Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events

PurposeTo assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events.Materials and MethodsThis multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS).ResultsTIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476–1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively.ConclusionsAlthough TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.     

Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

基于pH梯度载药技术的咪喹莫特脂质体的制备工艺研究

目的 根据咪喹莫特的理化性质,利用pH梯度主动载药技术制备脂质体,考察其性状、粒径、表面电荷及体外释药特征。方法 葡聚糖凝胶滤过法测定脂质体的包封率,以包封率与成型性为主要指标筛选制备方法,考察水化液的种类、pH值、离子强度及pH梯度载药、磷脂-胆固醇比例、脂药比、维生素E用量对包封率的影响;正交试验优化咪喹莫特脂质体的处方,考察脂质体样品在0~4℃下的稳定性。结果 按处方咪喹莫特50 mg、大豆卵磷脂400 mg、胆固醇130 mg、油酸10 mg、维生素E 5 mg、柠檬酸pH 2.5缓冲液5 mL,采用薄膜分散法工艺制备脂质体样品,并进行pH梯度主动载药,pH值调至7.0。制得的咪喹莫特脂质体呈白色均匀的混悬液,脂质体微粒圆整,分散性好,粒径（347±21）nm,包封率（81.2±1.9）%,Zeta电位（-12.19±1.7）mV。结论 pH梯度主动载药技术适于咪喹莫特脂质体的制备。     

Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy

To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as ‘micelle pool’ drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.     

Automated FRET quantification shows distinct subcellular ERK activation kinetics in response to graded EGFR signaling in Drosophila

Threshold responses to an activity gradient allow a single signaling pathway to yield multiple outcomes. Extracellular signal‐regulated kinase (ERK) is one such signal, which couples receptor tyrosine kinase signaling with multiple cellular responses in various developmental processes. Recent advances in the development of fluorescent biosensors for live imaging have enabled the signaling activities accompanying embryonic development to be monitored in real time. Here, we used an automated computational program to quantify the signals of a fluorescence resonance energy transfer (FRET) reporter for activated ERK, and we used this system to monitor the spatio‐temporal dynamics of ERK during neuroectoderm patterning in Drosophila embryos. We found that the cytoplasmic and nuclear ERK activity gradients show distinct kinetics in response to epidermal growth factor receptor activation. The ERK activation patterns implied that the cytoplasmic ERK activity is modulated into a threshold response in the nucleus.     

Sphere梯度孔结构力学性能有限元分析

建立不同孔径分布的钛合金梯度多孔结构的三维有限元模型,对力学性能进行分析。使用Rhino 5.0和ABAQUS 6.1软件,分别建立sphere、sphere_line、sphere_plane、sphere_point等4种按不同梯度分布的多孔结构有限元模型。对模型分别加载200、400、600、800、1000 N的力,加载力作用于上表面,方向垂直于表面向下,选定下表面为固定约束,计算等效应力及最大主应力。在加载力相同的情况下,sphere_plane梯度孔模型的最大主应力及最大等效应力最大;其次为sphere_point梯度孔模型,较sphere_plane梯度孔模型小42.49%和23.61%;sphere_line梯度孔模型再次之,较sphere_plane梯度孔模型小47.60%和33.12%;sphere无梯度孔模型的最大主应力及最大等效应力最小,较sphere_plane梯度孔模型小68.44%和54.13%。在4种不同梯度孔径分布的多孔结构中,sphere无梯度孔结构的实际受力最小、承载能力最好,其次是sphere_line梯度孔结构,再次是sphere_point梯度孔结构次之,sphere_plane梯度孔结构实际受力最大,其承载能力相比前3种要差。最后通过快速原型对设计出的4种模型进行制备,得到多孔钛合金实体,并对实体进行力学性能测试实验,得出的结论可验证数值模拟分析结果的可靠性。该研究结果可为多孔钛合金植入体设计以及临床应用提供相关设计参考和理论依据。     

Dynamics of Sodium Ions and Water in Swollen Superabsorbent Hydrogels as Studied by 23Na‐ and 1H‐NMR

Dynamics of sodium ions and water in swollen superabsorbent polymer (SAP) hydrogels are studied by ²³Na‐ and ¹H‐NMR, respectively. The apparent diffusion coefficients of water in swollen SAPs, probed by ¹H pulsed field gradient NMR, decreases with increasing diffusion time. The degree of hindrance depends on structural and synthesis parameters. It is quantified within a tortuosity model. Based on the results, the swelling degree has the highest impact on the ion mobility, apart from synthesis parameters leading to different levels of physical and chemical crosslinks. ²³Na‐NMR relaxation and diffusion reveal the ²³Na⁺ mobility in swollen SAPs. A higher degree of neutralization leads to faster relaxation and to a smaller apparent diffusion coefficient. Surface crosslinking restricts water mobility, but has a smaller impact on the dynamics of sodium ions. The experimental results indicate an influence of SAP structure on the dynamics of ions and water molecules.     

乌头叶面细菌、真菌DGGE分析条件的建立与优化

目的:筛选并优化适用于分析乌头叶面细菌、真菌多样性的变性梯度凝胶电泳(DGGE)实验条件。方法:采用Touch Down-PCR技术扩增乌头叶面细菌16 S r DNA V3区域和真菌18 S r DNA~5.8 S r DNA序列,利用该扩增产物对乌头叶面细菌、真菌DGGE电泳条件进行优化。采用DGGE垂直电泳法筛选凝胶变性梯度,时间间隔法优化电泳时间。结果:乌头叶面细菌DGGE最佳分析条件为变性剂梯度30%~65%(Gel 10%),电泳温度60℃,电压120 V,电泳时间7 h。乌头叶面真菌DGGE最佳分析条件为变性剂梯度25%~45%(Gel 8%),电泳温度60℃,电压120 V,电泳时间10 h。结论:利用以上优化条件能有效分离乌头叶面细菌16 S r DNA V3区及真菌18 S r DNA~5.8 S r DNA序列,为乌头叶面细菌,真菌的群落结构PCR-DGGE分析提供可靠的技术支撑。     

Gradients in periodontal status in Japanese employed males

AIM: The objective was to assess whether there was a social gradient in periodontal status by job classification in Japanese male workers. MATERIAL AND METHODS: Study participants were 15,803 Japanese male workers aged 20-69 years. There were seven groups classified by jobs. Oral examinations were conducted using community periodontal index (CPI). RESULTS: The percentages of sextants with a CPI score of 3 or 4 of professionals were significantly lower than for other job classes. The gradient also existed for the percentage of sextants with CPI score 4. After adjusting for age, a history of diabetes mellitus and smoking status, those lower on the gradient, namely, drivers, service occupations, salespersons and managers were 2.0, 1.5, 1.4 and 1.4, times, respectively more likely to have one or more sextants with CPI score 3 or 4 compared with professionals. Odds ratios of having more than one or more sextants with CPI score 4 after adjusting for age, clinical history of diabetes mellitus and smoking status for drivers, service occupations, salespersons and managers were 2.1, 1.5, 1.5 and 1.2, respectively, compared with professionals. CONCLUSIONS: There was a gradient in periodontal status by job classification. Professional and office workers had better periodontal status than salespersons, service occupations and drivers.     

钛及钛合金表面制备羟磷灰石梯度涂层的研究进展

羟磷灰石(HA)常涂覆于钛及钛合金表面使其获得良好的力学和生物学性能,HA梯度涂层的研制为解决HA和钛及钛合金热膨胀系数不匹配的问题提供途径.本文就钛及钛合金表面制备HA梯度涂层的研究进展作一综述.