RESUMO
Electronic health records (EHRs) have been widely used and are gradually replacing paper records. Therefore, extracting valuable information from EHRs has become the focus and hotspot of current research. Clinical named entity recognition (CNER) is an important task in information extraction. Most current research methods used standard supervised learning approaches to fine-tune pre-trained language models (PLMs), which require a large amount of annotated data for model training. However, in realistic medical scenarios, annotated data are scarce, especially in the healthcare field. The process of annotating data in real clinical settings is time-consuming and labour-intensive. In this paper, a language inference-based learning method (LANGIL) is proposed to study clinical NER tasks with limited annotated samples, i.e., in low-resource clinical scenarios. A method based on prompt learning is designed to reformulate the entity recognition task into a language inference-based task. Differing from the standard fine-tuning method, the approach introduced in this paper does not design the additional network layers that train from scratch. This alleviates the gap between pre-training tasks and downstream tasks, allowing the comprehension capabilities of PLMs to be leveraged under the condition of limited training samples. The experiments on four Chinese clinical named entity recognition datasets showed that LANGIL achieves significant improvements in F1-score compared to the former method.
Assuntos
Armazenamento e Recuperação da Informação , Idioma , Cavalos , Animais , Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , ChinaRESUMO
To assure faithful chromosome segregation, cells make use of the spindle assembly checkpoint, which can be activated in aneuploid cancer cells. In this study, the efficacies of inhibiting polo-like kinase 1 (PLK1) on the radiosensitization of non-small-cell lung cancer (NSCLC) cells were studied. Clonogenic survival assay was performed to identify the effects of the PLK1 inhibitor on radiosensitivity within NSCLC cells. Mitotic catastrophe assessment was used to measure the cell death and histone H2AX protein (γH2AX) foci were utilized to assess the DNA double-strand breaks (DSB). The transcriptome was analyzed via unbiased profiling of microarray expression. The results showed that the postradiation mitotic catastrophe induction and the DSB repair were induced by PLK1 inhibitor BI-6727, leading to an increase in the radiosensitivity of NSCLC cells. BI-6727 in combination with radiation significantly induced the delayed tumor growth. PLK1-silenced NSCLC cells showed an altered mRNA and protein expression related to DNA damaging, replication, and repairing, including the DNA-dependent protein kinase (DNAPK) and topoisomerase II alpha (TOPO2A). Furthermore, inhibition of PLK1 blocked 2 important DNA repair pathways. To summarize, our study showed PLK1 kinase as an option in the therapy of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas de Ciclo Celular/antagonistas & inibidores , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Segregação de Cromossomos/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Pteridinas/farmacologia , Quinase 1 Polo-LikeRESUMO
Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21-0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38-0.92; p = 0.020), postoperative pain (95% CI 0.13-0.33; p < 0.001), and surgery-related complications (95% CI 0.19-0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84-3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS.Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx .
Assuntos
Hiperidrose , Ablação por Radiofrequência , Humanos , Resultado do Tratamento , Cirurgia Torácica Vídeoassistida/efeitos adversos , Hiperidrose/cirurgia , Ablação por Radiofrequência/efeitos adversos , Simpatectomia/efeitos adversos , MãosRESUMO
Lung cancer is an extremely heterogeneous disease, and its treatment remains one of the most challenging tasks in medicine. Few existing laboratory lung cancer models can faithfully recapitulate the diversity of the disease and predict therapy response. Here, we establish 12 patient-derived organoids from the most common lung cancer subtype, lung adenocarcinoma (LADC). Extensive gene and histopathology profiling show that the tumor organoids retain the histological architectures, genomic landscapes, and gene expression profiles of their parental tumors. Patient-derived lung cancer organoids are amenable for biomarker identification and high-throughput drug screening in vitro. This study should enable the generation of patient-derived lung cancer organoid lines, which can be used to further the understanding of lung cancer pathophysiology and to assess drug response in personalized medicine.
RESUMO
Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5-7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α (hypoxia-inducible factor 1α overexpression lentivirus), gel (pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α (pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups (in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area (labeled by CD31 around avulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii (identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.