法医毒物分析实验教学多元化模式改革

法医毒物分析是法医学专业的主干课程之一,实践性强,应注重培养学生敏锐观察能力、实践探索能力及综合运用能力。在法医毒物分析实验教学中,引入仿真的案件现场、开放的实验平台和实验教具,营造一个立体化法医毒物分析实验教学模式,从而加深学生对毒物的认识,激发学生对案件的思考,完成理论知识到实践的转化。     

一例肿瘤合并2019冠状病毒病(COVID-19)患者的治疗决策分析

目的: 探讨亟待进行肿瘤根治术的患者合并2019冠状病毒病（COVID-19）后如何选择手术治疗时机。方法: 详细分析1例乙状结肠癌合并COVID-19患者的治疗过程,以及该患者在病毒两次转阴后进行根治性手术后的恢复情况。结果: 患者术后恢复良好,炎症指标、发热等临床表现改善,肺部病灶也维持稳定。结论: 对于亟待进行肿瘤根治术且合并COVID-19的患者,在符合病毒核酸检测两次阴性之后进行肿瘤根治术是可行的。     

药用辅料红糖的全波长融合指纹图谱研究

目的 研究并建立药用辅料红糖的紫外全波长融合指纹图谱。方法 采用Durashell C₁₈-AM色谱柱（4.6 mm×250 mm,5 μm,100 A）,乙腈-0.1%三氟乙酸水作流动相,流速1.0 mL/min,梯度洗脱,柱温25 ℃,采用PDA检测器进行210~400 nm全波长检测,使用Waters Empower 3色谱数据软件对210~400 nm紫外全波长数据进行融合,使用中药色谱指纹图谱相似度评价系统软件进行相似度分析。结果 35批药用辅料红糖的紫外全波长融合指纹图谱经相似度分析后共标出10个共有色谱峰,各批次的指纹图谱相似度均大于0.9,相似度良好。结论 该方法稳定准确,重复性好,可以为制定药用辅料红糖指纹图谱的质量标准提供依据。      

基于UPLC-Q-TOF-MS技术分析痤疮消洗液化学成分

目的 定性分析治疗痤疮的临床验方痤疮消洗液中的化学成分。方法 采用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）技术,选用Acquity HSS T₃色谱柱（2.1 mm×100 mm,1.8 μm）,0.1%甲酸乙腈和0.1%甲酸水为流动相进行梯度洗脱,流速为0.3 mL/min,质谱使用ESI离子源,正负离子模式扫描采集数据。通过精确质谱信息及元素组成分析,结合Scifinder数据库、对照品信息及相关文献,对痤疮消洗液中的化学成分进行推断和鉴定。结果 痤疮消洗液中鉴定出59个化合物,它们分别为蒽醌类、环烯醚萜类、有机酸类、黄酮类化合物。结论 UPLC-Q-TOF-MS技术可快速、灵敏地鉴定痤疮消洗液中的化学成分,为探讨药效物质基础及控制制剂质量提供了实验依据。      

HAART患者失访相关影响因素Logistic回归分析

目的 探讨艾滋病抗病毒治疗患者失访发生的相关影响因素,为HIV/AIDS患者管理提供依据。方法 收集2005年6月-2018年12月在南宁市第四人民医院进行抗病毒治疗的艾滋病抗病毒治疗患者为研究对象,使用Excel的RAND随机函数生成的随机数字由小到大进行排序,选取排序前200例的HAART失访的患者为观察组,对照组为在治疗的艾滋病患者中随机选取的200例。采用Logistic回归分析方法分析患者性别、年龄、基线CD4⁺T淋巴细胞计数、传播途径、基线疾病分期、目前疾病分期、最近1次CD4⁺T淋巴细胞计数、领药、婚姻状况、子女人数、地区、药物不良反应等12项因素与失访的关系。结果 观察组接受HAART 12个月内失访85例,占总失访人数的42.5%,24个月内失访123例,占总失访人数的61.5%。将12个因素进行多因素logistic回归分析,最终进入回归模型的因素为传播途径、最近1次CD4⁺T淋巴细胞、药物不良反应,其调整的OR值及OR95%CI分别为6.26(2.99~13.10)、8.68(4.32~17.45)、10.52(2.77~40.00)。结论 HIV/AIDS患者HAART 失访大部分发生在开始治疗的2年内,对出现HAART有不良反应的患者进行及时处理或更换治疗方案,强化对注射吸毒、治疗后CD4⁺T淋巴细胞提升不理想HIV/AIDS感染者的个体指导和警示教育,增强患者治疗信心,减少失访的发生。     

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure

Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four groups(25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 m W/cm^2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram(EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor(NMDAR) subunits(NR1, NR2 A, and NR2 B), c AMP responsive element-binding protein(CREB) and phosphorylated CREB(p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. Results The rats in the 10 and 30 m W/cm^2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 m W/cm^2 group had increased expressions of NR2 A and NR2 B and decreased levels of CREB and p-CREB. Conclusion Shortwave exposure(27 MHz, with an average power density of 10 and 30 m W/cm^2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.     

Persistently Upregulated Hippocampal mTOR Signals Mediated by Fecal SCFAs Impair Memory in Male Pups with SMM Exposure in Utero

Objective To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin(SMM) in pregnancy on the neurobehavioral development of male offspring. Methods Pregnant mice were randomly divided into four groups: control‐(normal saline), low‐[10 mg/(kg.day)], middle‐[50 mg/(kg.day)], and high‐dose [200 mg/(kg.day)] groups, which received SMM by gavage daily during gestational days 1‐18. We measured the levels of short‐chain fatty acids(SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mR NA and protein levels of genes involved in the mammalian target of rapamycin(m TOR) pathway in the hippocampus of male pups by RT‐PCR or Western blotting. Results Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day(PND) 22 and 56. Furthermore, the phosphatidylinositol 3‐kinase(PI3 k)/protein kinase B(AKT)/mTOR or mT OR/ribosomal protein S6 kinase 1(S6 K1)/4 EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase(SPR), a potential target of m TOR, was inhibited. Conclusion In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut(SCFA)‐brain axis may contribute to cognitive deficits in male offspring.     

Next-generation Sequencing Study of Pathogens in Serum from Patients with Febrile Jaundice in Sierra Leone

Objective People in Western Africa suffer greatly from febrile jaundice, which is caused by a variety of pathogens. However, yellow fever virus(YFV) is the only pathogen under surveillance in Sierra Leone owing to the undeveloped medical and public health system there. Most of the results of YFV identification are negative. Elucidation of the pathogen spectrum is required to reduce the prevalence of febrile jaundice. Methods In the present study, we used Ion Torrent semiconductor sequencing to profile the pathogen spectrum in archived YFV‐negative sera from 96 patients in Sierra Leone who presented with unexplained febrile jaundice. Results The most frequently identified sequencing reads belonged to the following pathogens: cytomegalovirus(89.58%), Epstein‐Barr virus(55.21%), hepatitis C virus(34.38%), rhinovirus(28.13%), hepatitis A virus(20.83%), coxsackievirus(10.42%), Ebola virus(8.33%), hepatitis E virus(8.33%), lyssavirus(4.17%), leptospirosis(4.17%), chikungunya virus(2.08%), Crimean‐Congo hemorrhagic fever virus(1.04%), and hepatitis B virus(1.04%). Conclusion The distribution of sequencing reads suggests a broader spectrum of pathogens for consideration in clinical diagnostics and epidemiological surveillance in Sierra Leone.     

Th1/Th2细胞因子在眼肌型重症肌无力转基因小鼠模型中的作用机制

目的 观察重组人乙酰胆碱受体(H-AChR) γ亚单位免疫HLA-DQ8转基因小鼠眼肌型实验性自身免疫性重症肌无力(oEAMG)模型体外培养上清液中Th1/Th2细胞因子水平变化,探讨其与oEAMG免疫学发病机制的联系。方法 HLA-DQ8转基因小鼠用乳化于完全弗氏佐剂(CFA)的重组H-AChR γ亚单位,或E. Coli提取物,或纯CFA分别免疫,分别于第0天、第30天和第60天共免疫3次。第3次免疫后28 d,处死小鼠后取淋巴结和脾淋巴细胞体外培养,收集培养上清液,采用ELISA法检测白细胞介素(IL)-2、γ-干扰素(IFN-γ)、IL-6和IL-10水平。结果 H-AChR γ组小鼠淋巴结及脾淋巴细胞体外培养上清液中IL-2(F=42.835,P<0.001;F=38.030,P<0.001)和INF-γ水平(F=76.332,P<0.001;F=34.865,P<0.001)均明显高于E. coli组和CFA免疫组;IL-6(F=1.325,P=0.284;F=1.935,P=0.166)和IL-10水平(F=0.908,P=0.417;F=1.189,P=0.322)与E. coli 组和CFA组差异无统计学意义。结论 Th1细胞因子在重组H-AChR γ亚单位诱导HLA-DQ8转基因小鼠所建立oEAMG模型的发病机制中可能发挥重要作用,而Th2细胞及其细胞因子作用尚不十分明确。