Local magnetic delivery of adeno-associated virus AAV2(quad Y-F)-mediated BDNF gene therapy restores hearing after noise injury

1. Download : Download high-res image (159KB)
2. Download : Download full-size image

     

Adherence to Chronic Kidney Disease Screening Guidelines Among Patients With Type 2 Diabetes in a US Administrative Claims Database

ObjectiveTo examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims database.Patients and MethodsThis cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results.ResultsA total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 [43.3%]). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period.ConclusionPhysicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up.     

C反应蛋白和白蛋白比值预测单发小肝癌患者微血管侵犯的价值研究

背景 既往对肝癌微血管侵犯病理诊断的重要性重视不够，目前国内外缺乏对微血管侵犯统一的病理诊断标准，也未将微血管侵犯列为病理常规诊断指标。C反应蛋白/白蛋白比值（CAR）作为新型系统性炎性因子，与肝癌的增殖、侵袭转移等恶性生物学行为密切相关。 目的 探讨CAR预测单发小肝癌患者微血管侵犯的价值。 方法 选择2017年6月至2021年6月在新疆医科大学第一附属医院行肝切除术的单个、肿瘤直径≤5 cm的术后病理检查证实为肝癌的患者346例为研究对象。收集患者一般资料，并计算CAR。绘制CAR预测单发小肝癌患者微血管侵犯的受试者工作特征（ROC）曲线，并计算CAR的最佳诊断截点，根据CAR最佳诊断截点将患者进行分组，采用1∶1最近邻居倾向性评分匹配（PSM）法将Logistic模型估计的倾向性评分相近患者进行配对，得到两组间各临床特征比较均衡性较高的样本。比较匹配后两组患者微血管侵犯率，采用Logistic回归分析评估匹配前、后CAR对单发小肝癌患者微血管侵犯的预测价值。 结果 346例患者中微血管侵犯阳性131例（37.9%），微血管侵犯阴性215例（62.1%）。ROC曲线分析结果显示，CAR预测单发小肝癌患者微血管侵犯的灵敏度为82.9%，特异度为76.4%，ROC曲线下面积为0.787〔95%CI（0.697，0.877）〕，最佳诊断截点为0.03。根据CAR最佳诊断截点，将患者分为CAR<0.03组（A组，n=145）和CAR≥0.03组（B组，n=201）。采用1∶1最近邻居PSM法，共92对匹配成功，匹配后两组临床资料均衡。匹配后，B组患者微血管侵犯发生率〔43.5%（40/92）〕高于A组〔13.0%（12/92）〕（χ2=6.314，P=0.013）。采用3种Logistic回归分析结果显示，匹配前、后CAR均为单发小肝癌患者微血管侵犯的独立影响因素（P<0.05）。 结论 CAR作为新型系统性炎症指标，可用于预测单发小肝癌微血管侵犯，当CAR≥0.03时提示单发小肝癌微血管侵犯发生率较高。     

Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells

1. Download : Download high-res image (179KB)
2. Download : Download full-size image

     

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Stabilization and formulation of a recombinant Human Cytomegalovirus vector for use as a candidate HIV-1 vaccine

Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials.     

Concurrent removal of Cr(III), Cu(II), and Pb(II) ions from water by multifunctional TiO2/Alg/FeNPs beads

The use of multifunctional materials for water remediation is a modern approach where adsorption phenomena and heterogeneous photocatalysis can be applied for the removal of pollutants. Since the ideal remediation system should be able to remove both organic and inorganic pollutants, a crucial aspect to consider is the knowledge of operational parameters affecting the removal process, especially when heavy metal ions are present in concoction as in real systems. Given the proven efficiency of multifunctional TiO₂/Alg/FeNPs magnetic beads for the removal of model organic pollutants, this study investigated the possibility to exploit such system also for the removal of mixed heavy metals (MHM), specifically Cr(III), Cu(II), and Pb(II) ions, under ultraviolet irradiation at a wavelength of 254 nm. After a preliminary screening on the optimal catalyst loading, operating parameters such as the initial concentration of metal ions, contact and irradiation time, and pH were investigated to optimize the removal of metal ions using response surface methodology (RSM) via Box–Behnken design. Starting from a MHM solution containing 44 ppm of each metal ion, the removal of Pb(II), Cr(III), and Cu(II) ions in the aqueous solution was nearly completed (>98.4%) for all three ions within 72 min of irradiation at almost neutral pH (pH = 6.8). The stability of TiO₂/Alg/FeNPs was confirmed by retrieving and reusing the beads in three consecutive cycles of heavy metals removal without observing significant changes in catalyst efficiency.     

Lycopene and resveratrol ameliorate zinc oxide nanoparticles-induced oxidative stress in Nile tilapia,Oreochromis niloticus

Industrial products contained nano-zinc oxide (ZnONP) can gain access to the aquaculture environment causing hazardous effects on the living biota. Therefore, this work was planned to examine the ameliorative effects of dietary supplementation of lycopene (LYC) and/or resveratrol (RES) against ZnONP toxicity in Nile tilapia. Five groups with 20 fish each were used; Control, received tap water only; ZnONP group, was intoxicated with ZnONP (50 mg/L); ZnONP-LYC group, was exposed to ZnONP and LYC (500 mg/ kg of the diet); ZnONP-RES group, was exposed to ZnONP and RES (50 mg/kg of the diet); ZnONP-LYC-RES group, was exposed to ZnONP and a combination of LYC and RES. The experiment was continued for 30 days. Fish blood and tissues were then assembled for determination of liver and kidney function and oxidative stress status in liver, kidney, and gills tissue. Results revealed a considerable elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol, urea, and creatinine with a noticeable lowering of total proteins and albumin serum levels in response to ZnONP intoxication. In addition, there were significant increase in malondialdehyde (MDA) and reduction in the reduced-glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities. However, treatment with LYC and/or RES ameliorated the ZnONP-inflicted oxidative stress which possibly attributed to their beneficial antioxidant activities.