We report an amphiphilic block copolymer via poly(ethylene glycol) methyl ether-Dlabile-poly(caprolactone)-ferrocene (mPEG-Dlabile-PCL-Fc) to deliver anticancer drug doxorubicin (DOX). Lipase ...Novozyme-435 was used as a catalyst for ring-opening polymerization with ε-caprolactone, and an acid-sensitive Schiff base was used to connect the hydrophilic and hydrophobic parts; the ferrocene provided ferrous ions and was introduced at the end of the amphiphilic copolymer. The resulting copolymers were characterized by 1H NMR/13C NMR and could be self-assembled in an aqueous solution to form nanomicelles with PCL-Fc as a hydrophobic core and mPEG as a hydrophilic shell. Transmission electron microscopy showed that the micelles were spherical and nanosized before and after DOX loading. The blank micelles also showed good biocompatibility. The drug-loaded polymeric nanomicelles exhibited a positive anticancer effect relative to the copolymers without ferrocene; the therapeutic effect of drug-loaded micelles containing ferrocene was more obvious. In vitro drug release results also showed that the polymer had a good pH response. Confocal microscopy also showed that polymeric micelles can effectively deliver and release the drug; the polymer containing ferrocene also leads to significantly improved ROS levels in tumor cells. Ferrocene can effectively and synergistically inhibit tumor cells with DOX.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Despite numerous studies, the impact of global warming on the tropical cyclone (TC) track and intensity by reasons of data inhomogeneity in remote sensing and large natural variability over a ...relatively short period of observation is still controversial. Three carbon-emission sensitivity experiments are conducted to investigate how TC track and intensity respond to changes in the oceanic and atmospheric environment under global warming. The results show a high sensitivity of the simulated TC track and intensity to global warming. On one hand, with increase in carbon emissions, the western Pacific subtropical high expands notably, increasing the poleward steering flow and eventually leading to a poleward shift of TC. On the other hand, the underlying sea-surface temperature and surface-entropy flux increase and, thus, favor the convections near the eyewall. Moreover, the TC structure becomes more upright, which is closely related to the larger pressure gradient near the eyewall. As a result, TC intensity increases with carbon emissions. However, this increase is notably smaller than the maximum potential intensity theory as the TC intensity can reach a threshold if carbon emission still increases in the future. The involved mechanisms on the changes of TC track and intensity are also revealed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic.
To ...investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR.
Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS.
Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.
Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with ...heatstroke and its impact on outcomes.
To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes.
Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms.
A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms.
The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.
The objective of this study was to investigate the effects of explosion puffing on the nutritional composition, physical properties, and digestibility of grains including millet, barley, black rice, ...rice, glutinous rice, and wheat. Explosion puffing of grains resulted in the nutritional composition with higher total sugar content and lower moisture, starch and fat contents. Although the protein content scarcely changed comparing with the untreated grains, the solubility declined significantly. Moreover, explosion puffing could significantly improve the physical properties including the water absorption index, water solubility index and gelatinization degree. The in vitro digestion experiment was employed to investigate the influences of explosion puffing on the starch hydrolysis rate and free amino acid content, and it was indicated that the digestibility of the starch and protein in grains was highly improved. The results demonstrated that explosion puffing is a suitable technique to improve the physical properties and digestibility of grains, which provided the theoretic foundation for the use of explosion puffing technology in coarse cereal processing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the ...Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
To assess the therapeutic effect of a novel tension band using 3.0 mm cannulated screw combined with a titanium cable and specific shims comparatively with patellotibial tubercle cerclage ...in comminuted fractures of the inferior pole of the patella.
Methods
The retrospective study from March 2012 to July 2017 was conducted in Peking University Third Hospital and comprised 63 patients with comminuted fractures of the inferior pole of the patella: 41 treated with new tension band using 3.0 mm cannulated screw combined with a titanium cable and specific shims (new tension band group) and 22 with patellotibial tubercle cerclage (tubercle cerclage group). Gender, age, AO/OTA fracture type, injury mechanism, inter‐fragmentary gap, and follow‐up time of patients were recorded. Two groups were compared regarding: operation time, blood loss, partial weight‐bearing time, fracture‐healed time, Bostman score and knee mobility at 12‐month follow‐up, and postoperative complications. Continuous and categorical parameters were analyzed by Mann‐Whitney U test and the chi‐squared test, respectively. Fisher's exact test was used for small data subsets.
Results
Between the two groups, no statistically significant difference was found in mean age, gender, AO/OTA fracture type, injury mechanism, mean inter‐fragmentary gap, or mean follow‐up time (P > 0.05). The mean operation time of new tension band group was significantly longer than that of tubercle cerclage group (76.4 min vs 64.2 min, P = 0.006), while there was no significant difference in blood loss. After surgery, new tension band group had a significantly earlier mean partial weight‐bearing time (5.2 weeks vs 7.4 weeks, P < 0.001) and fracture‐healed time (9.6 weeks vs 11.6 weeks, P < 0.001). At 12‐month follow‐up, patients of new tension band group had a significantly higher mean Bostman score (28.5 vs 25.8, P < 0.001) and knee mobility (126.7 vs 117.3, P < 0.001). Ten complications related with internal fixation were found in tubercle cerclage group including two cases of loose internal fixation, two cases of cerclage breakage, and six cases of low patella position who undertook secondary operation. No complications were found in new tension band group (0 in 41 vs 10 in 22, P < 0.001).
Conclusion
Patients with comminuted fractures of the inferior pole of the patella treated with a novel tension band experienced a longer operation time, but earlier partial‐weight‐bearing and fracture‐healed time, better clinical outcomes at 12‐month follow‐up, and less complications. It should be considered an alternative therapy for the treatment of distal pole patellar fractures.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The rapid diagnosis and surgical prediction of necrotizing enterocolitis (NEC) remain a challenge because its complex pathogenesis has not been completely elucidated, and no single medical ...examination is specific for diagnosing NEC. Artificial intelligence (AI) has proven the robustness of multivariate analysis and been widely used in the diagnosis of complex diseases in the past decade. In this paper, a new multimodal AI system including feature engineering, machine learning (ML), and deep learning (DL) was constructed based on abdominal radiographs (ARs) and clinical data. A total of 4,535 ARs from 1,823 suspected NEC patients were analyzed by transfer learning, and then medical images and clinical parameters from 827 suspected NEC patients were used to train, validate, and test the AI system. Our results demonstrated that the system was effective in diagnosing NEC. In addition, the clinical datasets obtained one week before surgery from 379 NEC patients were studied by the multimodal AI system, and the results showed that it was capable of predicting which NEC patients required surgery. We compared the results in external test sets with those made by clinicians and found that the diagnostic and surgical predictive ability of the AI system was equivalent to that of experienced clinicians. This multimodal AI system can help clinicians improve diagnostic efficiency, reduce the number of missed diagnoses, and facilitate early diagnosis and treatment to prevent disease progression or even death.
Increasing evidence supports that microRNA (miRNA) plays a significant functional role in cancer progression by directly regulating respective targets. In this study, the expression levels of ...miR-105-1 and its target gene were analyzed using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR in hepatocellular carcinoma (HCC) and normal liver tissues. We examined the expression of nuclear receptor coactivator 1 (NCOA1), the potential target gene of miR-105-1, following the transfection of miR-105-1 mimics or inhibitors. Our results showed that miR-105-1 was downregulated in HCC tissues when compared with normal liver tissues and patients with lower miR-105-1 expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, NCOA1 was confirmed to be a direct target of miR-105-1. Furthermore, concomitant high expression of NCOA1 and low expression of miR-105-1 correlated with a shorter median OS and PFS in HCC patients. In conclusion, our results provide the first evidence that NCOA1 is a direct target of miR-105-1 suggesting that NCOA1 and miR-105-1 may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of HCC patients.
Background: Cardiovascular diseases (CVD) are the leading cause of death globally. Electrocardiogram (ECG) analysis can provide thoroughly assessment for different CVDs efficiently. We propose a ...multi-task group bidirectional long short-term memory (MTGBi-LSTM) framework to intelligent recognize multiple CVDs based on multi-lead ECG signals. Methods: This model employs a Group Bi-LSTM (GBi-LSTM) and Residual Group Convolutional Neural Network (Res-GCNN) to learn the dual feature representation of ECG space and time series. GBi-LSTM is divided into Global Bi-LSTM and Intra-Group Bi-LSTM, which can learn the features of each ECG lead and the relationship between leads. Then, through attention mechanism, the different lead information of ECG is integrated to make the model to possess the powerful feature discriminability. Through multi-task learning, the model can fully mine the association information between diseases and obtain more accurate diagnostic results. In addition, we propose a dynamic weighted loss function to better quantify the loss to overcome the imbalance between classes. Results: Based on more than 170,000 clinical 12-lead ECG analysis, the MTGBi-LSTM method achieved accuracy, precision, recall and F1 of 88.86%, 90.67%, 94.19% and 92.39%, respectively. The experimental results show that the proposed MTGBi-LSTM method can reliably realize ECG analysis and provide an effective tool for computer-aided diagnosis of CVD.
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