Discovery and biological evaluation of a new type of dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase from ethnomedicinal plant Dactylicapnos scandens.

The root of Dactylicapnos scandens (D.Don.) Hutch (Papaveraceae), one of the most famous ethno-medicinal plants from the Bai communities in P. R. China, is used to treat various inflammations and tumours. Bioassay-guided phytochemical research on D. scandens followed by semi-synthesis led to a series of undescribed tetrahydroisoquinoline alkaloids with dual inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). The previously undescribed dark-green alkaloid dactycapnine A exhibited the best dual inhibitor effects among the identified compounds. Structure-activity relationship analysis revealed the importance of the base skeleton with a hyperconjugation system. The performed semi-synthesis further yielded bioactive dimeric and trimeric compounds with hyperconjugated systems. Performed STD NMR experiments disclosed direct interactions between dactycapnine A and IDO1/TDO. Inhibition kinetics indicated dactycapnine A as a mixed-type dual inhibitor. These findings provided a possible explanation for the anticancer properties of the ethno-medicinal plant species D. scandens.

Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. PURPOSE: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. STUDY DESIGN AND METHODS: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. RESULTS: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. CONCLUSION: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.

Study on the feature of cortical auditory evoked potential under different auditory tasks in cochlear implant children / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the variation regularity and influencing factors of cortical auditory evoked potential (CAEP) evoked by pure tone, syllable and tone stimuli in cochlear implant (CI) children. Methods: Cortical auditory evoked potential (CAEP) responses were collected from 46 CI children in the sound field. Pure tones with frequencies of 1 kHz and 2 kHz were used as the standard and the deviant respectively in the pure tone stimulation condition. The Chinese Mandarin tokens/ba/-/pa/and/ba1/-/ba4/pairs were used as the stimuli respectively in the syllable and tone stimulation condition. The latency, amplitude and presence rate of P1 and mismatch negative(MMN) were obtained and the correlation between the difficulty of auditory task, the age of hearing month, the duration of severe-profound hearing loss, the wearing history of hearing aid before CI, the hearing threshold of the better ear before CI and the latency and amplitude of P1 and MMN were analyzed. All statistical analyses and figures were conducted using SPSS 25.0. Results: The P1 presence rate of pure tone, syllable and tone group was 100% (17/17), 100% (13/13) and 75.0% (12/16), respectively, with significant difference (χ²=8.214, P=0.016). There was significant difference between pure tone group and tone group (χ²=4.836, P=0.028), but no significant difference between pure tone group and syllable group, syllable group and tone group. The MMN presence rate of pure tone, syllable and tone group was 94.1% (16/17), 84.6% (11/13) and 62.5% (10/16), respectively, but no significant difference among the three groups with different auditory tasks(χ²=0.066, P=0.066). No significant difference was observed among the three groups of different auditory tasks in the latency and amplitude of P1 and MMN. Multiple linear regression analysis showed that the latency of P1 was positively correlated with the difficulty of auditory task and the hearing threshold of the better ear before CI, and negatively correlated with hearing age and the history of hearing aid before CI. The latency of MMN was positively correlated with the difficulty of auditory task, and negatively correlated with hearing age. Conclusions: The P1 presence rate of pure tone auditory task is significantly higher than that of tone auditory task. The difficulty of auditory task, hearing age, the history of hearing aid before CI, and the hearing threshold of the better ear before CI has significant effects on the P1 latency. The difficulty of auditory task and hearing age has significant effects on the MMN latency.

Exploration and practice of " apprenticeship" precision training for pediatricians at primary level / 中华医院管理杂志

Establishing a targeted and suitable professional healthcare training model for pediatricians at primary level and exploring an effective, sustainable and innovative strategy for talent training are required in caring for children at large. The current study explored the methods and efficacy of " apprenticeship" mode originated from traditional Chinese medicine practice in primary pediatricians training. It is suggested that based on the framework of pediatric alliance, the " apprenticeship" mode could establish a fixed and precise one-to-one teaching mode in a short period, form a close, standard and persistent training system for talented pediatricians, thus effectively improving primary pediatric health care service.

Exploring an proactive model for pediatric integration medical service in Beijing-Tianjin-Hebei region / 中华医院管理杂志

Beijing-Tianjin-Hebei region is the " Capital Circle Area" in China, holding a strategic position and importance. The authors analyzed the medical and health service bottlenecks problems incurred by the shortage and unequal distribution of pediatric medical resources to be solved urgently. On such basis, this article introduced the experience of Beijing Children′s Hospital in a top-level design targeting at building a collaborative integrated health service system to meet children′s health requirements. The hospital created four types of proactive medical collaborative innovation, including a managed type, collaborative development type, technical support type and medical alliance type, aiming at providing a diversified Beijing-Tianjin-Hebei Integration proactive medical service model. These efforts are designed to relieve the structural setback of supply and demand of pediatric medical services and better children′s health and families′ welfare.

Discrimination of raw and processed Dipsacus asperoides by near infrared spectroscopy combined with least squares-support vector machine and random forests.

Most herbal medicines could be processed to fulfill the different requirements of therapy. The purpose of this study was to discriminate between raw and processed Dipsacus asperoides, a common traditional Chinese medicine, based on their near infrared (NIR) spectra. Least squares-support vector machine (LS-SVM) and random forests (RF) were employed for full-spectrum classification. Three types of kernels, including linear kernel, polynomial kernel and radial basis function kernel (RBF), were checked for optimization of LS-SVM model. For comparison, a linear discriminant analysis (LDA) model was performed for classification, and the successive projections algorithm (SPA) was executed prior to building an LDA model to choose an appropriate subset of wavelengths. The three methods were applied to a dataset containing 40 raw herbs and 40 corresponding processed herbs. We ran 50 runs of 10-fold cross validation to evaluate the model's efficiency. The performance of the LS-SVM with RBF kernel (RBF LS-SVM) was better than the other two kernels. The RF, RBF LS-SVM and SPA-LDA successfully classified all test samples. The mean error rates for the 50 runs of 10-fold cross validation were 1.35% for RBF LS-SVM, 2.87% for RF, and 2.50% for SPA-LDA. The best classification results were obtained by using LS-SVM with RBF kernel, while RF was fast in the training and making predictions.

Transoral carbon dioxide laser surgery for treatment of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility and curative effects of transoral CO2 laser in treatment of hypopharyngeal carcinoma.</p><p><b>METHODS</b>The retrospective analysis included 24 cases of hypopharyngeal carcinoma from 1994 to 2005 in the Department of Head and Neck. All cases were treated with endoscopic laser surgery and adjuvant selective neck dissection or radiotherapy. The follow-up period was more than 3 years. Twenty-four patients (21 male, 3 female) were classified as follows: 14 cases were T1N0M0, 4 were T1N1M0, 1 was T1N2bM0, 3 were T2N0M0 and 2 were T2N2bM0.</p><p><b>RESULTS</b>Kaplan-Meier survival analysis showed the overall 5-year survival rate was 74.9%, and the 5-year survival rate of T1 lesions and T2 lesions was 78.8% and 60.1%, respectively. The overall 5-year local control rate was 82.1% and 5-year larynx preservation rate was 87.0%. Six of 7 patients with local-regional recurrences underwent salvage surgery and radiotherapy. Finally 4 of them died of recurrence again and 2 were survival. The other one of 7 patients had distant metastasis, and died after radiochemotherapy. One patient died of non-neoplastic diseases. Two patients experienced minor complications with conventional ambulatory treatment without sequelae. All survival patients had laryngeal preservation except the one who received salvage surgery of the hypopharynx and larynx.</p><p><b>CONCLUSIONS</b>Endoscopic CO2 laser surgery with adjuvant selective or modified radical neck dissection and radiotherapy is an alternative for the treatment of selected hypopharyngeal carcinoma, associated with satisfying curative effects and a high larynx preservation rate.</p>