pH对生物合成超声分子影像探针气囊充放气的调控

气囊（gas vesicles,GVs）是一种存在于蓝藻及古菌等微生物中调节浮力的类细胞器纳米结构,由蛋白质外壳包裹气体组成。近年来的研究表明,气囊具有作为超声分子影像探针的潜力。然而,气囊的充放气机制并不明确,限制了生物合成超声分子影像探针的保存和气体更换。本研究发现环境pH值是调节气囊充放气的一个重要因素。其不仅可以调节藻细胞内的气囊充放气进而使微囊藻呈现不同的漂浮状态,还可对提纯的气囊充放气进行体外调节,且该调节过程可逆。该机制的阐明为生物合成超声分子影像探针的大规模生产和保存,特别对气囊中的气体进行更换以满足不同的诊疗需求提供了技术支持,助力生物合成超声造影剂在疾病诊疗中的应用。     

泌尿系造影联合彩色多普勒对小儿先天性肾积水的诊断价值评估

摘要 目的：探讨泌尿系造影联合彩色多普勒对小儿先天性肾积水的诊断价值。方法：选取2018年11月～2021年11月在本院治疗的88例先天性肾积水患儿为研究对象,所有患儿均完善静脉肾盂造影及彩色多普勒超声检查,以病理诊断结果为金标准,对比两种检查方法对小儿先天性肾积水的诊断价值。结果：彩色多普勒超声检查结果显示,肾积水轻度、中度、重度患儿分别为10例、39例、39例,不同病情程度患儿比较,重度组收缩期峰值速度（PSV）、舒张期最小流速（EDV）均低于中度组和轻度组,重度组血流阻力指数（RI）高于中度组和轻度组（P<0.05）,但轻度组与中度组PSV、EDV、RI比较差异无统计学意义（P>0.05）。与病理学诊断检查结果对比,彩色多普勒超声对中度、重度先天性肾积水患儿具有较高的诊断效能,其准确度分别为90.91%、93.18%,与病理诊断kappa值分别为0.795、0.862,具有较高的一致性;但对轻度肾积水诊断效能较低,kappa值为0.629,一致性一般。静脉肾盂造影对轻度先天性肾积水患儿具有较高的诊断效能,准确度为96.59%,与病理诊断kappa值为0.824,具有较高的一致性;但对中度、重度肾积水诊断效能较低,kappa值分别为0.583、0.565,一致性一般。彩色多普勒超声联合静脉肾盂造影诊断准确率高达94.32%,明显高于两检查方法单独应用（P<0.05）。结论：不同病情程度的先天性肾积水患儿具有不同超声征象,彩色多普勒超声对中、重度肾积水患儿具有较好的诊断价值,而静脉肾盂造影诊断轻度肾积水患儿的效能较好,将二者联合可提高对先天性肾积水的诊断准确率。     

肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例,根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少,差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加,差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高,差异有统计学意义（P＜0.05）。Spearman相关性分析显示,达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）;峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性,两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。     

经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后子宫内膜癌的诊断效能

摘要 目的：探讨经阴道三维超声联合糖类抗原125（CA125）、糖类抗原199（CA199）、中性粒细胞/淋巴细胞比值（NLR）及血小板/淋巴细胞比值（PLR）检测对绝经后女性子宫内膜癌（EC）的诊断效能。方法：回顾性分析本院2019年5月至2022年5月收治的因绝经后出血就诊的92例疑似子宫内膜肿瘤患者的病历资料,经手术病理证实,EC患者48例（EC组）、子宫内膜良性病变患者44例（良性组）。比较两组CA125、CA199、NLR及PLR水平,对比两组子宫内膜血管指数（VI）、血流指数（FI）、血管-血流指数（VFI）、子宫内膜容积（EV）变化及血流信号分布情况。绘制受试者工作特征（ROC）曲线分析经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后EC的诊断效能。结果：EC组CA125、CA199、NLR及PLR水平均高于良性组（P＜0.05）。EC组三维超声参数VI、FI、VFI及EV均高于良性组（P＜0.05）。EC组血流信号Ⅱ级占比25.00%,Ⅲ级占比70.83%;良性组血流信号Ⅱ级占比88.64%,Ⅲ级占比2.27%。EC组血流信号Ⅱ级占比低于良性组,血流信号Ⅲ级占比高于良性组（P＜0.05）。两组血流信号0级、Ⅰ级比较无差异（P＞0.05）。ROC结果显示五项检查联合检测曲线下面积（AUC）值为0.944（95%Cl：0.902~0.985）,具有更优的诊断效能（敏感度为89.10%、特异度为91.80%）。结论：CA125、CA199、NLR及PLR检测联合经阴道三维超声检查诊断绝经后EC效果显著,可为临床诊断提供参考。     

超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值

摘要 目的：探讨超声造影定量分析联合血清甲胎蛋白（AFP）、血管内皮生长因子受体-2（VEGFR-2）、可溶性T细胞免疫球蛋白粘蛋白分子3（sTim-3）对原发性肝癌肝动脉化疗栓塞（TACE）治疗疗效的预测价值。方法：选择2020年1月至2022年10月海军军医大学第二附属医院收治的原发性肝癌患者94例。行TACE治疗2个月,采用改良的实体瘤疗效评价标准评估患者疗效,根据不同疗效分为疗效不良组（n=32）和疗效良好组（n=62）。所有患者均行超声造影检查,比较两组超声造影定量分析参数、治疗前血清AFP、VEGFR-2、sTim-3水平,采用受试者工作特征（ROC）曲线分析超声造影定量分析参数联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值。结果：经TACE治疗,62例患者疗效良好、32例患者疗效不良,治疗有效率为65.96%。疗效良好组术前超声造影达峰时间、等增强开始时间显著长于疗效不良组（P<0.05）。疗效良好组术前血清AFP、VEGFR-2、sTim-3水平显著低于疗效不良组（P<0.05）。ROC曲线分析结果显示,超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效预测的曲线下面积（AUC）为0.950,灵敏度为84.85%,特异度为82.12%,高于各指标单独检测。结论：超声造影定量分析参数、血清AFP、VEGFR-2、sTim-3水平可预测原发性肝癌患者TACE治疗的疗效,且联合诊断的预测效能更高。     

经会阴盆底超声联合血清雌二醇对女性压力性尿失禁的诊断价值研究

摘要 目的：研究经会阴盆底超声联合血清雌二醇对女性压力性尿失禁（SUI）的诊断价值。方法：选取川北医学院附属医院2018年1月～2022年12月收治的女性SUI患者81例,记作观察组。另选取同期体检正常女性80例作为对照组。比较两组盆底超声参数以及血清雌二醇水平。采用受试者工作特征（ROC）曲线分析上述各项指标单独和联合检测的诊断效能。结果：观察组静息状态下近段尿道和人体纵轴间夹角（UIA）、最大Valsalva动作下近段尿道和膀胱后壁的夹角（PUVA）以及尿道旋转角（URA）相较于对照组较高（均P＜0.05）。观察组血清雌二醇水平相较于对照组明显更低（P＜0.05）。经ROC曲线分析发现：各项盆底超声参数联合血清雌二醇诊断女性SUI的效能优于各项指标单独诊断。结论：经会阴盆底超声可诊断女性SUI,在联合血清雌二醇时诊断女性SUI的价值更高。     

EPR Spin Trapping Study of the Decomposition of Azo Compounds in Aqueous Solutions by Ultrasound: Potential for Use as Sonodynamic Sensitizers for Cell Killing

Sonodynamic therapy, a promising new approach to cancer treatment, is based on synergistic cell killing by combination of certain drugs (sonosensitizers) and ultrasound. Although the mechanism of sonodynamic action is not understood, the role of free radicals produced from sonosensitizers by ultrasound is implicated. In this work, we studied formation of free radicals during the decomposition of several water-soluble azo compounds by 50 kHz ultrasound in aqueous solutions. Using the spin trap 3, 5-dibromo-4-nitrosobenzene sulfonate (DBNBS) tertiary carbon-centered radicals from 2, 2'-azobis (N,N'-dimethyl-eneisobutyramidine) dihydrochloride (VA-044), 2-(carbamoylazo)-isobutyronitrile (V-30), and 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and CH3 radicals from 1, 1'-azobis (N,N'-dimethylformamide) (ADMF) were detected in argonsaturated solutions and the corresponding oxygen-centered radicals (alkoxyl and peroxyl) from VA-044, V-30, and AAPH were identified using the spin trap 5, 5'-dimethyl-l-pyrroline-N-oxide (DMPO) in aerated sonicated solutions. No free radicals from 4, 4'-dihydroxyazobenzene-3, 3'-dicarboxylic acid, disodium salt (DHAB) could be found in either system. While VA-044 and AAPH could also be readily decomposed by heat (42.5°C and 80°C), V-30 decomposition only occurred in the ultrasound-exposed solutions. The most likely mechanism of decomposition of azo compounds by ultrasound is their thermolysis in the heated shell of the liquid surrounding ca vita ting bubbles driven by ultrasound and/or by pyrolysis inside these bubbles. Experiments using scavengers of ·OH and ·H, which are produced by sonolysis in aqueous solutions, demonstrated that these radicals are not involved in the ultrasound-mediated radical production from the azo compounds. Due to the known cytotoxic potential of free radicals produced from azo compounds, the use of these compounds as ultrasound sensitizers appears to be a promising approach for sonodynamic cell killing.     

神经生长因子家族及其受体研究进展

过去几年在神经营养因子、受体和神经元细胞程序性死亡的研究领域中取得了几项引人注目的进展：（１）神经生长因子（ＮＧＦ）基因家族的其他一些成员包括脑源性神经营养因子（ＢＤＮＦ）、神经营养素－３（ＮＴ－３）、神经营养素－４（ＮＴ－４）、神经营养素－５（ＮＴ－５）的发现;（２）神经生长因子三维结构及功能和进化之关系的阐明;（３）定性了两种神经生长因子受体Ｐ７５＾ＮＧＦＲ和原癌基因ｐ１４０＾ｔｒｋＡ以及相关     

Sexual differences in the Golgi apparatus of rat hepatocytes: three-dimensional analysis

Lipid metabolism takes place in the Golgi apparatus, but at a higher rate in female than in male rats. I therefore examined the Golgi apparatus by morphometric means for differences between the sexes at the light-and electron-microscopic level. The Golgi apparatus was stained in situ by a zinc-iodide-osmium method. The counts of the Golgi apparatus in cross-sections in female hepatocytes by light microscopy were approximately twice that in male hepatocytes. Upon ovariectomy, these counts were greatly reduced but were reestablished after estrogen supplement. To clarify this phenomenon, three-dimensional reconstructions of the Golgi apparatus were produced from electron-microscopic images of serially cut 160-nm sections. The Golgi apparatus of both male and ovariectomized females had the shape of a small ring, whereas it took the form of a large elongated cylinder in normal females and in castrated males after treatment with estrogen. The numerical difference in Golgi apparatus counts by light microscopy of in males and females is, therefore, apparently attributable to the size and shape of the Golgi apparatus, and is controlled by the estrogen level.     

The solution structure of ω-Aga-IVB,a P-type calcium channel antagonist from venom of the funnel web spider,Agelenopsis aperta

Summary The 48 amino acid peptides -Aga-IVA and -Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of -Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded -sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 Å, two of which are well-defined type-II -turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, -Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel.Abbreviations TOCSY total correlated spectroscopy - NOESY nuclear Overhauser enhancement spectroscopy - COSY correlated spectroscopy