Novel colloidal associations of soyasaponins and lipid components (DPPC,cholesterol) as potential adjuvants for vaccines

Soyasaponins from soybean (Glycine max) represent promising new potent adjuvants for vaccine research because of their immunostimulating properties and weak hemolytic activity. In the present study, saponin microstructures of soyasaponins (soyasaponin Bb, soyasaponin Ab) with lipid components (cholesterol, DPPC (dipalmitoylphosphatidylcholine)) were designed by the lipid film method. In interaction studies between soyasaponins (soyasaponin Ab/Bb) and Langmuir monolayers (model membranes), composed of cholesterol and DPPC, marked interactions between soyasaponins and a pure cholesterol monolayer were observed. No interaction was detected for soyasaponins with a pure DPPC monolayer. The intercalation of soyasaponins in a mixed DPPC/cholesterol (3:1, w/w) monolayer was only observed for the monodesmosidic soyasaponin Bb whereas the second sugar chain of the bidesmosidic soyasaponin Ab impaired the access to the monolayer. Transmission electron microscopy was used for visualizing particle formation of soyasaponins and lipid components. Pseudo-binary systems (soyasaponin Ab/Bb, cholesterol) formed colloidal associations built up from ring-like subunits in the nanometer size range. In pseudo-ternary systems (soyasaponin, cholesterol, DPPC) soyasaponin Bb attacked the liposomal membrane by forming colloidal associations. Colloidal associations in pseudo-ternary systems with soyasaponin Ab, cholesterol and a phospholipid were only observed in the presence of PE (phosphatidylethanolamine) instead of DPPC. In an MTT assay with a HaCaT cell line (keratinocyte cell line) the cell viability was neither affected by the soyasaponins nor by the corresponding formulations. Both the pure soyasaponin solution and the saponin formulations may be promising adjuvant systems for the intradermal vaccine application. Furthermore, interaction studies between the model antigen ovalbumin and colloidal associations of saponins and cholesterol using MST (Microscale Thermophoresis) gave first indications of an antigen binding to colloidal associations. Ex vivo T-cell proliferation in the presence of soyasaponin Ab was confirmed.     

蒙花苷磷脂复合物的制备及其药动学评价

目的 制备蒙花苷磷脂复合物，研究其药动学性质。方法 溶剂挥发法制备蒙花苷磷脂复合物，以复合率为评价指标，通过正交试验优化制备工艺。SD大鼠灌胃给予蒙花苷磷脂复合物，HPLC测定蒙花苷的血药浓度。结果 采用优化后的磷脂复合物制备工艺，复合率接近100%。X射线衍射结果表明蒙花苷以无定型状态存在于磷脂复合物中，在水和正辛醇中的表观溶解度显著增大。药动学结果显示，蒙花苷磷脂复合物的t_max，C_max，AUC_0-t等参数与蒙花苷原料药相比具有显著性差异，口服吸收生物利用度提高1.11倍。结论 磷脂复合物改善了蒙花苷的溶解性质，口服吸收生物利用度得到明显提高。     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.     

非同步处理肾蒂血管技术在后腹腔镜复杂性肾癌肾盂癌根治术中的应用探讨

目的:探讨经后腹腔入路行腹腔镜复杂性肾癌肾盂癌根治术肾蒂血管非同步处理技巧。方法:2010年1月至2018 年 4月就诊于我科的109例肾癌、肾盂癌患者接受腹膜后入路腹腔镜根治性肾切除术。根据肾蒂血管处理方式的差异分别纳入非同步组和同步组。非同步组患者61例，其中肾癌43例，肾盂癌18例；同步组患者48例，其中肾癌33例，肾盂癌15例；均采用3套管技术，从腹膜后入路，显露肾蒂，非同步组优先处理肾动脉，游离肾脏，最后结扎肾静脉。同步组先游离出肾动脉及肾静脉予以结扎，最后游离肾脏。分别对两组患者的手术时间、术中失血量进行统计分析。结果:非同步组1例男性患者因左肾肉瘤浸润腰大肌、腹膜及结肠，粘连严重转为开放手术，予以排除，两组其余患者均顺利完成手术。非同步组与同步组手术时间分别为:肾癌（94.3±28.1）min vs （113.3±40.3）min，肾盂癌（135.2±43.3）min vs （168.2±37.2）min；术中出血量分别为:肾癌（68.4±56.8）ml vs （100.7±93.1）ml，肾盂癌（105.4±37.3）ml vs （131.3±36.3）ml。比较两组患者病种间手术时间及术中出血量均有统计学差异（P<0.05）。结论:肾蒂血管的处理是复杂性肾癌、肾盂癌经后腹腔镜根治切除的关键，术中灵活的肾血管处理应对尤为重要，非同步肾蒂血管处理技巧有助于减少术中出血量，缩短手术时间，增加手术安全性。     

Acute Colonic Diverticulitis and Cirrhosis: Outcomes of Laparoscopic Colectomy Compared with an Open Approach

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