Biodegradable double-network GelMA-ACNM hydrogel microneedles for transdermal drug delivery.

As a minimally invasive drug delivery platform, microneedles (MNs) overcome many drawbacks of the conventional transdermal drug delivery systems, therefore are favorable in biomedical applications. Microneedles with a combined burst and sustained release profile and maintained therapeutic molecular bioactivity could further broaden its applications as therapeutics. Here, we developed a double-network microneedles (DN MNs) based on gelatin methacrylate and acellular neural matrix (GelMA-ACNM). ACNM could function as an early drug release matrix, whereas the addition of GelMA facilitates sustained drug release. In particular, the double-network microneedles comprising GelMA-ACNM hydrogel has distinctive biological features in maintaining drug activity to meet the needs of application in treating different diseases. In this study, we prepared the double-network microneedles and evaluated its morphology, mechanical properties, drug release properties and biocompatibility, which shows great potential for delivery of therapeutic molecules that needs different release profiles in transdermal treatment.

Continuous Blood Pressure Estimation Based on Multi-Scale Feature Extraction by the Neural Network With Multi-Task Learning.

In this article, a novel method for continuous blood pressure (BP) estimation based on multi-scale feature extraction by the neural network with multi-task learning (MST-net) has been proposed and evaluated. First, we preprocess the target (Electrocardiograph; Photoplethysmography) and label signals (arterial blood pressure), especially using peak-to-peak time limits of signals to eliminate the interference of the false peak. Then, we design a MST-net to extract multi-scale features related to BP, fully excavate and learn the relationship between multi-scale features and BP, and then estimate three BP values simultaneously. Finally, the performance of the developed neural network is verified by using a public multi-parameter intelligent monitoring waveform database. The results show that the mean absolute error ± standard deviation for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) with the proposed method against reference are 4.04 ± 5.81, 2.29 ± 3.55, and 2.46 ± 3.58 mmHg, respectively; the correlation coefficients of SBP, DBP, and MAP are 0.96, 0.92, and 0.94, respectively, which meet the Association for the Advancement of Medical Instrumentation standard and reach A level of the British Hypertension Society standard. This study provides insights into the improvement of accuracy and efficiency of a continuous BP estimation method with a simple structure and without calibration. The proposed algorithm for BP estimation could potentially enable continuous BP monitoring by mobile health devices.

Codelivery of epigallocatechin-3-gallate and diallyl trisulfide by near-infrared light-responsive mesoporous polydopamine nanoparticles for enhanced antitumor efficacy.

Green tea extract epigallocatechin-3-gallate (EGCG), as a kind of natural active compounds, has become a research hotspot in cancer treatment. However, poor stability, low bioavailability and antitumor efficacy limit the application of EGCG. In this study, mesoporous dopamine (MPDA) with high drug loading and good biocompatibility loaded EGCG, garlic extract diallyl trisulfide (DATS) and photosensitizer (indocyanine green, ICG) by π-π stacking and hydrophobic-hydrophobic interaction, and the nano-system involved filling the mesoporous of the MPDA with phase change material (1-tetradecanol, 1-TD) molecules, which acted as a thermosensitive gatekeeper. The results indicated that MPDA-ICG@TD has an excellent photothermal effect and good stability. Due to the solid-liquid phase transition characteristics of the phase change material, MPDA-ICG@TD could control the release of drugs under near-infrared laser irradiation. Besides, cytotoxicity and apoptosis experiments showed that MPDA-ICG/EGCG/DATS@TD could be efficiently inhibited 4T1 cell proliferation and accelerate cell apoptosis than use diallyl trisulfide or EGCG alone, which means that the combination of natural active compounds EGCG and diallyl trisulfide has excellent synergy and can effectively improve the antitumor effect of EGCG. Moreover, this nano-system exhibited non-toxicity and good blood compatibility. This study provides a promising and effective strategy for improving the antitumor efficacy of natural active compound EGCG.

Comparison of a New High-Frequency Electric Welding System for Intestinal Closure with Hand-Sewn In Vivo Pig Model.

BACKGROUND: Various surgical small intestinal anastomosis methods are in current use, but improvements are always desired. Thus, we compared the feasibility, effectiveness, and safety of a new high-frequency electric welding (HFEW) system for sealing the small bowel versus a hand-sewn in vivo pig model. MATERIALS AND METHODS: The 96 bowel segments of three pigs were randomized to be sutured either by the HFEW-300 PATONMED device (E.O. Paton Electric Welding Institute of the National Academy of Sciences of Ukraine, Kiev, Ukraine) or hand-sewn, and mucosa-to-mucosa fusions were subjected in vivo testing in the pigs. Bursting pressures, suture time, thermal damage, and the temperature of sealed ends were measured. RESULTS: Segments that had been treated with a hand-sutured ligature or double-sealed with HFEW were compared. Burst pressure was significantly higher in the hand-sutured group than in the HFEW group (136.2 mm Hg versus 75.8 mm Hg, P<.01). All 48 pig small bowels closed by the HFEW-300 generator showed a success rate of 100.0%. The closing time in the HFEW group was significantly shorter (P<.01). The pathological changes of the closed ends were mainly presented as acute thermal- and pressure-induced injuries. CONCLUSIONS: Outcomes of the current in vivo study suggest that HFEW is an effective and safe method for ligation of the small bowel in pigs.

Overexpression of HMGA1 correlates with the malignant status and prognosis of breast cancer.

High mobility group A1 (HMGA1), as a major member of HMGA family, plays an important part in promotion of cell proliferation and motility, induction of epithelial-mesenchymal transition, and maintenance of stemness, but little is known about the pathological role of HMGA1 in breast cancer patients. The aim of this study was to identify the pathological roles of HMGA1 in breast cancer. In our results, we found that mRNA and protein expression levels of HMGA1 were markedly higher in breast cancer tissues than in normal breast tissues. Using immunohistochemistry, high levels of HMGA1 protein were positively correlated with the status of histological grade (I-II vs. III-IV; P = 0.023), clinical stage (I-II vs. III-IV; P = 0.008), tumor size (T1-T2 vs. T3-T4; P = 0.015), lymph node metastasis (N0-N1 vs. N2-N3; P = 0.002), distant metastasis (M0 vs. M1; P < 0.001), and triple-negative breast cancer (No vs. Yes; P = 0.014) of breast cancer patients. Patients with higher HMGA1 expression had a significantly shorter overall survival time than did patients with low HMGA1 expression. Multivariate analysis indicated that the level of HMGA1 expression was an independent prognostic indicator (P < 0.001) for the survival of patients with breast cancer. In conclusion, HMGA1 plays an important role on breast cancer aggressiveness and prognosis and may act as a promising target for prognostic prediction.

[A Feasibility Study of closing the small bowel with high-frequency welding device].

This study aimed to evaluate the feasibility and effectiveness of closing the small bowel in an ex vivo porcine model with high-frequency welding device. A total of 100 porcine small bowels were divided into two groups, and then were closed with two different methods. The fifty small bowels in experimental group were closed by the high-frequency welding device, and the other fifty small bowels in comparison group were hand-sutured. All the small bowels were subjected to leak pressure testing later on. The speed of closure and bursting pressure were compared. The 50 porcine small bowels closed by the high-frequency welding device showed a success rate of 100%. Compared with the hand-sutured group, the bursting pressures of the former were significantly lower (P<0.01) and the closing process was significantly shorter (P<0.01). The pathological changes of the closed ends mainly presented as acute thermal and pressure induced injury. Experimental results show that the high-frequency welding device has higher feasibility in closing the small bowel.