浅论中医学对胰腺实体解剖的认知过程

中医学古籍中罕有关于“胰腺”的明确记载，缺乏直观、系统的理论论述。本文试图通过对各个时期具有代表性的医学典籍所记载内容的分析，结合现代解剖学相关理论，梳理中医学对胰腺实体解剖的认识过程。通过分析，笔者认为中医学对胰腺实体解剖的认识具有阶段性：①先秦两汉时期，存在胰腺实体解剖，但并非认为胰腺是脏器；②唐宋时期，胰腺实体解剖更加清晰，在医学上胰腺附属于脾，并非为独立的脏器；③明清时期，胰腺实体解剖明确，部分医家以独立脏器论之，出现“脾”、“胰”之争。中医学理论缺少对胰腺的单独论述，目前学界的主流观点多为“胰属脾”，线性归属以脾笼统代之略显单薄，不利于理论的丰富与发展。笔者认为胰腺藏象应独立于脾单独讨论，现代解剖学对胰腺命名同一，形态结构清楚，位置描述明确，可直接补充进中医学胰腺藏象（藏）理论中，为完善胰腺藏象理论搭建解剖学基础。     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.     

“三全育人”视角下思政教育机制实践与探索——“杏林成长导师”计划的构建

“三全育人”是高校思政教育工作的关键一环，也是中医药高校推动思政教育的重要内容。以“三全育人”为视角对北京中医药大学思想政治教育举措“杏林成长导师”计划路径、内容深入分析，运用统计分析和文献研究方法，剖析该计划对中医学专业大学生的学业、思想和实践等多个层面的现实成效，从而为“三全育人”理念在中医药院校制度建构中的应用提供新的视角与方法。     

Clinical Effectiveness of Erlova in EGFR-Mutated Non-Small Cell Lung Cancer: An Affordable Price with Clinical Benefit

Background: Thyrosin kinase inhibitors (TKIs) is approved for the first line treatment of non-small cell lung cancer (NSCLC) patients with  epidermal growth factor receptor (EGFR) mutation. This study performed to assess clinical effectiveness and safety of Erlova (generic form of Erlotinib). Methods: Somatic mutations of EGFR gene were studied in tumor tissue by polymerase chain reaction (PCR) and bi-directional sequencing in 513 chemonaive and histologically verified lung adenocarcinoma Iranian patients. Patients  with EGFR mutation received Erlova at 150 mg/day  as first line treatment. Primary endpoint was progression free survival (PFS). Results: About 21% (n=109) cases had EGFR mutation. Most EGFR mutations were  occurred at exon 19. Among them, sixty nine patients treated with Erlova. Median PFS was 11.4 months and objective response rate (ORR) was about  88%. Most frequent treatment related adverse events was  skin rash. Conclusion: Our findings showed Erlova had remarkable effectiveness. In  mutation-positive patients with EGFR, Erlova can be used  safely instead of  other tyrosine-kinase inhibitors.     

hsacirc0006867在结直肠癌组织中的表达及其临床意义北大核心

目的:探讨环状RNA hsa_circ_0006867在结直肠癌中的表达及其与临床病理因素的关系。方法:全转录组测序筛选结直肠癌中特异circRNAs表达谱,挑选出差异表达显著的hsa_circ_0006867,qRT-PCR检测54例结直肠癌组织及癌旁组织中hsa_circ_0006867表达情况,分析其表达水平与结直肠癌临床病理特征的相关性,ROC曲线分析hsa_circ_0006867在结直肠癌中的诊断价值。结果:测序获得circRNAs在结直肠癌中的差异表达谱,qRT-PCR验证hsa_circ_0006867在结直肠癌中表达下调(P<0.05)。其表达水平与肿瘤分化程度和远处转移有关(P<0.05)。ROC曲线显示hsa_circ_0006867诊断结直肠癌AUC为0.851(95%CI:0.775~0.927),当截断值为0.0146时,敏感度为88.46%(95%CI:0.770~0.946),特异度为73.08%(95%CI:0.598~0.832),差异具有统计学意义(P<0.001)。结论:hsa_circ_0006867在结直肠癌中表达下调,与相关临床病理特征密切联系,可作为潜在结直肠癌临床诊断指标。     

Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

三阴性乳腺癌治疗的研究进展

三阴性乳腺癌（triple negative breast cancer，TNBC）是雌激素受体(estrogen receptor，ER)、孕激素受体（progesterone receptor，PR）及人类表皮生长因子受体（human epidermal growth factor-2,HER-2）均不表达的乳腺癌。按其功能特征可归纳为5类分子分型:以DNA修复缺陷或生长因子为途径的基底细胞样三阴性乳腺癌；以上皮-间充质转化和肿瘤干细胞为特征的间质样三阴性乳腺癌；免疫调节型三阴性乳腺癌；雄激素受体过表达的管腔／分泌型三阴性乳腺癌；HER-2富集型三阴性乳腺癌。三阴性乳腺癌恶性程度高且异型性较大，其治疗困难且预后较差，内分泌治疗及靶向治疗不敏感。目前很多学者对于三阴性乳腺癌的治疗各有研究，并有临床试验证实下述治疗有效。     

“醒脑开窍”针法配合芒针治疗前列腺增生合并慢性尿潴留

患者男,74岁,主因尿频、尿急、排尿困难10余年,加重1个月,患者因脑梗死后遗症康复治疗于2018年8月1日就诊于天津中医药大学第一附属医院针灸科。查颅脑MR:未见新发梗死灶。患者10余年前发现尿频、尿急、尿不尽、夜尿多等症状,曾诊断“良性前列腺增生”,未经系统诊治。     

Ginsenoside Rg1 prevents acetaminophen-induced oxidative stress and apoptosis via Nrf2/ARE signaling pathway

Inappropriate use of acetaminophen (APAP) can lead to morbidity and mortality secondary to hepatic necrosis. Ginsenoside Rg1 is a major active ingredient in processed Panax ginseng, which is proved to elicit biological effects. We hypothesized the beneficial effect of Rg1 on APAP-mediated hepatotoxicity was through Nrf2/ARE pathway. The study was conducted in cells and mice, comparing the actions of Rg1. Rg1 significantly improved cell survival rates and promoted the expression of antioxidant proteins. Meanwhile, Rg1 reduced the excessive ROS and the occurrence of cell apoptosis, which were related to Nrf2/ARE pathway. Expression of Nrf2 has a certain cell specificity.