Enhancing the Repair of Substantial Volumetric Muscle Loss by Creating Different Levels of Blood Vessel Networks Using Pre-Vascularized Nerve Hydrogel Implants.

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.

Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.

Developing scalable vascularized and innervated tissue is a critical challenge for the successful clinical application of tissue-engineered constructs. Collagen hydrogels are extensively utilized in cell-mediated vascular network formation because of their naturally excellent biological properties. However, the substantial increase in hydrogel contraction induced by populated cells limits their long-term use. Previous studies attempted to mitigate this issue by concentrating collagen pre-polymer solutions or synthesizing covalently crosslinked collagen hydrogels. However, these methods only partially reduce hydrogel contraction while hindering blood vessel formation within the hydrogels. To address this challenge, we introduced additional support in the form of a supportive spacer to counteract the contraction forces of populated cells and prevent hydrogel contraction. This approach was found to promote cell spreading, resist hydrogel contraction, control hydrogel/tissue geometry, and even facilitate the engineering of functional blood vessels and host nerve growth in just one week. Subsequently, implanting these engineered tissues into muscle defect sites resulted in timely anastomosis with the host vasculature, leading to enhanced myogenesis, increased muscle innervation, and the restoration of injured muscle functionality. Overall, this innovative strategy expands the applicability of collagen hydrogels in fabricating large vascularized nerve tissue constructs for repairing volumetric muscle loss (∼63 %) and restoring muscle function.

Predicting weaning difficulty for planned extubation patients with an artificial neural network.

This study aims to construct a neural network to predict weaning difficulty among planned extubation patients in intensive care units.This observational cohort study was conducted in eight adult ICUs in a medical center about adult patients experiencing planned extubation.The data of 3602 patients with planned extubation in ICUs of Chi-Mei Medical Center (from Dec. 2009 through Dec. 2011) was used to train and test an artificial neural network (ANN) model. The input features contain 47 clinical risk factors and the outputs are classified into three categories: simple, difficult, and prolonged weaning. A deep ANN model with four hidden layers of 30 neurons each was developed. The accuracy is 0.769 and the area under receiver operating characteristic curve for simple weaning, prolonged weaning, and difficult weaning are 0.910, 0.849, and 0.942 respectively.The results revealed that the ANN model achieved a good performance in prediction the weaning difficulty in planned extubation patients. Such a model will be helpful for predicting ICU patients' successful planned extubation.

Comparison of machine learning models for the prediction of mortality of patients with unplanned extubation in intensive care units.

Unplanned extubation (UE) can be associated with fatal outcome; however, an accurate model for predicting the mortality of UE patients in intensive care units (ICU) is lacking. Therefore, we aim to compare the performances of various machine learning models and conventional parameters to predict the mortality of UE patients in the ICU. A total of 341 patients with UE in ICUs of Chi-Mei Medical Center between December 2008 and July 2017 were enrolled and their demographic features, clinical manifestations, and outcomes were collected for analysis. Four machine learning models including artificial neural networks, logistic regression models, random forest models, and support vector machines were constructed and their predictive performances were compared with each other and conventional parameters. Of the 341 UE patients included in the study, the ICU mortality rate is 17.6%. The random forest model is determined to be the most suitable model for this dataset with F1 0.860, precision 0.882, and recall 0.850 in the test set, and an area under receiver operating characteristic (ROC) curve of 0.910 (SE: 0.022, 95% CI: 0.867-0.954). The area under ROC curves of the random forest model was significantly greater than that of Acute Physiology and Chronic Health Evaluation (APACHE) II (0.779, 95% CI: 0.716-0.841), Therapeutic Intervention Scoring System (TISS) (0.645, 95% CI: 0.564-0.726), and Glasgow Coma scales (0.577, 95%: CI 0.497-0.657). The results revealed that the random forest model was the best model to predict the mortality of UE patients in ICUs.

An Artificial Neural Network Model for Predicting Successful Extubation in Intensive Care Units.

BACKGROUND: Successful weaning from mechanical ventilation is important for patients in intensive care units (ICUs). The aim was to construct neural networks to predict successful extubation in ventilated patients in ICUs. METHODS: Data from 1/12/2009 through 31/12/2011 of 3602 patients with planned extubation in Chi-Mei Medical Center's ICUs was used to train and test an artificial neural network (ANN). The input was 37 clinical risk factors, and the output was a failed extubation prediction. RESULTS: One hundred eighty-five patients (5.1%) had a failed extubation. Multivariate analyses revealed that failure was positively associated with therapeutic intervention scoring system (TISS) scores (odds ratio [OR]: 1.814; 95% Confidence Interval [CI]: 1.283⁻2.563), chronic hemodialysis (OR: 12.264; 95% CI: 8.556⁻17.580), rapid shallow breathing (RSI) (OR: 2.003; 95% CI: 1.378⁻2.910), and pre-extubation heart rate (OR: 1.705; 95% CI: 1.173⁻2.480), but negatively associated with pre-extubation PaO2/FiO2 (OR: 0.529; 95%: 0.370⁻0.750) and maximum expiratory pressure (MEP) (OR: 0.610; 95% CI: 0.413⁻0.899). A multilayer perceptron ANN model with 19 neurons in a hidden layer was developed. The overall performance of this model was F1: 0.867, precision: 0.939, and recall: 0.822. The area under the receiver operating characteristic curve (AUC) was 0.85, which is better than any one of the following predictors: TISS: 0.58 (95% CI: 0.54⁻0.62; p < 0.001); 0.58 (95% CI: 0.53⁻0.62; p < 0.001); and RSI: 0.54 (95% CI: 0.49⁻0.58; p = 0.097). CONCLUSIONS: The ANN performed well when predicting failed extubation, and it will help predict successful planned extubation.

Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with meningitis.

PURPOSE: Certain cytokines play important roles in the pathophysiology of meningitis. The main purpose of this study was to investigate if the levels of interleukin-6 (IL-6) and interleukin-12 (IL-12) in cerebrospinal fluid (CSF) could be diagnostic predictors of bacterial meningitis in children. METHODS: CSF was obtained from 95 patients suspected with meningitis. These cases were classified to the bacterial meningitis (n = 12), aseptic meningitis (n = 41), and nonmeningitis (n = 42) groups. The levels of IL-6 and IL-12 in CSF were measured using the enzyme-linked immmunosorbent assays test. RESULTS: The CSF IL-6 levels in the bacterial meningitis group (45.2 +/- 50.0 pg/ml) were significantly higher than those in the aseptic meningitis group (12.9 +/- 10.2 pg/ml) and the nonmeningitis group (6.5 +/- 7.8 pg/ml; p < 0.05). The CSF IL-12 levels in the bacterial meningitis group (69.8 +/- 67.1 pg/ml) were significantly higher than those in the aseptic meningitis group (22.9 +/- 10.8 pg/ml) and the nonmeningitis group (15.3 +/- 11.2 pg/ml; p < 0.05). With regard to diagnosis, the measurement of CSF IL-6 and IL-12 levels showed sensitivities of 96% and 96%, respectively, and specificities of 51% and 75%, respectively. CONCLUSION: It is suggested that the CSF IL-6 and IL-12 levels are useful markers for distinguishing bacterial meningitis from aseptic meningitis.

Schizandrin protects primary cultures of rat cortical cells from glutamate-induced excitotoxicity.

The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 microM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 microM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 microM. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

Changes in serum eosinophil cationic protein levels after exercise challenge in asthmatic children.

The aim of the present study was to assess the relationship between serum eosinophil cationic protein levels and the severity of exercise-induced bronchoconstriction in asthmatic children. The 48 asthmatic children were divided into exercise-induced bronchoconstriction group and non-exercise-induced bronchoconstriction group. In the exercise-induced bronchoconstriction group, the post-exercise serum eosinophil cationic protein levels were significantly increased as compared with the pre-exercise serum eosinophil cationic protein levels. These results suggested that eosinophil cationic protein may serve as a possible contributor to the pathophysiology of exercise-induced bronchoconstriction in asthmatic children.

Ameliorating effect of emodin, a constitute of Polygonatum multiflorum, on cycloheximide-induced impairment of memory consolidation in rats.

The aim of the present study was intended to investigate the ameliorating effects of emodin on memory consolidation via cholinergic, serotonergic and GABAergic neuronal systems in rats. First, we evaluated the ameliorating effects of emodin on cycloheximide (CXM)-induced impairment of passive avoidance response in rats. Secondly, we clarified the role of cholinergic, serotonergic or GABAergic system on the ameliorating effect of emodin by using 5-HT1A receptor partial agonist, 5-HT2 receptor antagonist, GABAB agonist, GABAA antagonist and muscarinic receptor antagonist. Emodin protected the rat from CXM-induced memory consolidation impairment. The beneficial effect of emodin on CXM-induced memory consolidation impairment was amplified by 8-OH-DPAT (5-HT1A receptor partial agonist) and ritanserin (5-HT2 receptor antagonist), but reduced by scopolamine. These results suggested that the beneficial effect of emodin on CXM-induced memory consolidation impairment was amplified by serotonergic 5-HT1A-receptor partial agonist and 5-HT2 receptor antagonist but reduced by muscarinic receptor antagonist.

Effects of luteolin on learning acquisition in rats: involvement of the central cholinergic system.

The study was conducted to investigate the ameliorating effects of luteolin on memory acquisition in rats. The effects of luteolin on scopolamine-induced impairment of passive avoidance response were evaluated primarily, as well as the role of the central nervous system through the use of central neurotoxins and central nervous antagonists. Luteolin was not reversed by scopolamine N-methylbromide (M-SCOP) but blocked the impairment of learning acquisition induced by cholinergic neurotoxin (ethylcholine aziridinium, AF64A) and muscarinic (scopolamine hydrobromide, SCOP) and nicotinic (mecamylamine, MECA) receptor antagonists. However, it did not block dopaminergic neurotoxin (6-hydroxydopamine, 6-OHDA)-induced and serotonergic neurotoxin (5,7-dihydroxytryptamine, 5,7-DHT)-induced impairments. From these results, we suggest that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors.

Differential gene expression in hemodialysis patients with "cold" zheng.

The aim of the present study was to search for the differential gene expression and measure the serum level of a number of biochemical parameters in the cold zheng (CZ) and non-cold zheng (NCZ) in patients receiving hemodialysis. Hemodialysis (HD) patients were randomly selected from the CZ and NCZ groups. The between-group differences in gene expression were assessed using complementary DNA (cDNA) microarray. Differential gene expression was further validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Our results demonstrated that the up-regulation of the inflammation-associated genes, ALOX5AP, S100A8 and S100A12, down-regulation of the genes related to immunity (DEFA4), metabolism (GNG11, PYGB, PRKAR2B), and growth/proliferation (HSF2, DDR2, TK1) were found in the CZ group. Furthermore, the CZ HD patients had significantly lower serum albumin levels compared with their NCZ counterparts (3.31 +/- 0.08 g/dL versus 4.18 +/- 0.12 g/dL). It appears reasonable to conclude that up-regulated inflammatory-gene expression (ALOX5AP, S100A8 and S100A12) may play an important role in CZ HD patients.

Effects of Scutellariae Radix on gene expression in HEK 293 cells using cDNA microarray.

The aim of the present study was to elucidate the molecular mechanisms underlying the anti-inflammatory effect of Scutellaria Radix (SR). The complementary DNA (cDNA) microarray method was used to survey the effects of SR on the changes of gene expression profile in HEK293 cells. Based on differential expression, 66 genes were selected for further analysis from 9,600 candidate genes in the microarray; 23 genes were validated by RT-PCR. The broad spectrum of the differentially expressed genes, including those associated with inflammation, immune response, energy metabolism, as well as others, such as ISGF3G, IL6ST, CD98, ATP5G2, PHKG2, YB-1 and SLC7A4, indicate overall cellular response to SR treatment. Our results suggest that the anti-inflammatory effect of SR may be related to IL6ST down-expression, and over-expression of CD98. Moreover, SR-related improvement in immune response may be related to the ISGF3G over-expression.

A longitudinal study of growth patterns in schoolchildren in one Taipei District. II: Sitting height, arm span, body mass index and skinfold thickness.

BACKGROUND: It has been suggested that longitudinal rather than cross-sectional growth standards be used to assess individual growth patterns. Thus, the aim of this study was to follow boys and girls throughout their pubertal years, so that a mixed longitudinal growth curve of height, weight, sitting height, arm span, skinfold thickness, body mass index (BMI), and the ratio of sitting height or arm span to stature, could be obtained. METHODS: A defined group of 1,139 healthy schoolchildren (570 boys and 569 girls) from the Shih-Pai district of Taipei were followed longitudinally for 4 years. Anthropometric measurements of height, weight, sitting height, arm span, skinfold thickness, and BMI, were obtained for each child. RESULTS: Peak sitting-height velocities of 6.1 cm/year (boys) and 6.3 cm/year (girls) were seen at 8.5 years. The second peak of sitting-height velocity occurred at a mean age of 12.5 years for boys and 11.5 years for girls. Sitting-height velocity for the whole year covering the second peak was 4.6 cm in boys and 3.2 cm in girls. Peak arm-span velocity was seen at 13.5 years for boys and 8.5 years for girls, and arm-span velocity for the whole year covering this peak was 8.4 cm/year for boys and 8.1 cm/year for girls. CONCLUSION: These data provide growth patterns for Chinese children aged 8-18 years living in a Taipei district, with percentile charts for sitting height, arm span, BMI, and skinfold thickness.

A longitudinal study of growth patterns in school children in Taipei area I: growth curve and height velocity curve.

BACKGROUND: It has been pointed out that longitudinal rather than cross-sectional growth standards should be used to assess individual linear growth. The purpose of this study is to investigate the growth characteristics of school boys and girls living in Shih-Pai district in Taipei. METHODS: A defined group of 1,139 healthy school children (570 boys and 569 girls) from the Shih-Pai district of Taipei city were followed longitudinally for 3 to 4 years. Anthropometric measurement of height and weight and physical development in each child were obtained. The annual increments were calculated every 6 months to map the peak height velocity (PHV), height velocity curve (HVC), peak weight velocity (PWV) and weight velocity curve (WVC). RESULTS: The age at peak velocity was taken as 12.5 years for boys and 10.5 years for girls, and the whole year PHV as 8.0 cm/yr in boys and 7.0 cm/yr in girls. The mean PHV was less than 1 cm in boys and girls of about 17 years and 15 years, respectively, with mean heights of 170.8 cm and 158.7 cm, respectively. CONCLUSIONS: Our preliminary results were actually calculated from the combination of longitudinal data and cross-sectional data pools. Since this is only a pilot study design, we expect that a longer follow-up period of the same cohorts would give more exact growth characteristics.