A nomogram for predicting hemorrhagic shock in pediatric patients with multiple trauma.

The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer-Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

BACKGROUND: Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. DATA SOURCES: A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". RESULTS: Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. CONCLUSIONS: Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

RDmaster: A novel phenotype-oriented dialogue system supporting differential diagnosis of rare disease.

BACKGROUND: Clinicians often lack the necessary expertise to differentially diagnose multiple underlying rare diseases (RDs) due to their complex and overlapping clinical features, leading to misdiagnoses and delayed treatments. The aim of this study is to develop a novel electronic differential diagnostic support system for RDs. METHOD: Through integrating two Bayesian diagnostic methods, a candidate list was generated with enhance clinical interpretability for the further Q&A based differential diagnosis (DDX). To achieve an efficient Q&A dialogue strategy, we introduce a novel metric named the adaptive information gain and Gini index (AIGGI) to evaluate the expected gain of interrogated phenotypes within real-time diagnostic states. RESULTS: This DDX tool called RDmaster has been implemented as a web-based platform (http://rdmaster.nbscn.org/). A diagnostic trial involving 238 published RD patients revealed that RDmaster outperformed existing RD diagnostic tools, as well as ChatGPT, and was shown to enhance the diagnostic accuracy through its Q&A system. CONCLUSIONS: The RDmaster offers an effective multi-omics differential diagnostic technique and outperforms existing tools and popular large language models, particularly enhancing differential diagnosis in collecting diagnostically beneficial phenotypes.

The epidemiological characteristics of pediatric head injury in Hangzhou, China: a retrospective study based on cranial CT examinations.

PRIMARY OBJECTIVE: This study aims to create a pediatric head injury database based on cranial CT examinations and explore their epidemiologic characteristics. METHODS: Data related to cranial CT examinations of pediatric head injuries from March 2014 to March 2021 were collected at outpatient and emergency department of a pediatric medical center. The causes of injury, observable post-injury symptoms, and cranial injury findings were extracted with the assistance of natural language processing techniques. RESULTS: Reviewing the data from records on 52,821 children with head injuries over a period of 7 years, the most common causes of pediatric head injury were falls (58.3%), traffic accidents (26.0%), smash/crush/strike (13.9%), violence (1.5%) and sports-related incidents (0.3%). Overall, most of those injured were boys which accounting for 62.2% of all cases. Skull fractures most commonly occur in the parietal bone (9.0%), followed by the occipital (5.2%), frontal (3.3%) and temporal bones (3.0%). Most intracranial hemorrhages occurred in epidural (5.8%), followed by subdural (5.1%), subarachnoid (0.9%), intraparenchymal (0.5%) and intraventricular (0.2%) hemorrhages. Spring and autumn showed more events than any other season. CONCLUSIONS: To the best of our knowledge, this is the largest sample of epidemiological study of head injury in the Chinese pediatric population to date.

Use of extracorporeal membrane oxygenation in children with burn injury: Case report and literature review.

RATIONALE: Burns are one of the most debilitating injuries in the world and one of the major causes of accidental disability and death among children. Severe burns can result in irreversible brain damage, placing patients at high risk of brain failure and high mortality. Therefore, timely diagnosis and treatment of burn encephalopathy are crucial for improving prognosis. In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used to improve the prognosis of patients with burns. Here, we report a case of ECMO treatment in a child with burns and review the relevant literature. PATIENT CONCERNS: A 7-year-old boy with a modified Baux score of 24 presented with asphyxia, loss of consciousness, refractory hypoxemia, and malignant arrhythmia after smoke inhalation for 1 day. Fiberoptic bronchoscopy revealed a large amount of black carbon-like substances aspirated from the trachea. DIAGNOSES: Considering that the boy inhaled a large amount of smoke, the clinical manifestation was unclear consciousness, laboratory examination revealed continuous low blood oxygen saturation, and bronchoscopy revealed a large amount of black carbon-like substances in the trachea, thereby leading to the diagnosis of asphyxia, inhalation pneumonia, burn encephalopathy, multiple organ dysfunction syndrome, and malignant arrhythmia. In addition, pulmonary edema and carbon monoxide poisoning are caused by chemical agents, gas fumes, and vapors. INTERVENTIONS: The boy's blood oxygen saturation and blood circulation remained unstable despite various ventilation methods and medications, thus we decided to use ECMO. After 8 days of ECMO support, the patient was successfully weaned from the machine. OUTCOMES: Under the application of ECMO, the respiratory and circulatory systems significantly improved. Nevertheless, due to the progressive brain injury caused by burns and the poor prognosis, the parents ceased all treatment and the boy passed away. LESSONS: This case report demonstrates that brain edema and herniation can arise as phenotypes of burn encephalopathy, which is a challenge to treat in children. Children with confirmed or suspected burn encephalopathy should undergo diagnostic tests completed as soon as possible to confirm the diagnosis. After receiving ECMO treatment, the respiratory and circulatory systems of the burn victims reported significantly improved. Hence, ECMO is a viable alternative for supporting patients with burns.

Mechanosensitive channel MscL induces non-apoptotic cell death and its suppression of tumor growth by ultrasound.

Mechanosensitive channel of large conductance (MscL) is the most thoroughly studied mechanosensitive channel in prokaryotes. Owing to its small molecular weight, clear mechanical gating mechanism, and nanopore forming ability upon opening, accumulating studies are implemented in regulating cell function by activating mechanosensitive channel of large conductance in mammalian cells. This study aimed to investigate the potentials of mechanosensitive channel of large conductance as a nanomedicine and a mechano-inducer in non-small cell lung cancer (NSCLC) A549 cells from the view of molecular pathways and acoustics. The stable cytoplasmic vacuolization model about NSCLC A549 cells was established via the targeted expression of modified mechanosensitive channel of large conductance channels in different subcellular organelles. Subsequent morphological changes in cellular component and expression levels of cell death markers are analyzed by confocal imaging and western blots. The permeability of mitochondrial inner membrane (MIM) exhibited a vital role in cytoplasmic vacuolization formation. Furthermore, mechanosensitive channel of large conductance channel can be activated by low intensity focused ultrasound (LIFU) in A549 cells, and the suppression of A549 tumors in vivo was achieved by LIFU with sound pressure as low as 0.053 MPa. These findings provide insights into the mechanisms underlying non-apoptotic cell death, and validate the nanochannel-based non-invasive ultrasonic strategy for cancer therapy.

A time-aware attention model for prediction of acute kidney injury after pediatric cardiac surgery.

OBJECTIVE: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery, and the early detection of AKI may allow for timely preventive or therapeutic measures. However, current AKI prediction researches pay less attention to time information among time-series clinical data and model building strategies that meet complex clinical application scenario. This study aims to develop and validate a model for predicting postoperative AKI that operates sequentially over individual time-series clinical data. MATERIALS AND METHODS: A retrospective cohort of 3386 pediatric patients extracted from PIC database was used for training, calibrating, and testing purposes. A time-aware deep learning model was developed and evaluated from 3 clinical perspectives that use different data collection windows and prediction windows to answer different AKI prediction questions encountered in clinical practice. We compared our model with existing state-of-the-art models from 3 clinical perspectives using the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision-recall curve (PR AUC). RESULTS: Our proposed model significantly outperformed the existing state-of-the-art models with an improved average performance for any AKI prediction from the 3 evaluation perspectives. This model predicted 91% of all AKI episodes using data collected at 24 h after surgery, resulting in a ROC AUC of 0.908 and a PR AUC of 0.898. On average, our model predicted 83% of all AKI episodes that occurred within the different time windows in the 3 evaluation perspectives. The calibration performance of the proposed model was substantially higher than the existing state-of-the-art models. CONCLUSIONS: This study showed that a deep learning model can accurately predict postoperative AKI using perioperative time-series data. It has the potential to be integrated into real-time clinical decision support systems to support postoperative care planning.

Epidemiology of unintentional injury in children admitted to ICU in China mainland: a multi-center cross-sectional study.

Background: To investigate the epidemiology of unintentional injury in children admitted to Intensive Care Unit (ICU) in China mainland. Methods: A total of 39 hospitals in 19 provinces contributed to the 1-day point prevalence study of serious unintentional injury in children aged 0-16 years admitted to ICU. Results: A total of 1,017 patients from the 39 participating ICUs on the study day were included. Among them, 56 pediatric patients were identified to be suffered from unintentional injury from 18 participating ICUs, accounting for 5.5% (56/1,017) of all the ICU patients. The percentage of boys was more than twice the percentage of girls. Most patients had an age of less than 6 years old (n=42, 75%). The leading cause of unintentional injury was fall (n=17, 30.4%). The patterns of unintentional injury in children were age-related. There were no urban-rural differences in our cohort. The injury happened on 12:00-18:00 PM in 27 cases (48.2%), and 28 patients (50%) had injuries happened at working day. 35 patients (62.5%) received primary treatment at local hospitals. Thirty-five patients (62.5%) needed resuscitation in the emergency department, 15 patients (26.8%) still needed resuscitation in ICU. These 56 children suffered from a total of 106 lesions corresponding to 1.89 lesions per patient. Respiratory failure was most commonly seen (n=18, 32.1%). There was no death in our cohort during the study. After effective treatment during their ICU stay, 45 (80.4%) patients showed improvement, with Glasgow Coma Scale (GCS), Pediatric Trauma Score (PTS) and Pediatric Risk of Mortality III (PRISM III) score significantly better than those before treatment (P<0.05). Conclusions: Higher injury rates among children under 6 years old of age illustrate the need for preventive measures, especially programs and public policies targeting this high-risk group.

Altered T-Cell Receptor ß-Chain and Lactate Dehydrogenase Are Associated With the Immune Pathogenesis of Biliary Atresia.

Background: Biliary atresia (BA) is considered to be an autoimmune-mediating inflammatory injury. The pathogenesis of BA has been proposed with the clonal transformation of T cells expressing analogous T-cell receptor ß-chain variable regions (TRBVs). Methods: The TRBV profile of the peripheral blood mononuclear cells (PBMCs) in infants with BA and control infants (healthy donors, HDs), respectively, were characterized by using high-throughput sequencing (HTS). The diversity of T cells was analyzed based on the frequency of complementarity-determining region 3 (CDR3) or V(CDR3)J. Moreover, the correlation between absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) or diversity (clonality) indices, respectively, were analyzed for subjects with BA and HD. Results: The diversity indices of CDR3, V(CDR3)J in BA are lower than those in subjects with HD, in addition, there are significantly different levels of neutrophile, neutrophile/lymphocyte ratio (NLR), and LDH between groups of BA and HD. The correlation between ALC and diversity index is significant in subjects with HD but is not for subjects with BA. Conversely, the relationship between ALC and LDH is significant in subjects with BA but is not for subjects with HD. Moreover, 12 CDR3 motifs are deficient or lower expression in BA compared with that in the HD group. Conclusion: Our results demonstrate that the profile of TRBV repertoire is significantly different between subjects with BA and HD, and suggest that the immune imbalance and elevated LDH level are associated with the pathogenesis of BA. Moreover, the values of neutrophile, NLR, and LDH could be used for the differential diagnosis of BA.

Hypertonic saline and mannitol in patients with traumatic brain injury: A systematic and meta-analysis.

BACKGROUND: To compare the effects of 3% hypertonic saline solution and 20% mannitol solution on intracranial hypertension. METHODS: WAN-FANGDATA, CNKI, and CQVIP databases were searched, and relevant literatures of randomized controlled trials comparing 3% hypertonic saline solution with mannitol in reducing intracranial hypertension from 2010 to October 2019 were collected. Meta-analysis was performed using RevMan software. RESULTS: As a result, 10 articles that met the inclusion criteria were finally included. A total of 544 patients were enrolled in the study, 270 in the hypertonic saline group and 274 in the mannitol group. There was no significant difference in the decrease of intracranial pressure and the onset time of drug between the 2 groups after intervention (all P > .05). There was a statistically significant difference between the hypertonic saline group and the mannitol group in terms of duration of effect in reducing intracranial pressure (95% confidence interval: 0.64-1.05, Z = 8.09, P < .00001) and cerebral perfusion pressure after intervention (95% confidence interval: 0.15-0.92, Z = 2.72, P = .007). CONCLUSION: Both 3% hypertonic saline and mannitol can effectively reduce intracranial pressure, but 3% hypertonic saline has a more sustained effect on intracranial pressure and can effectively increase cerebral perfusion pressure.

Polymyxin for the treatment of intracranial infections of extensively drug-resistant bacteria in children after neurosurgical operation.

BACKGROUND: Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children. METHODS: We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≥ 3 days. RESULTS: Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed. CONCLUSIONS: Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.

Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage.

Magnetic field (MF) is being used in antitumor treatment; however, the underlying biological mechanisms remain unclear. In this study, the potency and mechanism of a previously published tumor suppressing MF exposure protocol were further investigated. This protocol, characterized as a 50 Hz electromagnetic field modulated by static MF with time-average intensity of 5.1 mT, when applied for 2 h daily for over 3 consecutive days, selectively inhibited the growth of a broad spectrum of tumor cell lines including lung cancer, gastric cancer, pancreatic cancer and nephroblastoma. The level of intracellular reactive oxygen species (ROS) increased shortly after field exposure and persisted. Subsequently, pronounced DNA damage and activation of DNA repair pathways were identified both in vitro and in vivo. Furthermore, use of free radical scavenger alleviated DNA damage and partially reduced cell death. Finally, this field was found to inhibit cell proliferation, and simultaneously induced two types of programmed cell death, apoptosis and ferroptosis. In conclusion, this tumor suppressing MF could determine cell fate through ROS-induced DNA damage, inducing oxidative stress and activation of the DNA damage repair pathways, eventually lead to apoptosis and ferroptosis, as well as inhibition of tumor growth.

PIC, a paediatric-specific intensive care database.

PIC (Paediatric Intensive Care) is a large paediatric-specific, single-centre, bilingual database comprising information relating to children admitted to critical care units at a large children's hospital in China. The database is deidentified and includes vital sign measurements, medications, laboratory measurements, fluid balance, diagnostic codes, length of hospital stays, survival data, and more. The data are publicly available after registration, which includes completion of a training course on research with human subjects and signing of a data use agreement mandating responsible handling of the data and adherence to the principle of collaborative research. Although the PIC can be considered an extension of the widely used MIMIC (Medical Information Mart for Intensive Care) database in the field of paediatric critical care, it has many unique characteristics and can support database-based academic and industrial applications such as machine learning algorithms, clinical decision support tools, quality improvement initiatives, and international data sharing.

Integrin α5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.

The tumorigenesis of colorectal cancer (CRC) is a complicated process, involving interactions between cancer cells and the microenvironment. The role of α5 integrin subunit in CRC remains controversial, and previous studies mainly focused on cancer cells. Herein, we report an important role of α5 in stroma fibroblasts in the tumorigenesis of CRC. The expression of α5 was found to be located in colorectal tumor stroma rather than in epithelia cancer cells. Immunofluorescence colocalization and gene correlation analysis confirmed that α5 was mainly expressed in cancer-associated fibroblasts (CAFs). Moreover, experimental evidence showed that α5 expression was required for the tumor-promoting effect of fibroblast cells. In an in vivo xenograft nude mice model, α5 depletion in fibroblasts dramatically suppressed fibroblast-induced tumor growth. In an in vitro cell coculture assay, α5 depletion or knockdown reduced the ability of fibroblasts to promote cancer cell migration and invasion compared with wild-type fibroblasts; moreover, we observed that the expression and assembly of fibronectin were downregulated after α5 depletion or knockdown in fibroblasts. Analysis of the RNA-Seq data of the Cancer Genome Atlas cohort revealed that high expression of ITGA5 (α5 integrin subunit) was correlated with poor overall survival in colorectal adenocarcinoma, which was further confirmed by immunohistochemistry in an independent cohort of 355 patients. Thus, our study identifies α5 integrin subunit as a novel stroma molecular marker for colorectal adenocarcinoma, offers a fresh insight into colorectal adenocarcinoma progression, and shows that α5 expression in stroma fibroblasts underlies its ability to promote the tumorigenesis of colorectal adenocarcinoma.

Tigecycline salvage therapy for critically ill children with multidrug-resistant/extensively drug-resistant infections after surgery.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of salvage therapy of tigecycline in critically ill children with infections caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) bacteria after surgery. METHODS: A retrospective chart review was performed of critically ill children after surgery who had received tigecycline for ≥3days between June 2012 and May 2016 in the surgical intensive care unit of a tertiary level children's hospital. RESULTS: Of 6442 consecutive children admitted after surgery, a total of 22 were enrolled. They had a median age of 7.5 months (interquartile range (IQR), 6 months to 4 years) and a median weight of 7.3kg (IQR, 5.1-12.5kg). Patients received tigecycline for a median 17days (IQR, 12-20 days). The median intensive care unit stay was 56days (IQR, 38-61 days) and median hospital stay was 78days (IQR, 61-94 days). Tigecycline was prescribed as culture-directed therapy in 91% of patients and as empirical therapy in 9%. Clinical success was reported in 86% of the patients. The all-cause mortality in this cohort was 18%. No serious adverse effects of tigecycline were detected in these patients. CONCLUSIONS: Tigecycline salvage therapy was successful in 86% of critically ill pediatric patients with MDR/XDR infections after surgery, with no severe adverse effects.

Well-defined and biocompatible hydrogels with toughening and reversible photoresponsive properties.

In the present study, novel hydrogels with extremely high strength, reversible photoresponsive and excellent biocompatible properties were prepared. The functional hydrogels were synthesized from a well-defined poly (ethylene glycol) polymer with spiropyran groups at a given position (PEG-SP) via a Cu(i)-catalyst Azide-Alkyne Cycloaddition (CuAAC) reaction. The molecular structures of the sequential intermediates for PEG-SP hydrogel preparation were verified by (1)HNMR and FT-IR. The mechanical property, swelling ratio, compression strength, surface hydrophilicity, and biocompatibility of the resulting hydrogel were characterized. Since spiropyran is pivotal to the switch in hydrophilicity on the hydrogel surface, the swelling ratio of PEG-SP hydrogel under Vis irradiation has a major decrease (155%). Before and after UV light irradiation, the contact angle of the hydrogel has a change of 13.8°. The photoresponsive property of this hydrogel was thus demonstrated, and such a property was also shown to be reversible. The well-defined PEG-SP hydrogel can also sustain a compressive stress of 49.8 MPa without any macro- or micro-damage, indicating its outstanding mechanical performance. Furthermore, it possessed excellent biocompatibility as demonstrated by its performance in an in vivo porcine subcutaneous implantation environment. No inflammation was observed and it got along well with the adjacent tissue. The above features indicate that PEG-SP hydrogels are promising as an implantable matrix for potential applications in biomaterial.

High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy.

BACKGROUND: Pulmonary hypertension (PH) is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Endothelial progenitor cells (EPCs) have been proved to be a potential therapeutic strategy to treat PH. Autophagy has been found to be protective to hypoxia-induced PH. In this study, we applied high shear stress (HSS)-induced PH, and examined whether EPCs confer resistance against HSS-induced PH through autophagy. METHODS: Pulmonary microvascular endothelial cells (PMVECs) were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition. Levels of p62, a selective autophagy substrate, were quantified by western blotting. Cell viability was determined by trypan blue exclusion test. RESULTS: The p62 level in PMVECs was increased at 4 hours after HSS, peaked at 12 hours and declined at 24 hours. The cell viability gradually decreased. Compared with PMVECs cultured by empty medium, in cells cultured by EPC-conditioned medium (EPC-CM), the cell viability was significantly higher; however, p62 levels were also significantly higher, suggesting inhibition of autophagy by EPC-CM. Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH. CONCLUSIONS: EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH. However, suppression of autophagy leads to cell death. EPCs could fight against PH through cellular or molecular pathways independent of autophagy. But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.