. The MRI has more clinical value than X-ray and CT.</p>