With the rapid spread of electronic medical records and the arrival of medical big data era, the application of natural language processing technology in biomedicine has become a hot research topic.
...In this paper, firstly, BiLSTM-CRF model is applied to medical named entity recognition on Chinese electronic medical record. According to the characteristics of Chinese electronic medical records, obtain the low-dimensional word vector of each word in units of sentences. And then input the word vector to BiLSTM to realize automatic extraction of sentence features. And then CRF performs sentence-level word tagging. Secondly, attention mechanism is added between the BiLSTM and the CRF to construct Attention-BiLSTM-CRF model, which can leverage document-level information to alleviate tagging inconsistency. In addition, this paper proposes an entity auto-correct algorithm to rectify entities according to historical entity information. At last, a drug dictionary and post-processing rules are well-built to rectify entities, to further improve performance.
The final F1 scores of the BiLSTM-CRF and Attention-BiLSTM-CRF model on given test dataset are 90.15 and 90.82% respectively, both of which are higher than 89.26%, which is the best F1 score on the test dataset except ours.
Our approach can be used to recognize medical named entity on Chinese electronic medical records and achieves the state-of-the-art performance on the given test dataset.
Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in ...improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results.
Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population).
After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval CI 67.7–79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8–69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9–87.7) than in the CCRT alone group (73.1%, 95% CI 67.2–79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% 39/238 versus 9.7% 23/238, p = 0.029).
IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.
•IC followed by CCRT improved not only DMFS and DFS, but also OS at 5 years in patients with locoregionally advanced NPC.•The addition of cisplatin and fluorouracil induction chemotherapy did not significantly increase late toxicities.•IC followed by CCRT can be recommended for patients with locoregionally advanced NPC.
Objectives/Hypothesis
The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non‐real‐time image‐guided transnasal endoscopic ...fine‐needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions.
Study Design
The effectiveness evaluation of diagnostic methods.
Methods
Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated.
Results
The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884–1.00, P < .001). No severe complications occurred after FNAB.
Conclusions
FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application.
Level of Evidence
4 Laryngoscope, 131:1798–1804, 2021
To evaluate safety and efficacy of one- vs. two-session radiofrequency ablation (RFA) of parathyroid hyperplasia for patients with secondary hyperparathyroidism (SHPT) and to compare the outcome of ...both methods on hypocalcemia. Patients with secondary hyperparathyroidism underwent ultrasound guided RFA of parathyroid hyperplasia. Patients were alternately assigned to either group 1 (n = 28) with RFA of all 4 glands in one session or group 2 (n = 28) with RFA of 2 glands in a first session and other 2 glands in a second session. Serum parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) values were measured at a series of time points after RFA. RFA parameters, including operation duration and ablation time and hospitalization length and cost, were compared between the two groups. Mean PTH decreased in group 1 from 1865.18 ± 828.93 pg/ml to 145.72 ± 119.27 pg/ml at 1 day after RFA and in group 2 from 2256.64 ± 1021.72 pg/ml to 1388.13 ± 890.15 pg/ml at 1 day after first RFA and to 137.26 ± 107.12 pg/ml at 1 day after second RFA. Group 1's calcium level decreased to 1.79 ± 0.31 mmol/L at day 1 after RFA and group 2 decreased to 1.89 ± 0.26 mmol/L at day 1 after second session RFA (P < 0.05). Multivariate analysis showed that hypocalcemia was related to serum ALP. Patients with ALP ≥ 566 U/L had lower calcium compared to patients with ALP < 566 U/L up to a month after RFA (P < 0.05). Group 1's RFA time and hospitalization were shorter and had lower cost compared with Group 2. US-guided RFA of parathyroid hyperplasia is a safe and effective method for treating secondary hyperparathyroidism. Single-session RFA was more cost-effective and resulted in a shorter hospital stay compared to two sessions. However, patients with two-session RFA had less hypocalcemia, especially those with high ALP.
To compare intensity‐modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II‐IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with ...stage II–IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well‐balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well‐balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3‐year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco‐regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4–4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related‐skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP‐IMRT combination for maximizing survival for patients with stage II‐IVb NPC.
What's new?
Standard treatment for nasopharyngeal carcinoma (NPC) that has spread to lymph nodes in the head and neck entails concurrent cisplatin (CDDP) and intensity‐modulated radiotherapy (IMRT). High toxicity rates, however, limit the utility of this approach. The present study examines an alternative strategy: cetuximab (CTX) and nimotuzumab (NTZ) plus IMRT. No differences in risk of disease progression, relapse, metastasis or death were observed in a direct comparison between CDDP plus IMRT and CTX/NTZ plus IMRT in NPC patients. Both regimens were associated with hematologic toxicities and with toxicities targeting different tissues, warranting further investigation of side effects specific to CTX/NTZ.
Abstract Multifunctional nanocarriers are increasingly promising for disease treatment aimed to regulate multiple pathological dysfunctions and overcome barriers in drug delivery. Here we develop a ...multifunctional nanocarrier for Alzheimer's disease (AD) treatment by achieving therapeutic gene and peptide co-delivery to brain based on PEGylated dendrigraft poly- l -lysines (DGLs) via systemic administration. The dendritic amine-rich structure of DGLs provides plenty reaction sites and positive charge for drug loading. Successful co-delivery of drugs overcoming the blood–brain barrier by brain-targeted ligand modification was demonstrated both in vitro and in vivo . The pharmacodynamics study of the system following multiple-dosing treatment was verified in transgenic AD mice. Down-regulation of the key enzyme in amyloid-β formation was achieved by delivering non-coding RNA plasmid. Simultaneous delivery of the therapeutic peptide into brain leads to reduction of neurofibrillary tangles. Meanwhile, memory loss rescue in AD mice was also observed. Taken together, the multifunctional nanocarrier provides an excellent drug co-delivery platform for brain diseases.
Mesenchymal stem cells (MSCs) stabilise endothelial barrier function in acute lung injury via paracrine hepatocyte growth factor (HGF). Vascular endothelial growth factor (VEGF), which is secreted by ...MSCs, is another key regulator of endothelial permeability; however, its role in adjusting permeability remains controversial. In addition, whether an interaction occurs between HGF and VEGF, which are secreted by MSCs, is not completely understood.
We introduced a co-cultured model of human pulmonary microvascular endothelial cells (HPMECs) and MSC conditioned medium (CM) collected from MSCs after 24 h of hypoxic culture. The presence of VEGF and HGF in the MSC-CM was neutralised by anti-VEGF and anti-HGF antibodies, respectively. To determine the roles and mechanisms of MSC-secreted HGF and VEGF, we employed recombinant humanised HGF and recombinant humanised VEGF to co-culture with HPMECs. Additionally, we employed the RhoA inhibitor C3 transferase and the Rac1 inhibitor NSC23766 to inhibit the activities of RhoA and Rac1 in HPMECs treated with MSC-CM or VEGF/HGF with the same dosage as in the MSC-CM. Then, endothelial paracellular and transcellular permeability was detected. VE-cadherin, occludin and caveolin-1 protein expression in HPMECs was measured by western blot. Adherens junction proteins, including F-actin and VE-cadherin, were detected by immunofluorescence.
MSC-CM treatment significantly decreased lipopolysaccharide-induced endothelial paracellular and transcellular permeability, which was significantly inhibited by pretreatment with HGF antibody or with both VEGF and HGF antibodies. Furthermore, MSC-CM treatment increased the expression of the endothelial intercellular adherence junction proteins VE-cadherin and occludin and decreased the expression of caveolin-1 protein. MSC-CM treatment also decreased endothelial apoptosis and induced endothelial cell proliferation; however, the effects of MSC-CM treatment were inhibited by pretreatment with HGF antibody or with both HGF and VEGF antibodies. Additionally, the effects of MSC-CM and VEGF/HGF on reducing endothelial paracellular and transcellular permeability were weakened when HPMECs were pretreated with the Rac1 inhibitor NSC23766.
HGF secreted by MSCs protects the endothelial barrier function; however, VEGF secreted by MSCs may synergize with HGF to stabilise endothelial cell barrier function. Rac1 is the pathway by which MSC-secreted VEGF and HGF regulate endothelial permeability.
Hepatocellular carcinoma (HCC), one of the most common lethal diseases in the world, has a 5-year survival rate of only 7%. Hepatocellular carcinoma has no symptoms in the early stage but obvious ...symptoms in the late stage, leading to delayed diagnosis and reduced treatment efficacy. In recent years, as the scope of HCC research has increased in depth, the clinical development and application of molecular targeted drugs and immunotherapy drugs have brought new breakthroughs in HCC treatment. Targeted therapy drugs for HCC have high specificity, allowing them to selectively kill tumor cells and minimize damage to normal tissues. At present, these targeted drugs are mainly classified into 3 categories: small molecule targeted drugs, HCC antigen-specific targeted drugs, and immune checkpoint targeted drugs. This article reviews the latest research progress on the targeted drugs for HCC.
IMPORTANCE: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of ...relapse and death are needed. OBJECTIVE: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. INTERVENTIONS: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. RESULTS: Among 443 women who were randomized, 434 were included in the full analysis set (mean SD age, 46 9.9 years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio HR for risk of recurrence or death, 0.64 95% CI, 0.42-0.95; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 95% CI, 0.38-0.92; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 95% CI, 0.46-1.13; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. CONCLUSIONS AND RELEVANCE: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01112826
Objectives
To evaluate the relationship between contrast-enhanced (CE) ultrasound Liver Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and ...their histopathological component predominance, and to determine if the CEUS LI-RADS category can be used to predict the patient’s survival after surgical resection.
Methods
Between January 2011 and December 2018, medical records and CEUS of patients with pathologically proven cHCC-CCA were studied. The predominance of hepatocellular carcinoma (HCC)/intrahepatic cholangiocarcinoma (ICC) component of cHCC-CCA was analyzed by histopathology. The proportion of HCC-predominant cHCC-CCA in different LI-RADS category was compared by using Fisher’s exact test. Factors affecting tumor recurrence were analyzed by Cox proportional hazard model. Disease-free survival (DFS) was estimated by using Kaplan-Meier survival curve and compared by log-rank test.
Results
The study included 37 cHCC-CCA patients (33 men, 4 women; average age, 50.4 ± 11.0 years) and 37 nodules (mean diameter, 6.1 ± 3.9 cm). According to CEUS LI-RADS, 62.2% (23/37), 18.9% (7/37), and 18.9% (7/37) of cHCC-CCA were classified as LR-M, LR-5, and LR-TIV, respectively. The ratio of HCC predominance in LR-5 was 100% (10/10) vs 81.5% (22/27) in the LR-M group (
p
= 0.591). In our population, LR-5 patients had longer DFS than LR-M and LR-TIV patients combined (median DFS: 18.0 vs 6.4 months,
p
= 0.016). Multiple lesions (hazard ratio, 3.1;
p
= 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1;
p
= 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7;
p
= 0.011) showed independent association with shorter DFS.
Conclusion
cHCC-CCA characterized as LR-5 on CEUS tend to represent HCC-predominant tumors with significantly longer disease-free survival compared to cHCC-CCA categorized as LR-M and LR-TIV.
Key Points
•
By using the American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), majority (30/37, 81.1%) of cHCC-CCA tumors were classified as LR-M or LR-TIV and only 18.9% (7/30) of cHCC-CCA were categorized as LR-5.
•
Patients with CEUS LR-5 cHCC-CCA had statistically significant longer disease-free time than those with LR-M and TIV cHCC-CCA (median DFS: 18.0 vs 6.4 months, p = 0.016).
•
Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS.
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