Updated developments on molecular imaging and therapeutic strategies directed against necrosis

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.     

川黄方对2～4期慢性肾脏病合并急性肾损伤患者肾功能及氧化应激的影响

目的:观察川黄方对2～4期慢性肾脏病(CKD)合并急性肾损伤(AKI)患者的临床疗效,并从氧化应激角度探讨其疗效机制。方法:纳入84例CKD合并AKI患者,随机分为治疗组42例和对照组42例。所有患者均给予基础治疗(纠正水、电解质、酸碱平衡紊乱,控制血压等),对照组患者在此基础上给予前列腺素E1注射液静脉滴注,治疗组在对照组治疗基础上给予川黄方汤剂口服及浓煎剂灌肠,两组疗程均为2周。评价并比较两组患者的临床疗效及中医证候积分,检测并比较两组患者的血肌酐(Scr)、血尿素氮(BUN)、血尿酸(UA)、24 h尿蛋白定量(24 h U-pro)、估算的肾小球滤过率(eGFR)及血清血红素加氧酶-1(HO-1)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平。结果:①治疗后,治疗组的临床总有效率为71.4%,对照组为45.2%,两组间比较差异有统计学意义(P0.01),治疗组的疗效优于对照组。②治疗后,两组患者的中医证候积分较治疗前均显著降低(P0.01),且治疗组患者的积分下降程度较对照组更明显(P0.05)。③治疗后,两组患者的Scr、BUN、UA水平较治疗前均明显降低(P0.05,P0.01),eGFR水平较治疗前显著升高(P0.05,P0.01),且治疗组患者的Scr、BUN水平降低程度及eGFR水平升高程度较对照组更明显(P0.05,P0.01);两组患者的24 h U-pro较治疗前均降低(P0.05),且治疗组患者的24 h U-pro降低程度较对照组更明显(P0.05)。④治疗后,两组患者的血清HO-1、SOD水平较治疗前显著升高(P0.05),MDA水平较治疗前显著降低(P0.05,P0.01),且治疗组患者的HO-1、SOD水平升高程度及MDA水平降低程度较对照组更明显(P0.05)。结论:川黄方能有效减轻CKD合并AKI患者的肾损伤、保护肾功能,改善患者的中医证候,其机制可能与抑制氧化应激有关。     

信息化物品管理系统的应用效果分析

目的利用信息化物品管理系统提高医院管理水平,保证护理工作安全。方法在移动护理工作站、医院信息系统和无线网络等设施的基础上,建立信息化物品管理系统。分析应用信息化物品管理系统的临床效果,比较物品交接时间,药品丢失数量及护士工作满意度情况。结果与传统护理物品管理方式相比,使用信息化物品管理系统进行物品交接的平均用时显著降低(t=10.66,P<0.001),药品丢失数量明显减少(χ2=4.215,P=0.040),体温计丢失数量明显减小(χ2=4.643,P=0.031),护士工作满意度明显提高(χ2=5.699,P=0.017)。结论信息化物品管理系统使物品管理更规范、更准确、更科学,提高护士工作效率,改进护理工作质量,保障医疗安全。     

结直肠癌组织浸润免疫细胞组成及特征

目的：研究结直肠癌（CRC）患者和健康人大肠组织中免疫细胞的浸润情况,为后续开展肿瘤微环境的研究提供前期的分析结果和数据。方法：通过GEO数据库对51例正常人结直肠组织和333例CRC患者肿瘤组织的基因表达谱数据进行计算分析,通过CIBERSORT方法将基因表达谱数据转化为组织中22种免疫细胞的浸润比例,对比这些免疫细胞在两者中的分布情况。结果：肠道浸润的免疫细胞组成在CRC患者与健康人之间有较大差异。T细胞和B细胞在肿瘤组织中的浸润数量少于健康人,而巨噬细胞、中性粒细胞、肥大细胞和树突状细胞在肿瘤组织中的浸润数量大于健康人。结论：CRC患者和健康人的结直肠组织中免疫细胞浸润存在较大的差异,这些具有差异的免疫细胞在癌症进展中可能发挥重要作用。     

The structural composition of components contributes to the superiority of the geoherb Alisma orientale for “diuresis and diffusing dampness”

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale. The effects of “diuresis and diffusing dampness” using salt-made Alisma orientale from seven different origins were investigated through pharmacodynamic experiments in vivo and in vitro. The results indicated that salt-made Alisma orientale from different origins had diuretic efficacy; this was demonstrated by the significant increase in the volume of rat urine, the concentration of Na⁺, K⁺, and Cl⁻ in the urine, and the significant decrease in the levels of AQP-2 in rat renal medulla and HK-2 cells. It was also revealed that the diuretic effect of salt-made Alisma orientale from Fujian Province is stronger than those from other provinces. Moreover, the main components and their proportions in the salt-made Alisma orientale samples were further analyzed via principal component analysis. The results showed that alisol A 24-acetate, alisol B, and 23-acetyl alisol B are the main components of salt-made Alisma orientale, and the optimal structural ratio of alisol A 24-acetate, alisol B, and 23-acetyl alisol B was found to be 5.38 : 14.34 : 11.31 via optimizing the ratios of the three main components. It is worth noting that the optimal ratio of the three main components after optimization is the closest to the ratio of the three main components in salt-made Alisma orientale from Fujian Province. This paper reveals the “mystery” of the content ratio of the main active components and its effect on the efficacy, and showed that the proportional relationship between the content of multiple components is the key to their interactions. Therefore, this method of evaluating the quality of salt-made Alisma orientale is obviously reliable, and this study lays the foundations for quality evaluation of salt-made Alisma orientale and other herb slices.

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale.     

粪便内中短链脂肪酸柱前衍生化UHPLC-QTOF-MS/MS分析方法研究

建立柱前衍生化超高效液相色谱-串联四级杆飞行时间质谱(UHPLC-QTOF-MS/MS)定性、定量表征小鼠粪便内中短链脂肪酸的方法,并用于评价其在抗生素处置前后小鼠粪便样品中的变化。动物实验方案获得江苏省中医药研究院动物实验伦理委员会的批准。以3-硝基苯肼为衍生化试剂,对衍生化反应条件、色谱及质谱条件进行优化,建立了粪便中16个中短链脂肪酸的定性、定量方法。所有分析物在各自浓度范围内线性关系良好(R2>0.99),日内、日间精密度RSD均小于10%,重复性RSD小于6%,加样回收率介于80%~120%之间,样品36 h内稳定性RSD小于7%;联合抗生素处置后小鼠粪便内的中短链脂肪酸种类和含量均发生了明显改变。其中,甲酸、乙酸、丙酸、丁酸、异丁酸、戊酸、乳酸等含量明显降低,而庚酸和丁二酸的含量明显增加。该方法准确、可靠,可作为粪便内中短链脂肪酸的表征方法。     

~(60)Co-γ辐照前后姜黄HPLC指纹图谱和姜黄素含量变化研究

目的测定姜黄饮片中姜黄素的含量,并建立姜黄的HPLC指纹图谱,评价~(60)Co-γ辐照对姜黄化学成分的影响。方法对~(60)Co-γ辐照前后13批次姜黄饮片粉末中姜黄素含量进行测定;建立姜黄饮片HPLC指纹图谱并对其方法学进行考察。采用配对样本t检验和中药色谱指纹图谱相似度评价软件对辐照前后姜黄化学成分变化进行分析,结合聚类分析(HCA)和主成分分析(PCA)对辐照前、后样品进行综合评价,并对3批次姜黄样品辐照后3、6个月的稳定性进行了考察。结果 13批次姜黄粉末辐照前后姜黄素含量无统计学差异(P0.05);姜黄HPLC指纹图谱确定了16个共有峰,各批次姜黄辐照前后指纹图谱的相似度均大于0.998;同批次辐照前与辐照后样品聚类一致性较好,3批次辐照前后姜黄样品放置3、6个月后与0个月相比姜黄素含量变化RSD5%,指纹图谱相似度均大于0.95。结论 ~(60)Co-γ辐照对姜黄中姜黄素含量和整体化学成分一致性基本无影响,且不影响其稳定性,通过指纹图谱结合指标成分含量分析可以更好地评价~(60)Co-γ辐照对姜黄化学成分的影响,为姜黄辐照灭菌方式的选择提供了实验依据。     

重楼提取物抗骨肉瘤作用及机制研究

目的探讨重楼提取物(PPEE)抗骨肉瘤作用及其机制。方法不同质量浓度的PPEE处理骨肉瘤细胞,采用MTT法、Hoechst 33342染色、流式细胞术、Matrigel培养、免疫印迹法分别检测细胞增殖抑制率、细胞凋亡、细胞周期、血管生成拟态(VM)形成及相关蛋白表达情况。裸鼠移植瘤模型观察PPEE的体内抑瘤效果。结果 PPEE对骨肉瘤细胞半数抑制浓度(IC50)为10～60μg/m L,对成骨细胞增殖影响较小。PPEE可浓度依赖性地将骨肉瘤143B细胞阻滞在G2/M期,上调细胞周期相关蛋白p-CDK1、p-Cdc25C、p-Chk2表达,下调cyclinB1表达;促进细胞凋亡,上调cleavedCaspase-3、8、9和PARP表达,上调Bax/Bcl-2;抑制细胞体外VM形成,下调FAK、Mig-7、MMP-2和MMP-9表达。体内实验显示PPEE能明显抑制骨肉瘤生长和体内VM形成,延长荷瘤裸鼠生存期。结论 PPEE在体内外均具有良好的抗骨肉瘤活性,其作用机制可能与诱导骨肉瘤细胞凋亡、阻滞细胞周期及破坏骨肉瘤VM形成有关。     

交联纳米SiO_2固定化蜗牛酶的制备表征及转化淫羊藿苷研究

目的制备交联纳米Si O2固定化蜗牛酶,并对其理化性质、酶解淫羊藿苷为宝藿苷I的最适酶解条件及酶学性能进行考察。方法采用共价偶联法将蜗牛酶固定在戊二醛交联纳米Si O2上,以相对酶活力为指标,对固定化条件进行优化;采用透射电镜(TEM)、傅里叶红外光谱(FTIR)和元素分析法对固定化蜗牛酶的理化性质进行表征;并以淫羊藿苷为底物,以游离酶为对照,考察固定化蜗牛酶的最适酶解条件及酶解动力学参数、重复利用性、热稳定性等酶学性能。结果固定化蜗牛酶制备的最佳酶载比为1∶3,固定化时间为6 h;其转化淫羊藿苷的最适酶解条件为pH 5.0,转化温度60℃,酶与底物质量比1∶2,转化时间12 h。固定化蜗牛酶的酶解动力学参数最大反应速率(Vmax)为0.43μg/min,米氏常数(Km)为0.78 mmol/L,重复使用5次后的相对酶活仍能保持在70%以上。结论制备的交联纳米Si O2固定化蜗牛酶机械强度高、稳定性好,不但可重复使用,还可定向水解淫羊藿苷为活性更强的宝藿苷I,工艺简单易行,转化效率高,适宜于工业化生产。