Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

韦氏三联九针法的解读和研究现状

韦氏三联九针是“燕京韦氏眼科学术流派”工作室团队治疗多种眼病，尤其是视神经视网膜退行性疾病的重要针灸处方，临床实践显示疗效较好。笔者对韦氏三联九针法的起源、选穴配穴思路，三联不同部位的针刺手法操作要领进行了解读，并对近年来的研究进展进行了详细阐述。提出在遵循针灸理论基础上，传承并发展的三联九针法，可较大程度提高针灸治疗眼病的疗效。     

欧前胡素抗肿瘤作用机制及治疗的研究进展

欧前胡素是从中药当归中提取的呋喃香豆素类化合物,临床上常用于治疗头痛、炎症、心血管疾病等。近年来研究发现,欧前胡素对多种类型的肿瘤细胞增殖均有抑制作用,能发挥抗肿瘤的功效。本文就欧前胡素对肿瘤及相关疾病的治疗作用和机制进行探讨,以期从不同的角度为肿瘤治疗提供新思路、新方法,并对欧前胡素的进一步研究和开发利用提供理论基础。     

Identification and Validation of Six Autophagy-related Long Non-coding RNAs as Prognostic Signature in Colorectal Cancer

Colorectal cancer (CRC) is a commonly occurring tumour with poor prognosis. Autophagy-related long non-coding RNAs (lncRNAs) have received much attention as biomarkers for cancer prognosis and diagnosis. However, few studies have focused on their prognostic predictive value specifically in CRC. This research aimed to construct a robust autophagy-related lncRNA prognostic signature for CRC. Autophagy-related lncRNAs from The Cancer Genome Atlas database were screened using univariate Cox, LASSO, and multivariate Cox regression analyses, and the resulting key lncRNAs were used to establish a prognostic risk score model. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression of several lncRNAs in cancer tissues from CRC patients and in normal tissues adjacent to the cancer tissues. A prognostic signature comprising lncRNAs {"type":"entrez-nucleotide","attrs":{"text":"AC125603.2","term_id":"21630347","term_text":"AC125603.2"}}AC125603.2, LINC00909, {"type":"entrez-nucleotide","attrs":{"text":"AC016876.1","term_id":"6539320","term_text":"AC016876.1"}}AC016876.1, MIR210HG, AC009237.14, and LINC01063 was identified in patients with CRC. A graphical nomogram based on the autophagy-related lncRNA signature was developed to predict CRC patients'' 1-, 3-, and 5-year survival. Overall survival in patients with low risk scores was significantly better than in those with high risk scores (P < 0.0001); a similar result was obtained in an internal validation sample. The nomogram was shown to be suitable for clinical use and gave correct predictions. The 1- and 3-year values of the area under the receiver operating characteristic curve were 0.797 and 0.771 in the model sample, and 0.656 and 0.642 in the internal validation sample, respectively. The C-index values for the verification samples and training samples were 0.756 (95% CI = 0.668-0.762) and 0.715 (95% CI = 0.683-0.829), respectively. Gene set enrichment analysis showed that the six autophagy-related lncRNAs were greatly enriched in CRC-related signalling pathways, including p53 and VEGF signalling. The qRT-PCR results showed that the expression of lncRNAs in CRC was higher than that in adjacent tissues, consistent with the expression trends of lncRNAs in the CRC data set. In summary, we established a signature of six autophagy-related lncRNAs that could effectively guide clinical prediction of prognosis in patients with CRC. This lncRNA signature has significant clinical implications for improving the prediction of outcomes and, with further prospective validation, could be used to guide tailored therapy for CRC patients.     

江苏省曼氏迭宫绦虫宿主感染调查

目的　了解江苏省曼氏迭宫绦虫宿主感染情况，为曼氏裂头蚴病防控提供科学依据。方法　2018—2019年在江苏省随机抽取9个县（市、区）作为调查点。各调查点随机抽取100名常规健康体检者作为调查对象，进行曼氏迭宫绦虫血清学及病原学检查；在野外环境中调查猫、犬等终宿主及剑水蚤等中间宿主曼氏迭宫绦虫感染情况。结果　江苏省9个调查点人群曼氏迭宫绦虫感染率均为0（0/900），血清抗曼氏裂头蚴IgG抗体阳性率为1.22%（11/900）；中间宿主剑水蚤原尾蚴阳性率为0.33%（3/900），猫、犬等终宿主粪检曼氏迭宫绦虫虫卵阳性率为1.48%（2/135）。结论　江苏省自然环境中存在曼氏迭宫绦虫感染，应加强曼氏裂头蚴病危害和感染途径的健康教育。