Search

Abstract Information and Communication Technologies (ICTs) can provide rich learning opportunities in classroom teaching, which requires teachers’ effective instrumental orchestrations. However, there is a lack of research regarding the development of teachers’ instrumental orchestrations. In this study, we designed and implemented a professional development course, aiming to explore whether the course could change preservice mathematics teachers’ instrumental orchestrations. To this end, an analytical framework of instrumental orchestrations within a GeoGebra environment was established. Data were collected from Chinese preservice mathematics teachers, including the videotapes of their simulated lessons, GeoGebra files, written documents, self-reflections, online speaking, etc. In the results, three participants’ changes in instrumental orchestrations were presented as main cases. It was found that the three preservice mathematics teachers’ types of instrumental orchestrations did not change, but the frequencies of those increased significantly. The changes in didactical configurations were mainly reflected in the layout of GeoGebra, and the changes in exploitation modes were mainly manifested in the techniques teachers use and the management of mathematics tasks. In addition, it was revealed that theoretical support (instrumental approach), technical support (knowledge about using GeoGebra), and community support (“Same Content Different Designs” activity and communicating and discussing with others) were useful course elements inviting changes in instrumental orchestrations. In this regard, this study contributes to providing a promising professional development course that can be used in teacher training so as to improve teachers’ instrumental orchestrations.

Crop yield losses have escalated worldwide due to extreme and/or prolonged drought periods as well as insufficient irrigation. In the cold and arid regions of northern China, the difficulty of straw decomposition is a regional problem, which is undoubtedly aggravated by the increasingly serious drought. Thus, the combination of a reasonable grain feed rotation mode and tillage mode of straw returning is an effective measure to solve this problem. This study set up a grain forage rotation (in the first year, it is used for grain production, and the straw is returned to the field after the grains are harvested; when the entire plant is harvested in the second year, it is used as feed) and two treatments for straw returning and no straw returning to the land characterized by two different water degresses (include drought stress and normal irrigation). To clarify the impact of returning straw to the field on the soil improvement and drought tolerance of various maize varieties, the effects of straw returning on the agronomic traits, hormones, osmotic adjustment substance content, whole plant fresh weight, and dry weight of six different maize varieties (MC703, A2636, DK 159, ZQ 1, 303 × 178, and ZJ 330) under drought stress were analyzed. The data showed the following: (1) After straw returning, the soil moisture content increased by 3.55–14.70% and the soil bulk density decreased by 0.73–5.23% under the drought stress treatment, and the soil physical condition became closer to the ideal value. (2) After straw returning, the plant height, ear height, stem diameter, fresh weight, and dry weight of the maize whole plant under the drought stress treatment increased by 0.95–7.70%, 4.70–15.71%, 0.31–9.33%, 2.67–36.23%, and 3.72–38.60%, respectively. (3) After straw returning, the abscisic acid, ethylene, soluble sugar, and soluble protein in the leaves under the drought stress treatment decreased by 7.92–21.42%, 8.03–3.37%, 0.63–22.98%, and 2.37–9.17%, respectively. Straw returning significantly alleviated the damage caused by drought stress to the growth and development of maize, and promoted the growth and development of maize under the drought treatment. The results of this study provide a theoretical basis for a high and stable yield of grain crops in arid areas.

Digital technologies play a key role in the digital transformation of education. In order to improve teaching effectiveness and efficiency, teachers should use digital technologies appropriately. However, some secondary school mathematics teachers have little confidence in their digital teaching behavior. This study aimed to explore the predictors of secondary school mathematics teachers' digital teaching behavior. An extended unified theory of acceptance and use of technology (UTAUT) model was adopted to predict secondary school mathematics teachers' digital teaching behavior. A questionnaire survey was conducted with all junior high school mathematics teachers in a state-level new area, which is located in a central province of China. Three hundred and eighty-five valid data were collected. The partial least squares structural equation modeling (PLS-SEM) method was used to analyze the data. It was found that technological pedagogical content knowledge (TPACK) was the biggest predictor of secondary school mathematics teachers' digital teaching behavior. Attitude, behavioral intention, performance expectancy, effort expectancy and social influence can also affect teachers' digital teaching behavior in direct and/or indirect ways. The findings have noteworthy realistic implications for enhancing digital teaching behavior of secondary school mathematics teachers and promoting digital transformation of secondary school mathematics education.

Dynamic mathematics software, such as GeoGebra, is a kind of subject-specific digital tool used for enabling users to create mathematical objects and operate them dynamically and interactively, which is very suitable for mathematics teaching and learning at all school levels, especially at the secondary school level. However, limited research has focused on how multiple influencing factors of secondary school teachers' usage behavior of dynamic mathematics software work together. Based on the unified theory of acceptance and use of technology (UTAUT) model, combined with the concept of self-efficacy, this study proposed a conceptual model used to analyze the factors influencing secondary school teachers' usage behavior of dynamic mathematics software. Valid questionnaire data were provided by 393 secondary school mathematics teachers in the Hunan province of China and analyzed using a partial least squares structural equation modeling (PLS-SEM) method. The results showed that social influence, performance expectancy and effort expectancy significantly and positively affected secondary school teachers' behavioral intentions of dynamic mathematics software, and social influence was the greatest influential factor. In the meantime, facilitating conditions, self-efficacy and behavioral intention had significant and positive effects on secondary school teachers' usage behavior of dynamic mathematics software, and facilitating conditions were the greatest influential factor. Results from the multi-group analysis indicated that gender and teaching experience did not have significant moderating effects on all relationships in the dynamic mathematics software usage conceptual model. However, major had a moderating effect on the relationship between self-efficacy and usage behavior, as well as the relationship between behavioral intention and usage behavior. In addition, training had a moderating effect on the relationship between social influence and behavioral intention. This study has made a significant contribution to the development of a conceptual model that could be used to explore how multiple factors affected secondary school teachers' usage behavior of dynamic mathematics software. It also benefits the government, schools and universities in enhancing teachers' digital teaching competencies.

Glioblastoma multiforme (GBM) is the most aggressive form of glioma and the most common primary tumor of the central nervous system. Despite significant advances in clinical management strategies and diagnostic techniques for GBM in recent years, it remains a fatal disease. The current standard of care includes surgery, radiation, and chemotherapy, but the five-year survival rate for patients is less than 5%. The search for a more precise diagnosis and earlier intervention remains a critical and urgent challenge in clinical practice. The Notch signaling pathway is a critical signaling system that has been extensively studied in the malignant progression of glioblastoma. This highly conserved signaling cascade is central to a variety of biological processes, including growth, proliferation, self-renewal, migration, apoptosis, and metabolism. In GBM, accumulating data suggest that the Notch signaling pathway is hyperactive and contributes to GBM initiation, progression, and treatment resistance. This review summarizes the biological functions and molecular mechanisms of the Notch signaling pathway in GBM, as well as some clinical advances targeting the Notch signaling pathway in cancer and glioblastoma, highlighting its potential as a focus for novel therapeutic strategies.

Abstract The formation of an academic field is evidenced by many factors, including the growth of relevant research articles and the increasing impact of highly cited publications. Building upon recent scoping reviews of journal publications in STEM education, this study aimed to provide a systematic review of high impact empirical studies in STEM education to gain insights into the development of STEM education research paradigms. Through a search of the Web of Science core database, we identified the top 100 most-cited empirical studies focusing on STEM education that were published in journals from 2000 to 2021 and examined them in terms of various aspects, including the journals where they were published, disciplinary content coverage, research topics and methods, and authorship’s nationality/region and profession. The results show that STEM education continues to gain more exposure and varied disciplinary content with an increasing number of high impact empirical studies published in journals in various STEM disciplines. High impact research articles were mainly authored by researchers in the West, especially the United States, and indicate possible “hot” topics within the broader field of STEM education. Our analysis also revealed the increased participation and contributions from researchers in diverse fields who are working to formulate research agendas in STEM education and the nature of STEM education scholarship.

Abstract Background Accurate and non-invasive diagnosis of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) can avoid unnecessary puncture and surgery. This study aimed to develop a deep learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) images to assist radiologists in identifying PDAC and CP. Methods Patients with PDAC or CP were retrospectively enrolled from three hospitals. Detailed clinicopathological data were collected for each patient. Diagnoses were confirmed pathologically using biopsy or surgery in all patients. We developed an end-to-end DLR model for diagnosing PDAC and CP using CEUS images. To verify the clinical application value of the DLR model, two rounds of reader studies were performed. Results A total of 558 patients with pancreatic lesions were enrolled and were split into the training cohort (n=351), internal validation cohort (n=109), and external validation cohorts 1 (n=50) and 2 (n=48). The DLR model achieved an area under curve (AUC) of 0.986 (95% CI 0.975–0.994), 0.978 (95% CI 0.950–0.996), 0.967 (95% CI 0.917–1.000), and 0.953 (95% CI 0.877–1.000) in the training, internal validation, and external validation cohorts 1 and 2, respectively. The sensitivity and specificity of the DLR model were higher than or comparable to the diagnoses of the five radiologists in the three validation cohorts. With the aid of the DLR model, the diagnostic sensitivity of all radiologists was further improved at the expense of a small or no decrease in specificity in the three validation cohorts. Conclusions The findings of this study suggest that our DLR model can be used as an effective tool to assist radiologists in the diagnosis of PDAC and CP.

BackgroundSevere burn injury can be a life-threatening experience and can also lead to financial issues for suffers. The purpose of the current study was to analyze the direct hospitalization costs of severe burn inpatients in Southwest China.MethodsData related to all inpatients admitted with severe burns [total body surface area (TBSA) ≥30%] pooled from 2015 to 2021 were reviewed retrospectively at the Institute of Burn Research of Army Medical University. Demographic parameters, medical economics, and clinical data were obtained from medical records.ResultsA total of 668 cases were identified. The average age was 37.49 ± 21.00 years, and 72.3% were men. The average TBSA was 51.35 ± 19.49%. The median length of stay of inpatients in the burn intensive care unit was 14 [interquartile range (IQR): 5.0–34.8] days, and the median length of stay (LOS) was 41 (IQR: 22.0–73.8) days. The mortality rate was 1.6%. The median total cost was 212,755.45 CNY (IQR: 83,908.80–551,621.57 CNY) per patient varying from 3,521.30 to 4,822,357.19 CNY. The direct cost of scald burns was dramatically lower compared with that of other types of burns, with 11,213.43 to 2,819,019.14 CNY. Medical consumables presented the largest portion of total costs, with a median cost of 65,942.64 CNY (IQR: 18,771.86–171,197.97 CNY). The crucial risk factors for medical cost in our study were TBSA, surgical frequency, LOS, depth of burn, and outcome.ConclusionWe conclude that an effective burn prevention program, shorter hospital stays, and facilitating the healing of wounds should be focused on with tailored precautionary protocols to reduce the medical costs of inpatients with severe burns.

Cross-modal remote sensing retrieval (RSCR) has an increasing importance due to the ability to quickly and flexibly retrieve valuable data from enormous remote sensing (RS) images. However, traditional RSCR methods tend to focus on the retrieval between two modalities, when the number of modalities increases, the contradiction between the increasing semantic gap and the small amount of paired data causes the model fail to learn a superior modal representation. In this paper, inspired by the visual-based modal center in RS, we construct a multi-source cross-modal retrieval network (MCRN) that manages to unify RS retrieval tasks under multiple retrieval sources. To solve the data heterogeneity caused by multiple data sources, we propose a shared pattern transfer module (SPTM) based on pattern memory and combine the theory of generative adversarial to achieve the semantic representation unbound from modality. Simultaneously, to cope with the lack of annotation data in the RS scenario, multiple unimodal self-supervised frameworks are unified to obtain robust pre-training parameters for the designed MCRN by combining domain alignment and contrastive learning. Finally, we come up with the multi-source triplet loss, the unimodal contrast loss, and the semantic consistency loss, which efficaciously make MCRN achieve competitive results through multitask learning for semantic alignment. We construct multimodal datasets M-RSICD and M-RSITMD, conduct extensive experiments and provide a complete benchmark to facilitate the development of RS multi-source cross-modal retrieval. The code of the MCRN method and the proposed dataset have been open to access at [Link].

Abstract Hydrogels are promising and widely utilized in the biomedical field. In recent years, the anti‐inflammatory function of hydrogel dressings has been significantly improved, addressing many clinical challenges presented in ongoing endeavours to promote wound healing. Wound healing is a cascaded and highly complex process, especially in chronic wounds, such as diabetic and severe burn wounds, in which adverse endogenous or exogenous factors can interfere with inflammatory regulation, leading to the disruption of the healing process. Although insufficient wound inflammation is uncommon, excessive inflammatory infiltration is an almost universal feature of chronic wounds, which impedes a histological repair of the wound in a predictable biological step and chronological order. Therefore, resolving excessive inflammation in wound healing is essential. In the past 5 years, extensive research has been conducted on hydrogel dressings to address excessive inflammation in wound healing, specifically by efficiently scavenging excessive free radicals, sequestering chemokines and promoting M1‐to‐M2 polarization of macrophages, thereby regulating inflammation and promoting wound healing. In this study, we introduced novel anti‐inflammatory hydrogel dressings and demonstrated innovative methods for their preparation and application to achieve enhanced healing. In addition, we summarize the most important properties required for wound healing and discuss our analysis of potential challenges yet to be addressed.

Melanoma is a malignant tumor that originates from melanocytes, most of which are of cutaneous origin. Most melanomas identified in the pancreas are metastatic, and primary pancreatic melanoma is extremely rare and has rarely been discussed. The correct preoperative diagnosis of pancreatic metastatic melanoma, especially primary melanoma, is challenging. Herein, we report a 43-year-old man who presented to our hospital due to unexplained left abdominal distension and pain. Abdominal ultrasound examination demonstrated multiple space-occupying lesions of the pancreas, and hypoechoic masses partially filled the splenic vein behind the pancreatic body. In the contrast-enhanced ultrasound (CEUS), all of these lesions showed iso-enhancement to slight hypo-enhancement in the arterial phase and hypo-enhancement in the venous phase. Masses in the splenic vein also showed hypo-enhancement. Imaging features suggested that the pancreatic lesions were malignant tumors. The tumor markers carcinoembryonic antigen, carbohydrate antigen 125 and carbohydrate antigen 19-9 were within normal limits. Based on clinical symptoms, imaging findings and incidence of pancreatic tumors, the patient’s clinical diagnosis was pancreatic carcinoma. Surgery was performed for the patient, while postoperative pathology confirmed malignant melanoma of the pancreas. Therefore, it is significant to identify the clinical and imaging manifestations of pancreatic melanoma in order to better manage the disease. Herein, we reported this case and reviewed the literature from 2000 to 2021 on the clinical and imaging features of 26 patients with pancreatic melanoma. It may improve clinicians’ awareness of the clinical and imaging performance of pancreatic melanoma, resulting in improved diagnosis, differential diagnosis, treatment, and outcomes.

For integrated energy systems (IES) composed of a set of energy hubs (EHs), a consensus control method is usually adopted to achieve accurate sharing of electrical and thermal composite energies. To solve the communication redundancy problem of the consensus control method, a hierarchical optimization and distributed control scheme based on a dynamic event-triggered mechanism of EHs is proposed to realize stable operation of IES. An economic optimization strategy based on equal increment principle is improved to minimize the operation costs of IES in the second layer. Due to consensus control being integrated into the supply-demand power deviation calculations of EHs, the desired electrical and thermal power trajectories are accurately determined. To improve dynamic response performances in the presence of uncertain disturbances, an event-triggered communication mechanism is designed in the primary layer. The triggering threshold can be adjusted dynamically according to changes of electrical and thermal power outputs, and the redundant communication requirement in the electrical branches is reduced. Considering the coupling characteristics of IES energy networks, a consensus control method is promoted to synchronously track the desired electric and thermal power trajectories of EHs, and the goal of accurate power sharing is achieved. The frequency and pipeline pressure fluctuations are also limited within the allowable range. The economic optimization and coordinated operation of electrical and thermal composite energies in IES are guaranteed by the proposed hierarchical control structure. Additionally, only information from neighboring EHs at the event-triggered time is involved, so the computation simplicity and control performance can be obtained simultaneously. The hardware-in-loop experimental results are conducted to demonstrate the effectiveness of the proposed control strategy.

Dynamic mathematics software, such as GeoGebra, is one of the most important teaching and learning media. This kind of software can help teachers teach mathematics, especially geometry, at the elementary school level. However, the use of dynamic mathematics software of elementary school teachers is still very limited so far. This study analyzed the factors influencing elementary school teachers’ usage behavior of dynamic mathematics software. Four independent variables, namely performance expectancy (PE), effort expectancy (EE), social influence (SI), and facilitating conditions (FC) from the united theory of acceptance and use of technology (UTAUT), were used to understand elementary school teachers’ usage behavior of dynamic mathematics software. A questionnaire survey was conducted in the Hunan and Guangdong provinces of China. Two hundred and sixty-six elementary school mathematics teachers provided valid questionnaire data. The partial least squares structural equation modeling (PLS-SEM) approach was used to analyze the data. The results showed that facilitating conditions and effort expectancy significantly affect elementary school teachers’ usage behavior of dynamic mathematics software, and facilitating conditions were the biggest factor that affected user behavior. The moderating effects of gender, major, and training on all relationships in the dynamic mathematics software usage conceptual model were not significant. This study contributes by developing a model and providing new knowledge to elementary school principals and the government about factors that can increase the adoption of dynamic mathematics software.

BackgroundAcute kidney injury (AKI) is a morbid complication and the main cause of multiple organ failure and death in severely burned patients. The objective of this study was to explore epidemiology, risk factors, and outcomes of AKI for severely burned patients.MethodsThis retrospective study was performed with prospectively collected data of severely burned patients from the Institute of Burn Research in Southwest Hospital during 2011–2017. AKI was diagnosed according to Kidney Disease Improving Global Outcomes (KDIGO) criteria (2012), and it was divided into early and late AKIs depending on its onset time (within the first 3 days or >3 days post burn). The baseline characteristics, clinical data, and outcomes of the three groups (early AKI, late AKI and non-AKI) were compared using logistic regression analysis. Mortality predictors of patients with AKI were assessed.ResultsA total of 637 adult patients were included in analysis. The incidence of AKI was 36.9% (early AKI 29.4%, late AKI 10.0%). Multiple logistic regression analysis revealed that age, gender, total burn surface area (TBSA), full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burn, and tracheotomy were independent risk factors for both early and late AKIs. However, sepsis was only an independent risk factor for late AKI. Decompression escharotomy was a protective factor for both AKIs. The mortality of patients with AKI was 32.3% (early AKI 25.7%, late AKI 56.3%), and that of patients without AKI was 2.5%. AKI was independently associated with obviously increased mortality of severely burned patients [early AKI, OR = 12.98 (6.08–27.72); late AKI, OR = 34.02 (15.69–73.75)]. Compared with patients with early AKI, patients with late AKI had higher 28-day mortality (34.9% vs. 19.4%, p = 0.007), 90-day mortality (57.1% vs. 27.4%, p

Weakly Supervised Semantic Segmentation (WSSS) with only image-level labels reduces the annotation burden and has been rapidly developed in recent years. However, current mainstream methods only employ a single image’s information to localize the target and do not account for the relationships across images. When faced with Remote Sensing (RS) images, limited to complex backgrounds and multiple categories, it is challenging to locate and differentiate between the categories of targets. As opposed to previous methods that mostly focused on single-image information, we propose CISM, a novel cross-image semantic mining WSSS framework. CISM explores cross-image semantics in multi-category RS scenes for the first time with two novel loss functions: the Common Semantic Mining (CSM) loss and the Non-common Semantic Contrastive (NSC) loss. In particular, prototype vectors and the Prototype Interactive Enhancement (PIE) module were employed to capture semantic similarity and differences across images. To overcome category confusions and closely related background interferences, we integrated the Single-Label Secondary Classification (SLSC) task and the corresponding single-label loss into our framework. Furthermore, a Multi-Category Sample Generation (MCSG) strategy was devised to balance the distribution of samples among various categories and drastically increase the diversity of images. The above designs facilitated the generation of more accurate and higher-granularity Class Activation Maps (CAMs) for each category of targets. Our approach is superior to the RS dataset based on extensive experiments and is the first WSSS framework to explore cross-image semantics in multi-category RS scenes and obtain cutting-edge state-of-the-art results on the iSAID dataset by only using image-level labels. Experiments on the PASCAL VOC2012 dataset also demonstrated the effectiveness and competitiveness of the algorithm, which pushes the mean Intersection-Over-Union (mIoU) to 67.3% and 68.5% on the validation and test sets of PASCAL VOC2012, respectively.

Remote sensing super-resolution (RSSR) aims to improve remote sensing (RS) image resolution while providing finer spatial details, which is of great significance for high-quality RS image interpretation. The traditional RSSR is based on the optimization method, which pays insufficient attention to small targets and lacks the ability of model understanding and detail supplement. To alleviate the above problems, we propose the generative Diffusion Model with Detail Complement (DMDC) for RS super-resolution. Firstly, unlike traditional optimization models with insufficient image understanding, we introduce the diffusion model as a generation model into RSSR tasks and regard low-resolution images as condition information to guide image generation. Next, considering that generative models may not be able to accurately recover specific small objects and complex scenes, we propose the detail supplement task to improve the recovery ability of DMDC. Finally, the strong diversity of the diffusion model makes it possibly inappropriate in RSSR, for this purpose, we come up with joint pixel constraint loss and denoise loss to optimize the direction of inverse diffusion. The extensive qualitative and quantitative experiments demonstrate the superiority of our method in RSSR with small and dense targets. Moreover, the results from direct transfer to different datasets also prove the superior generalization ability of DMDC.

Antimicrobial resistance (AMR) is one of the most significant threats to global public health. As antibiotic failure is increasing, phages are gradually becoming important agents in the post-antibiotic era. In this study, the therapeutic effects and safety of kpssk3, a previously isolated phage infecting carbapenem-resistant hypermucoviscous Klebsiella pneumoniae (CR-HMKP), were evaluated in a mouse model of systemic CR-HMKP infection. The therapeutic efficacy experiment showed that intraperitoneal injection with a single dose of phage kpssk3 (1 × 107 PFU/mouse) 3 h post infection protected 100% of BALB/c mice against bacteremia induced by intraperitoneal challenge with a 2 × LD100 dose of NY03, a CR-HMKP clinical isolate. In addition, mice were treated with antibiotics from three classes (polymyxin B, tigecycline, and ceftazidime/avibactam plus aztreonam), and the 7 days survival rates of the treated mice were 20, 20, and 90%, respectively. The safety test consisted of 2 parts: determining the cytotoxicity of kpssk3 and evaluating the short- and long-term impacts of phage therapy on the mouse gut microbiota. Phage kpssk3 was shown to not be cytotoxic to mammalian cells in vitro or in vivo. Fecal samples were collected from the phage-treated mice at 3 time points before (0 day) and after (3 and 10 days) phage therapy to study the change in the gut microbiome via high-throughput 16S rDNA sequence analysis, which revealed no notable alterations in the gut microbiota except for decreases in the Chao1 and ACE indexes.

Introduction Helicobacter pylori (H. pylori) is the most well-known risk factor for gastric cancer. At present, H. pylori shows varying levels of resistance to different treatments, leading to a lower rate of H. pylori eradication. The aim of this study is to evaluate the efficacy of polaprezinc-containing quadruple therapy (PQT) for the eradication of H. pylori infection and, thus, to provide more evidence to inform the clinical treatment of H. pylori infection in China.Methods and analysis This is a single-centre, single-blind, non-inferiority, randomised controlled trial, enrolling 158 patients with H. pylori infection. Patients are randomised (1:1) to the two groups for a 14-day therapy. Treatment group: PQT (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, polaprezinc 75 mg) two times per day; control group: bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, bismuth potassium citrate 220 mg) two times per day. The primary outcome is the rate of H. pylori eradication. Secondary outcomes are the incidence of adverse events and the gastrointestinal microbiota distribution. The 16S ribosomal RNA (16S rRNA) next-generation sequencing (NGS) is used to evaluate the effect of two different therapies on the distribution of the gastrointestinal microbiota.Ethics and dissemination This study was approved by the Ethics Committee of Sichuan Cancer Center & Hospital (No. SCCHEC-02-2019-015). Any amendment to the research protocol will be submitted for ethical approval. All participants must provide informed consent. On completion, the results of the study will be published in the appropriate peer-reviewed journal.Trial registration number ChiCTR1900025800; preresults.

Background: Endoscopic resection cap technique (ER-Cap), multiband mucosectomy (MBM), and endoscopic submucosal dissection (ESD) have been widely applied in the treatment of esophageal squamous neoplasia and cancer. However, little is known with regards to the comparison of these methods. This study aimed to compare the feasibility, safety, effectiveness, and costs of these three techniques. Methods: A retrospective analysis of patients with squamous premalignant or early malignant lesions of the esophagus undergoing ER-Cap, MBM, or ESD from January 2009 to December 2015 in one of the centers in China was performed. The procedural data and follow-up data for all patients were recorded. Results: A total of 672 patients with 733 lesions were included; 148 lesions (133 patients) were treated with ER-Cap, 427 lesions (388 patients) with MBM, and 158 lesions (151 patients) with ESD. The mean age was 61.59 years and the male-to-female ratio was 2.78:1. The operation time was significantly shorter for ER-Cap (29.26 ± 16.73 mins, p

Background/Aims: N-acetylcysteine (NAC) is a novel and promising agent with activity against bacterial biofilms. Human serum also inhibits biofilm formation by some bacteria. We tested whether the combination of NAC and human serum offers greater anti-biofilm activity than either agent alone. Methods: Microtiter plate assays and confocal laser scanning microscopy were used to evaluate bacterial biofilm formation in the presence of NAC and human serum. qPCR was used to examine expression of selected biofilm-associated genes. Extracellular matrix (ECM) was observed by transmission electron microscopy. The antioxidants GSH or ascorbic acid were used to replace NAC, and human transferrin, lactoferrin, or bovine serum albumin were used to replace serum proteins in biofilm formation assays. A rat central venous catheter model was developed to evaluate the effect of NAC on biofilm formation in vivo. Results: NAC and serum together increased biofilm formation by seven different bacterial strains. In Staphylococcus aureus, expression of genes for some global regulators and for genes in the ica-dependent pathway increased markedly. In Pseudomonas aeruginosa, transcription of las, the PQS quorum sensing (QS) systems, and the two-component system GacS/GacA increased significantly. ECM production by S. aureus and P. aeruginosa was also enhanced. The potentiation of biofilm formation is due mainly to interaction between NAC and transferrin. Intravenous administration of NAC increased colonization by S. aureus and P. aeruginosa on implanted catheters. Conclusions: NAC used intravenously or in the presence of blood increases bacterial biofilm formation rather than inhibits it.

Background/Aims: As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.

Background: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Results: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. Conclusions: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.

Background: Heat causes airway damage during inhalation injury because of bronchial epithelial cell damage. Accumulating evidence shows that mitochondrial uniporter (MCU) is involved in cell damage. We investigated the MCU activity after heat treatment and assessed whether Astragaloside-IV (AS-IV) suppresses heat-induced apoptosis in bronchial epithelial cells by inhibiting the activation of the mitochondrial Ca2+ uniporter (MCU), mitochondrial depolarisation and reactive oxygen species (ROS) production. Methods: The bronchial epithelial cell line 16HBE14o- was heat treated, and cell apoptosis was induced in vitro and in vivo. AS-IV was inorganically administered to Wistar rats twice a day after thermal inhalation injury, and 16HBE140- cells were treated with AS-IV after incubation at 47°C for 5 min. Protein expression was determined using Western blotting and commercial kits, apoptosis with TUNEL staining, mitochondrial channel activity by patch clamp, reactive oxygen species by MitoSOXTM fluorescence, ATP levels and enzyme activities by commercial kits as well as mitochondrial respiration and calcium by fluorescence. Results: AS-IV markedly inhibited heat-induced apoptosis, as indicated by the increased expression of the pro-apoptotic genes Bak, Bik and Bmf and increased expression of the apoptosis markers Bax, cleaved parp, cleaved caspase3 and cytochrome C. We found that MCU activation promoted mitochondrial Ca2+ overload, ATP depletion, mitochondrial ROS production and cytochrome c release and rapidly induced apoptosis. However, AS-IV treatment reduced excessive MCU activation and led to resistance against mitochondrial Ca2+ overload and excessive cytochrome C release; these effects were blocked by the MCU activator spermine. AS-IV treatment elevated ATP production and decreased ROS activity. Conclusions: MCU plays crucial roles in heat-induced mitochondrial apoptosis in 16HBE140- cells, suggesting a potential target for AS-IV treatment.

Background/Aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.

Abstract Professor Li Ao was one of the founders of Chinese burn medicine and one of the most renowned doctors and researchers of burns in China. He established one of the Chinese earliest special departments for burns at Third Military Medical University (TMMU) in 1958. To memorialize Professor Li Ao on his 100th birthday in 2017 and introduce our extensive experience, it is our honor to briefly review the development and achievement of the Chinese burn medicine from TMMU. The epidemiology and outcomes of admitted burn patients since 1958 were reviewed. Furthermore, main achievements of basic and clinical research for the past roughly 60 years were presented. These achievements mainly included the Chinese Rule of Nine, fluid resuscitation protocol, experience in inhalation injury, wound treatment strategies, prevention and treatment of burn infections, nutrition therapy, organ support therapies, and rehabilitation. The progress shaped and enriched modern Chinese burn medicine and promoted the development of world burn medicine.

Pseudomonas aeruginosa is the leading cause of infection in burn patients. The increasing carbapenem resistance of P. aeruginosa has become a serious challenge to clinicians. The present study investigated the molecular typing and carbapenem resistance mechanisms of 196 P. aeruginosa isolates from the bloodstream and wound surface of patients in our burn center over a period of 6 years. By multilocus sequence typing (MLST), a total of 58 sequence types (STs) were identified. An outbreak of ST111, a type that poses a high international risk, occurred in 2014. The isolates from wound samples of patients without bacteremia were more diverse and more susceptible to antibiotics than strains collected from the bloodstream or the wound surface of patients with bacteremia. Importantly, a large proportion of the patients with multisite infection (46.51%) were simultaneously infected by different STs in the bloodstream and wound surface. Antimicrobial susceptibility testing of these isolates revealed high levels of resistance to carbapenems, with 35.71% susceptibility to imipenem and 32.14% to meropenem. To evaluate mechanisms associated with carbapenem resistance, experiments were conducted to determine the prevalence of carbapenemase genes, detect alterations of the oprD porin gene, and measure expression of the ampC β-lactamase gene and the mexB multidrug efflux gene. The main mechanism associated with carbapenem resistance was mutational inactivation of oprD (88.65%), accompanied by overexpression of ampC (68.09%). In some cases, oprD was inactivated by insertion sequence element IS1411, which has not been found previously in P. aeruginosa. These findings may help control nosocomial P. aeruginosa infections and improve clinical practice.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are prevalent in burn wards, and are especially serious in S. aureus bacteremia (SAB) patients. Glycopeptides and daptomycin are effective against MRSA infections, but MIC creeps can reduce their efficacy. Our object was to perform a molecular epidemiological investigation of S. aureus isolates in our burn center and to evaluate MICs for antimicrobials against SAB-associated MRSA isolates. A total of 259 S. aureus isolates, obtained from August 2011 to July 2016, were used in this study. Multiple molecular typing was used for molecular epidemiological analysis. E-tests were used to determine MICs of vancomycin, teicoplanin, and daptomycin for SAB-associated MRSA isolates. MIC values were stratified by collection date or source and compared. Spearman's test was used to analyze MICs correlations amongst tested antimicrobials. ST239-MRSA-III-t030-agrI clone was found to be dominant in both SAB and non-SAB patients, and significantly more in SAB patients (P < 0.0001). SAB-MRSA isolates exhibited decreased MICs for vancomycin, teicoplanin, and daptomycin during the 5-year period. Compared to those isolated from catheters or wounds, SAB-MRSA isolates from the bloodstream were less susceptible to vancomycin and daptomycin, but more susceptible to teicoplanin. MICs Correlation was found only between vancomycin and daptomycin in MRSA isolates from the bloodstream (rho = 0.250, P = 0.024). In conclusion, our results suggest that MRSA infections are still serious problems in burn centers. In contrast to most other studies, we observed increased susceptibility to glycopeptides and daptomycin against SAB-associated MRSA in our center from 2011 to 2016, suggesting the use of glycopeptides does not lead to MIC creeps. Isolates from different sites of the body may exhibit different levels of susceptibility and change trend over time for different antimicrobials, antimicrobials selection for MRSA infections should be considered comprehensively.

The gastrointestinal microbiome is crucial in human health. With greater than 10 times the cell count of an individual, the gastrointestinal microbiome provides many benefits to the host. It plays an important role in chronic illnesses and immune diseases and also following burns and trauma. This study aimed to determine whether severe burns affect the gastrointestinal microbiome during the early stages of after burn injury and the extent to which the microbiome is disturbed by such burns. We used a rat burn model to investigate any changes occurring in the microbiome after the burn trauma using 16S rRNA sequencing and downstream α-diversity, β-diversity, and taxonomy analysis. With 128631 and 143694 clean sequence reads, an average of 2287 and 2416 operational taxonomic units (OTUs) were recognized before and after the burn injury, respectively. Bacterial diversity within the pre- and post-burn groups was similar according to OTU richness, Chao 1 index, Shannon index and ACE index. However, the constituents of the gastrointestinal microbiota changed after the burn injury. Compared with the pre-burn samples, the post-burn samples showed a tendency to cluster together. The ratio of Firmicutes to Bacteroidetes decreased after the burn injury. Also, the abundance of some probiotic organisms (i.e., butyrate-producing bacteria and Lactobacillus) decreased after the burn injury. In contrast, opportunistic pathogenic bacteria, such as those of the genera Escherichia and Shigella and the phylum of Proteobacteria are more abundant post-burn. In conclusion, dysbiosis in the gastrointestinal microbiome was observed after the burn injury. Although the total number of species in the gastrointestinal microbiome did not differ significantly between the pre- and post-burn injury groups, the abundance of some bacterial components was affected to various extents.

Staphylococcus aureus is a common pathogen isolated from burn patients that can form biofilms on burn wounds and implanted deep vein catheters, which often leads to refractory infections or even biofilm-related sepsis. As biofilm formation is usually regulated by environmental conditions, we hypothesized that serum composition may be altered after burn injury, potentially affecting the ability of infecting bacteria to form biofilms. As predicted, we observed that serum from burn-injured rats increases biofilm formation by S. aureus and also induces bacterial aggregation and adherence to human fibronectin and fibrinogen. Analysis of potential regulatory factors revealed that exposure to burn serum decreases expression of the quorum-sensing agr system and increases mRNA levels of some biofilm inducers such as sarA and icaA. In addition, we also observed that burn serum imposes oxidative stress and increases expression of key oxidoreductase genes (sodA, sodM, katA, and ahpC) in S. aureus. Importantly, the ability of burn serum to enhance biofilm formation and bacterial cell aggregation can be abrogated by treatment with an antioxidant. Taken together, these findings indicate that burn serum increases S. aureus biofilm formation via elevated oxidative stress, and may lead to novel strategies to control biofilm formation and infection in burn patients.

Mortality remains one of the most important end-point quality control parameters to evaluate a burn care system. We retrospectively reviewed the characteristics and multiple organ dysfunction syndrome (MODS) patterns of burn deaths in our center from January 2003 to December 2009. The mortality rate during this time period was 2.3%. Fifty-six patients died, including 49 males and 7 females. The mean survival time was 28.45 ± 24.60 days. The burn percentage was (76.70 ± 26.86) % total burn surface area (TBSA), with (27.74 ± 24.95) % deep-partial thickness burns and (46.88 ± 33.84) % full-thickness burns. Inhalation injury was diagnosed in 36 (64.29%) patients. Patients who had undergone an operation, particularly in the first week post-burn, had a significantly longer survival time. An average of 5.50 ± 1.35 malfunctioning organs per patient and a mean sequential organ failure assessment (SOFA) score of 13.91 ± 3.65 were observed. The most frequently malfunctioning organs were involved in the respiratory, hematologic, circulatory, and central nervous systems. Most of the organ damage occurred during the first week post-burn, followed by 4 weeks later, with relatively less organ damage observed in the third week. Among patients with a TBSA over 50%, non-survivors had larger burn sizes (particularly larger full-thickness burns) and a higher incidence of inhalation injury compared with survivors; non-survivors were also more likely to have microorganism-positive blood and sputum cultures. In conclusion, burn deaths are related to a higher burn percentage, inhalation injury, MODS, and infection. Early operation may help improve survival duration.

Intestinal epithelial cell (IEC) apoptosis induced by hypoxiacompromise intestinal epithelium barrier function. Both Akt andHsp90 have cytoprotective function. However, the specific roleof Akt and Hsp90β in IEC apoptosis induced by hypoxia has notbeen explored. We confirmed that hypoxia-induced apoptosiswas reduced by Hsp90β overexpression but enhanced bydecreasing Hsp90β expression. Hsp90β overexpressionenhanced BAD phosphorylation and thus reduced mitochondrialrelease of cytochrome C. Reducing Hsp90β expression hadopposite effects. The protective effect of Hsp90β againstapoptosis was negated by LY294002, an Akt inhibitor. Furtherstudy showed that Akt phosphorylation was enhanced byHsp90β, which was not due to the activation of upstream PI3Kand PDK1 but because of stabilization of pAkt via directinteraction between Hsp90β and pAkt. These results demonstratethat Hsp90β may play a significant role in protecting IECs fromhypoxia-induced apoptosis via stabilizing pAkt to phosphorylateBAD and reduce cytochrome C release. [BMB Reports 2013;46(1): 47-52]

Acinetobacter baumannii is a leading pathogen responsible for nosocomial infections. The emergence of carbapenem-resistant A. baumannii (CRAB) has left few effective antibiotics for clinicians to use. To investigate the temporal evolutionary relationships among CRAB strains, we collected 248 CRAB isolates from a Chinese burns institute over 3 years. The prevalence of the OXA-23 gene was detected by polymerase chain reaction. Multilocus sequence typing was used to type the CRAB strains and eBURST was used to analyze their evolutionary relationships. Wood surfaces (41%), sputa (24%), catheters (15%) and bloods (14%) were the four dominant isolation sources. Except for minocycline (33.5%) and sulbactam/cefoperazone (74.6%), these CRAB strains showed high resistance rates (> 90%) to 16 tested antibiotics. The 248 isolates fall into 26 sequence types (ST), including 9 known STs and 17 unknown STs. The majority (230/248) of these isolates belong to clonal complex 92 (CC92), including eight isolates belonging to seven unreported STs. A new clonal complex containing 11 isolates grouped into four new STs was identified. The OXA-23 gene was detected at high prevalence among the CRAB isolates and the prevalence rate among the various STs differed. The majority of the isolates displayed a close evolutionary relationship, suggesting that serious nosocomial spreading and nosocomial infections of CRAB have occurred in the burn unit. In conclusion, the main clonal complex for CRAB in this Chinese burn unit remain unchanged during the 3-year study period, and a new clonal complex was identified. CC92 is the dominant complex, and more attention should be directed towards monitoring the new clonal complex we have identified herein.