特色针灸临床教学分层培养的构建与探索

践行广州中医药大学“重经典、强临床”的高素质中医人才培养模式，秉承“以学生为中心，建立临床思维，提高临床能力，基于不同层级学生精准施教”的教学理念，针对本科生、硕士研究生、博士研究生3 种不同层次的学生开展特色针灸临床教学分层培养。通过深化教学方法改革，建设多元化分层培养教学资源，构建特色针灸临床教学分层培养的教学模式。     

利用Tox21通路数据库评估石家庄市大气细颗粒物中多环芳烃激活毒性通路的风险

目的： 采用Tox21毒性检测数据库中通路数据对2017年石家庄市供暖期大气细颗粒物（PM_2.5）中多环芳烃（PAHs）的检测数据进行分析计算，评估PM_2.5引起毒性通路激活的风险。方法： 在石家庄市河北医科大学远离工业污染源设置1个采样点收集大气PM_2.5，通过气相色谱-串联质谱法（GC-MS）检测美国环境保护署优先控制的16种PAHs的浓度。利用MPPD软件计算各PAHs单体在成人肺泡中的沉积量；检索Tox21毒性检测数据库中芳烃受体（AhR）、核因子E2相关因子（Nrf2）、p53和核因子κB（NF-κB）各通路的剂量反应关系数据，计算各PAHs单体激活各通路的单位强度；结合PAHs在肺泡的沉积量和PAHs激活通路的强度，评估PM_2.5激活各个通路的风险。结果： 石家庄市供暖期PM_2.5中PAHs检测结果显示，苯并[a]芘的日均浓度为9.13 ng/m³，日均浓度排名前3的苯并[b]荧蒽、荧蒽和芘的浓度分别为22.88、17.86及14.31 ng/m³。这16种PAHs以苯并[a]芘为参照的毒性当量浓度为17.74 ng/m³。毒性通路激活风险预测结果提示激活强度最大的是NF-κB通路，其次是AhR、Nrf2，p53被激活的可能性最弱，其中相对应的活性暴露比（AER）值分别为1.97、1.71、0.58和0.28。结论： 石家庄市大气细颗粒物中PAHs的暴露，可能通过激活NF-κB和AhR信号通路增加致癌风险。     

Epidermal growth factor‐induced COX‐2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of angiopoietin‐like 4

Epidermal growth factor receptor (EGFR) expression and activation are the major causes of metastasis in cancers such as head and neck squamous cell carcinoma (HNSCC). However, the reciprocal effect of EGF‐induced COX‐2 and angiopoietin‐like 4 (ANGPTL4) on HNSCC metastasis remains unclear. In this study, we revealed that the expression of ANGPTL4 is essential for COX‐2‐derived prostaglandin E₂ (PGE₂)‐induced tumor cell metastasis. We showed that EGF‐induced ANGPTL4 expression was dramatically inhibited with the depletion and inactivation of COX‐2 by knockdown of COX‐2 and celecoxib treatment, respectively. Prostaglandin E₂ induced ANGPTL4 expression in a time‐ and dose‐dependent manners in various HNSCC cell lines through the ERK pathway. In addition, the depletion of ANGPTL4 and MMP1 significantly impeded the PGE₂‐induced transendothelial invasion ability of HNSCC cells and the binding of tumor cells to endothelial cells. The induction of molecules involved in the regulation of epithelial‐mesenchymal transition was also dependent on ANGPTL4 expression in PGE₂‐treated cells. The depletion of ANGPTL4 further blocked PGE₂‐primed tumor cell metastatic seeding of lungs. These results indicate that the EGF‐activated PGE₂/ANGPTL4 axis enhanced HNSCC metastasis. The concurrent expression of COX‐2 and ANGPTL4 in HNSCC tumor specimens provides insight into potential therapeutic targets for the treatment of EGFR‐associated HNSCC metastasis.     

360度评价在住培学员岗位胜任力评价中的应用

目的运用360度评价对我院住培学员的岗位胜任力进行评价,对学员岗位胜任力的现状进行探讨分析。方法使用问卷调查表分别从专业基地教学主任、学员指导教师、同专业学员及学员本人的角度,对2017级222名住培学员的岗位胜任力进行360度评价,利用SPSS22.0对数据进行统计分析。结果连续两年的测评,住院学员8类岗位胜任力的自评和他评得分低于满分,学员在临床基本能力、医患沟通能力、掌握与运用医学知识、团队合作能力4项内容的评分,差异有统计学意义(P<0.05);同时学员在临床基本能力、医生职业精神与素质、医患沟通能力、掌握与运用医学知识、团队合作能力5项内容的评分较上一年相比,差异也有统计学意义(P<0.05)。结论调查结果提示360度评价可帮助住培学员提高岗位胜任力,后续培训应围绕调查结果和以岗位胜任力为导向来调整与设置,需增加人文属性内容的培训以及再量化培训测评内容、指标和进一步完善考评反馈机制。     

A novel lncRNA-LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.     

急诊科急性心肌梗死患者抢救中优化急诊护理流程应用效果分析

目的:研讨急性心肌梗死患者行优化急诊护理流程的临床效果。方法:摘取单县中医医院2017年8月-2018年11月接收的110例急性心肌梗死患者资料,55例行优化急诊护理流程(研究组),55例行常规护理流程(对照组),比对两组临床指标与心理状态。结果:研究组接诊、术后转运、抢救准备及分诊台停留所用的时间(8.30±2.01)min、(14.67±2.53)min、(7.43±1.19)min、(2.01±0.44)min比对照组短,且抑郁自评量表(Self-rating Depression Scale,SDS)与焦虑自评量表(Self-Rating Anxiety Scale,SAS)评分(40.03±2.36)分、(41.75±1.18)分比对照组低(P<0.05),差异有统计学意义。结论:在抢救中给予急性心肌梗死患者优化急诊护理流程能改善其负面情绪,缩短接诊、术后转运、抢救准备等所用的时间。     

Hepatitis B virus infection and the risk of cancer among the Chinese population

The relationship between hepatitis B virus (HBV) and nonhepatocellular cancers remains inconclusive. This large case-control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (n = 50 392) and controls (n = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression by adjusting age and gender. A meta-analysis based on published studies was also performed to verify the associations. Of these, 12.1% of cases and 5.5% of controls were hepatitis B surface antigen (HBsAg) seropositive. We observed significant associations between HBsAg seropositivity and esophagus cancer (aOR [95% CI] = 1.32 [1.13-1.54]), stomach cancer (1.46 [1.30-1.65]), hepatocellular carcinoma (HCC; 39.11 [35.08-43.59]), intrahepatic and extrahepatic bile duct carcinoma (ICC and ECC; 3.83 [2.58-5.67] and 1.72 [1.28-2.31]), pancreatic cancer (PaC; 1.37 [1.13-1.65]), non-Hodgkin lymphoma (NHL; 1.88 [1.61-2.20]) and leukemia (11.48 [4.05-32.56]). Additionally, compared to participants with HBsAg−/anti-HBs−/anti-HBc−, participants with HBsAg−/anti-HBs−/anti-HBc+, indicating past HBV-infected, had an increased risk of esophagus cancer (aOR [95% CI] = 1.46 [1.24-1.73]), stomach cancer (1.20 [1.04-1.39]), HCC (4.80 [3.95-5.84]) and leukemia (15.62 [2.05-119.17]). Then the overall meta-analysis also verified that HBsAg seropositivity was significantly associated with stomach cancer (OR [95% CI] = 1.23 [1.14-1.33]), ICC (4.05 [2.78-5.90]), ECC (1.73 [1.30-2.30]), PaC (1.26 [1.09-1.46]), NHL (1.95 [1.55-2.44]) and leukemia (1.54 [1.26-1.88]). In conclusion, both our case-control study and meta-analysis confirmed the significant association of HBsAg seropositivity with stomach cancer, ICC, ECC, PaC, NHL and leukemia. Of note, our findings also suggested that the risk of stomach cancer elevated for people whoever exposed to HBV.     

化浊解毒理论治疗糖尿病组方用药规律分析

目的基于中医传承辅助平台软件分析运用化浊解毒理论治疗糖尿病中药处方的用药规律。方法在中国知网(CNKI)、万方和维普数据库检索运用化浊解毒理论治疗糖尿病中药处方,检索词为"化浊解毒"和"糖尿病",检索时间为收录起始年至2018年11月23日。采用关联规则、复杂系统熵聚类等数据挖掘方法,分析处方中药物的使用频次和关联规则,挖掘核心药物组成和新处方。结果共检出226条符合标准的处方,确定黄连、佩兰为高频使用药物;频次24次以上的药物组合19对,其中前3位分别为黄连+佩兰(64次),佩兰+苍术(33次),玄参+佩兰(32次);挖掘出14个核心组合和7首新处方。结论应用化浊解毒理论治疗糖尿病时,药物以清热药、化湿药为主,活血药、淡渗利湿药、补气药、理气药为辅,其中以黄连、佩兰为主,治法主要以化浊解毒为主,淡渗利湿和活血化瘀为辅,兼顾调达气机。     

Melatonin safeguards against fatty liver by antagonizing TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner

Melatonin has been previously shown to prevent nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms are poorly understood. Here, we identified a previously unknown regulatory action of melatonin on apoptosis signal‐regulating kinase 1 (ASK1) signaling pathway in the pathogenesis and development of NAFLD. Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high‐fat diet (HFD)‐induced NAFLD mouse model (in vivo). The protection of melatonin against NAFLD was not affected by inactivation of Kupffer cell in this model. In NAFLD mice liver, ASK1 signal cascade was substantially activated, evidence by the enhancement of total ASK1, phospho‐ASK1, phospho‐MKK3/6, phospho‐p38, phospho‐MKK4/7, and phospho‐JNK. Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK. Mechanistically, we found that lipid stress triggered the interaction between ASK1 and TNF receptor‐associated factors (TRAFs), including TRAF1, TRAF2, and TRAF6, which resulted in ASK1 deubiquitination and thereby increased ASK1 protein stability. Melatonin did not alter ASK1 mRNA level; however, it activated a scaffold protein β‐arrestin‐1 and enabled it to bind to ASK1, which antagonized the TRAFs‐mediated ASK1 deubiquitination, and thus reduced ASK1 protein stability. Consistent with these findings, knockout of β‐arrestin‐1 in mice partly abolished the protection of melatonin against NAFLD. Taken together, our results for the first time demonstrate that melatonin safeguards against NAFLD by eliminating ASK1 activation via inhibiting TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner.     

Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori

Isopentenylation at A37 (i⁶A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1–BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock‐down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i⁶A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.