Phototherapy: a new risk factor for necrotizing enterocolitis in very low birth weight preterm infants? a retrospective case-control study.

OBJECTIVE: To investigate the association between phototherapy (PT) and the development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective case-control study was conducted on VLBW infants with or without NEC (stage IIA or greater) born at ≤35 weeks' gestation in a tertiary hospital over 7 years. Sample size calculation, trend test, as well as univariate and multiple logistic regression analyses were employed. RESULTS: A total of 824 VLBW infants were reviewed, with 74 cases and 122 controls finally enrolled. The odds of NEC increased with the duration and number of PT sessions. Exposure to >120 h and >4 instances of PT were significantly associated with NEC in multivariate analysis. CONCLUSION: This is the first study suggesting a potential association between PT and development of NEC in VLBW infants. This association needs further exploration.

Dual-Responsive Turn-On T1 Imaging-Guided Mild Photothermia for Precise Apoptotic Cancer Therapy.

Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, a dual-stimulation activated turn-on T1 imaging-based nanoparticulate system (DAS) is developed for mild photothermia (≈43 °C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticles, Fe3 O4 NPs) and a paramagnetic enhancer (Gd-DOTA complexes) are connected via the N6-methyladenine (m6 A)-caged, Zn2+ -dependent DNAzyme molecular device. The substrate strand of the DNAzyme contains one segment of Gd-DOTA complex-labeled sequence and another one of HSP70 antisense oligonucleotide. When the DAS is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled oligonucleotides. The restored T1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterward, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy.

Mitochondria spatially and temporally modulate VSMC phenotypes via interacting with cytoskeleton in cardiovascular diseases.

Cardiovascular diseases caused by atherosclerosis (AS) seriously endanger human health, which is closely related to vascular smooth muscle cell (VSMC) phenotypes. VSMC phenotypic transformation is marked by the alteration of phenotypic marker expression and cellular behaviour. Intriguingly, the mitochondrial metabolism and dynamics altered during VSMC phenotypic transformation. Firstly, this review combs VSMC mitochondrial metabolism in three aspects: mitochondrial ROS generation, mutated mitochondrial DNA (mtDNA) and calcium metabolism respectively. Secondly, we summarized the role of mitochondrial dynamics in regulating VSMC phenotypes. We further emphasized the association between mitochondria and cytoskelton via presenting cytoskeletal support during mitochondrial dynamics process, and discussed its impact on their respective dynamics. Finally, considering that both mitochondria and cytoskeleton are mechano-sensitive organelles, we demonstrated their direct and indirect interaction under extracellular mechanical stimuli through several mechano-sensitive signaling pathways. We additionally discussed related researches in other cell types in order to inspire deeper thinking and reasonable speculation of potential regulatory mechanism in VSMC phenotypic transformation.

DNA strand displacement based computational systems and their applications.

DNA computing has become the focus of computing research due to its excellent parallel processing capability, data storage capacity, and low energy consumption characteristics. DNA computational units can be precisely programmed through the sequence specificity and base pair principle. Then, computational units can be cascaded and integrated to form large DNA computing systems. Among them, DNA strand displacement (DSD) is the simplest but most efficient method for constructing DNA computing systems. The inputs and outputs of DSD are signal strands that can be transferred to the next unit. DSD has been used to construct logic gates, integrated circuits, artificial neural networks, etc. This review introduced the recent development of DSD-based computational systems and their applications. Some DSD-related tools and issues are also discussed.

Pin1/YAP pathway mediates matrix stiffness-induced epithelial-mesenchymal transition driving cervical cancer metastasis via a non-Hippo mechanism.

Cervical cancer metastasis is an important cause of death in cervical cancer. Previous studies have shown that epithelial-mesenchymal transition (EMT) of tumors promotes its invasive and metastatic capacity. Alterations in the extracellular matrix (ECM) and mechanical signaling are closely associated with cancer cell metastasis. However, it is unclear how matrix stiffness as an independent cue triggers EMT and promotes cervical cancer metastasis. Using collagen-coated polyacrylamide hydrogel models and animal models, we investigated the effect of matrix stiffness on EMT and metastasis in cervical cancer. Our data showed that high matrix stiffness promotes EMT and migration of cervical cancer hela cell lines in vitro and in vivo. Notably, we found that matrix stiffness regulates yes-associated protein (YAP) activity via PPIase non-mitotic a-interaction 1 (Pin1) with a non-Hippo mechanism. These data indicate that matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer through the Pin1/YAP pathway, and this study deepens our understanding of cervical cancer biomechanics and may provide new ideas for the treatment of cervical cancer.

A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors.

Telomerase has long been considered as a biomarker for cancer diagnosis and a therapeutic target for drug discovery. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. In this study, using the principle of distance-dependent magnetic resonance tuning, we constructed a telomerase-activated magnetic resonance imaging probe (TAMP) by connecting superparamagnetic ferroferric oxide nanoparticles (SPFONs) and paramagnetic Gd-DOTA (Gd(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexes via telomerase-responsive DNA motifs. Upon telomerase-catalyzed extension of the primer in TAMP, Gd-DOTA-conjugated oligonucleotides can be liberated from the surface of SPFONs through a DNA strand displacement reaction, restoring the T1 signal of the Gd-DOTA for a direct readout of the telomerase activity. Here we show that, by tracking telomerase activity, this probe provides consistent monitoring of tumor growth kinetics during progression and in response to drug treatment and enables in situ screening of telomerase inhibitors in whole-animal models. This study provides an alternative toolkit for cancer diagnosis, treatment response assessment, and anticancer drug screening.

Is intravenous immunoglobulin a risk factor for necrotizing enterocolitis in neonates with haemolytic disease of the newborn? A retrospective cohort study.

BACKGROUND AND OBJECTIVES: To assess whether the use of intravenous immunoglobulin (IVIG) in late-preterm and term newborns with haemolytic disease of the newborn (HDN) is associated with an increased risk of necrotizing enterocolitis (NEC). MATERIALS AND METHODS: A retrospective cohort study was conducted in a tertiary centre. Infants with HDN during early neonatal period (<7 days) who were of ≥34 weeks' gestation and born between January 2019 and October 2021 were included. Propensity score, interaction as well as univariate and multiple logistic regression analyses were employed. RESULTS: One-thousand two-hundred and fifty-nine infants with HDN were enrolled, of whom 192 (15.3%) received IVIG. NEC was diagnosed in 29 (2.3%) patients with 5 (2.6%) in the IVIG group and 24 (2.2%) in the non-IVIG group. No significant association between IVIG administration and confirmed NEC was observed using univariate analysis (p > 0.05). The possible predictors of NEC, as assessed by multivariate analysis, were caesarean delivery, haemoglobin on admission <130 g/L and patent ductus arteriosus (PDA). There was no interactive effect of IVIG against NEC for prematurity, low birth weight, caesarean delivery, haemoglobin on admission <130 g/L and PDA. CONCLUSIONS: In late-preterm and term infants with HDN, there was no evidence that the early use of IVIG led to the development of NEC.

The interactions of chelate-based ionic liquids: from the perspective of vaporization enthalpy.

The vaporization enthalpies of [CnTPP][Cu(F6-acac)3] (n = 14, 16) and [Cnmim][Cu(F6-acac)3] (n = 8, 10), a new type of chelate-based ionic liquids (ChILs), were measured by thermogravimetric analysis (ΔglHom(Tav) = 73.2-83.7 kJ mol-1), which decreased compared to their non-chelate counterparts (difference up to 34.1 kJ mol-1). This can be explained by the fact that the increase in the polar region size by chelate ions mainly leads to the decrease in Coulomb forces based on the micro-biphasic separation in ionic liquids. Vaporization enthalpies at experimental temperatures were adjusted to a reference temperature by the Verevkin's method, and compared with the data calculated by the Kabo's method, which illustrated clear differences on ChILs. In addition, some physicochemical properties of [CnTPP][Cu(F6-acac)3] (n = 14, 16) were measured including density, viscosity, conductivity, and surface tension.

Individualized dynamic PEEP (dynPEEP) vs. positive pressure ventilation in delivery room management: A retrospective cohort study.

Objective: Although nasal continuous positive airway pressure (nCPAP) is recommended in delivery room (DR) management for preterm infants, the effect of delivering nCPAP at 6-8 cmH2O is not satisfactory. Therefore, we conducted this retrospective cohort study to compare the effects of individualized dynamic positive end-expiratory pressure (dynPEEP) vs. positive pressure ventilation (PPV) in the DR on clinical outcomes. Methods: Preterm infants with a gestational age (GA) less than 30 weeks who received PPV (peak inspiratory pressure, PIP/PEEP 15-25/6-8 cmH2O) from August 2018 to July 2020 were included as Cohort 1 (PPV group, n = 55), and those who received dynPEEP (nCPAP 8-15 cmH2O) from June 2020 to April 2022 were included as Cohort 2 (dynPEEP group, n = 62). Primary outcomes included the DR intubation rate and the bronchopulmonary dysplasia (BPD) rate. The secondary outcomes included DR stabilization, transfer, admission, respiratory function, and other outcomes. Results: The percentage of singleton infants was higher in the PPV group (63.6%) than in the dynPEEP group (22.6%, p = 0.000). The DR intubation and chest compression rates were higher in the PPV group (80.0% and 18.2%, respectively) than in the dynPEEP group (45.2%, p = 0.000; 3.0%, p = 0.008, respectively). The percentage of patients with 5-min Apgar scores < 5 was higher in the PPV group (9.1%) than in the dynPEEP group (0%, p = 0.016). The partial pressure of carbon dioxide was lower in the PPV group (49.77 ± 11.28) than in the dynPEEP group (56.44 ± 13.17, p = 0.004), and lactate levels were higher in the PPV group (3.60 (2.10, 5.90)) than in the dynPEEP group (2.25 (1.38, 3.33), p = 0.002). No significant differences in the BPD rate or other secondary outcomes were noted. Conclusions: In this retrospective cohort study, the dynPEEP strategy reduced the need for DR intubation compared with PPV. The dynPEEP strategy is feasible and potentially represents an alternative respiratory strategy to PPV. Nevertheless, a randomized control trial is needed to evaluate the dynPEEP strategy.

A very preterm infant born to mother of mirror syndrome secondary to fetomaternal hemorrhage: a case report.

BACKGROUND: Mirror syndrome (MS) is defined as maternal edema with fetal hydrops and placental edema with different etiologies, such as rhesus isoimmunization and twin-twin transfusion syndrome. Herein, we showcased a unique MS case secondary to fetomaternal hemorrhage (FMH). CASE PRESENTATION: A 32-year-old gravida 2 para 0 woman diagnosed with fetal hydrops was admitted to our hospital. Maternal laboratory tests revealed anemia, slightly increased creatinine and uric acid levels, hypoproteinemia, and significantly increased alpha-fetoprotein and hemoglobin-F levels. Therefore, FMH was diagnosed initially. Two days after admission, the woman had unexpectedly progressive anasarca and started to feel chest distress, palpitations, lethargy, and oliguria, and MS was suspected. An emergency cesarean section was performed to terminate the pregnancy. The maternal clinical symptoms and laboratory tests rapidly improved after delivery. A very preterm infant with a 2080-g birthweight at 31 weeks gestation survived after emergency cesarean section, active resuscitation, emergency blood transfusion, abdominocentesis, and advanced life support. CONCLUSIONS: FMH could develop into MS, providing new insights into the etiology of MS. Once MS is diagnosed, emergency cesarean section might be an alternative treatment. The very preterm infant survived with a favorable long-term outcome, and a well-trained perinatal work team is needed for such cases.

Unpaired Person Image Generation With Semantic Parsing Transformation.

In this paper, we tackle the problem of pose-guided person image generation with unpaired data, which is a challenging problem due to non-rigid spatial deformation. Instead of learning a fixed mapping directly between human bodies as previous methods, we propose a new pathway to decompose a single fixed mapping into two subtasks, namely, semantic parsing transformation and appearance generation. First, to simplify the learning for non-rigid deformation, a semantic generative network is developed to transform semantic parsing maps between different poses. Second, guided by semantic parsing maps, we render the foreground and background image, respectively. A foreground generative network learns to synthesize semantic-aware textures, and another background generative network learns to predict missing background regions caused by pose changes. Third, we enable pseudo-label training with unpaired data, and demonstrate that end-to-end training of the overall network further refines the semantic map prediction and final results accordingly. Moreover, our method is generalizable to other person image generation tasks defined on semantic maps, e.g., clothing texture transfer, controlled image manipulation, and virtual try-on. Experimental results on DeepFashion and Market-1501 datasets demonstrate the superiority of our method, especially in keeping better body shapes and clothing attributes, as well as rendering structure-coherent backgrounds.

Modality Compensation Network: Cross-Modal Adaptation for Action Recognition.

With the prevalence of RGB-D cameras, multimodal video data have become more available for human action recognition. One main challenge for this task lies in how to effectively leverage their complementary information. In this work, we propose a Modality Compensation Network (MCN) to explore the relationships of different modalities, and boost the representations for human action recognition. We regard RGB/ optical flow videos as source modalities, skeletons as auxiliary modality. Our goal is to extract more discriminative features from source modalities, with the help of auxiliary modality. Built on deep Convolutional Neural Networks (CNN) and Long Short Term Memory (LSTM) networks, our model bridges data from source and auxiliary modalities by a modality adaptation block to achieve adaptive representation learning, that the network learns to compensate for the loss of skeletons at test time and even at training time. We explore multiple adaptation schemes to narrow the distance between source and auxiliary modal distributions from different levels, according to the alignment of source and auxiliary data in training. In addition, skeletons are only required in the training phase. Our model is able to improve the recognition performance with source data when testing. Experimental results reveal that MCN outperforms stateof- the-art approaches on four widely-used action recognition benchmarks.

Spatio-Temporal Attention-Based LSTM Networks for 3D Action Recognition and Detection.

Human action analytics has attracted a lot of attention for decades in computer vision. It is important to extract discriminative spatio-temporal features to model the spatial and temporal evolutions of different actions. In this paper, we propose a spatial and temporal attention model to explore the spatial and temporal discriminative features for human action recognition and detection from skeleton data. We build our networks based on the recurrent neural networks with long short-term memory units. The learned model is capable of selectively focusing on discriminative joints of skeletons within each input frame and paying different levels of attention to the outputs of different frames. To ensure effective training of the network for action recognition, we propose a regularized cross-entropy loss to drive the learning process and develop a joint training strategy accordingly. Moreover, based on temporal attention, we develop a method to generate the action temporal proposals for action detection. We evaluate the proposed method on the SBU Kinect Interaction data set, the NTU RGB + D data set, and the PKU-MMD data set, respectively. Experiment results demonstrate the effectiveness of our proposed model on both action recognition and action detection.

Unconjugated bilirubin induces pyroptosis in cultured rat cortical astrocytes.

BACKGROUND: Bilirubin-induced neurological dysfunction (BIND), a severe complication of extreme neonatal hyperbilirubinemia, could develop into permanent neurodevelopmental impairments. Several studies have demonstrated that inflammation and nerve cell death play important roles in bilirubin-induced neurotoxicity; however, the underlying mechanism remains unidentified. METHODS: The present study was intended to investigate whether pyroptosis, a highly inflammatory form of programmed cell death, participated in the bilirubin-mediated toxicity on cultured rat cortical astrocytes. Further, VX-765, a potent and selective competitive drug, was used to inhibit the activation of caspase-1. The effects of VX-765 on astrocytes treated with bilirubin, including the cell viability, morphological changes of the cell membrane and nucleus, and the production of pro-inflammation cytokines, were observed. RESULTS: Stimulation of the astrocytes with unconjugated bilirubin (UCB) at the conditions mimicking those of jaundiced newborns significantly increased the activation of caspase-1. Further, caspase-1 activation was inhibited by treatment with VX-765. Compared with UCB-treated astrocytes, the relative cell viability of VX-765-pretreated astrocytes was improved; meanwhile, the formation of plasma membrane pores was prevented, as measured by lactate dehydrogenase release, trypan blue staining, and ethidium bromide (EtBr) uptake. Moreover, DNA fragmentation was partly attenuated and the release of IL-1ß and IL-18 was apparently decreased. CONCLUSION: Pyroptosis is involved in the process of UCB-induced rat cortical astrocytes' injury in vitro and may be the missing link of cell death and inflammatory response exacerbating UCB-related neurotoxicity. More importantly, the depression of caspase-1 activation, the core link of pyroptosis, attenuated UCB-induced cellular dysfunction and cytokine release, which might shed light on a new therapeutic approach to BIND.

Microbial investigations in throat swab and tracheal aspirate specimens are beneficial to predict the corresponding endotracheal tube biofilm flora among intubated neonates with ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in neonatal intensive care units with high morbidity and mortality. Bacterial biofilm in the endotracheal tube (ET) provides a notable and persistent source of pathogens that may cause VAP, and thus is important for VAP detection. However, during intubation microbial investigations in ET, samples are unavailable due to the infeasibility of collecting ET samples during intubation of neonates. It is therefore of great importance to find alternative sources of samples that can help identify the ET biofilm flora. In the present study, the microbial signatures of throat swabs and tracheal aspirates were compared with ET biofilm samples from VAP neonates using 16S ribosomal RNA gene polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), cloning and sequencing. Sequences were assigned to phylogenetic species using BLAST. Microbial diversity and richness among the three types of specimens were compared based on their DGGE fingerprints, and taxonomic characteristics based on the BLAST results. The microbial richness and diversity of ET biofilms were similar to tracheal aspirate yet significantly different from throat swab samples (P<0.05). Compared with ET biofilms, the overall constituent ratio of microflora was significantly different in throat swab and tracheal aspirate samples (P<0.05). However tracheal aspirate samples were useful for predicting Staphylococcus sp. in ET biofilms with a sensitivity of 85.7% and a specificity of 83.3%. The sensitivity for the combination of tracheal aspirate and throat swab samples to detect Staphylococcus sp. in ET biofilms was 100%. The detection of Pseudomonas sp. in throat swabs assisted its identification in ET biofilms (sensitivity 33.3% and specificity 100%). The results of the present study suggest that microbial investigations in throat swab and tracheal aspirate samples are beneficial for identifying the ET biofilm flora. There may therefore be clinical applications of using substituent samples to identify pathogens in ET biofilms for VAP surveillance among intubated neonates.

Streptococcus sp. in neonatal endotracheal tube biofilms is associated with ventilator-associated pneumonia and enhanced biofilm formation of Pseudomonas aeruginosa PAO1.

Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation leading to high morbidity and mortality among intubated neonates in neonatal intensive care units (NICUs). Endotracheal tube (ETT) biofilm flora were considered to be responsible for the occurrence of VAP as a reservoir of pathogens. However, regarding neonates with VAP, little is known about the complex microbial signatures in ETT biofilms. In the present study, a culture-independent approach based on next generation sequencing was performed as an initial survey to investigate the microbial communities in ETT biofilms of 49 intubated neonates with and without VAP. Our results revealed a far more complex microflora in ETT biofilms from intubated neonates compared to a previous culture-based study. The abundance of Streptococci in ETT biofilms was significantly related to the onset of VAP. By isolating Streptococci in ETT biofilms, we found that Streptococci enhanced biofilm formation of the common nosocomial pathogen Pseudomonas aeruginosa PAO1 and decreased IL-8 expression of airway epithelia cells exposed to the biofilm conditioned medium of PAO1. This study provides new insight into the pathogenesis of VAP among intubated neonates. More studies focusing on intubated neonates are warranted to develop strategies to address this important nosocomial disease in NICUs.

Cardiac Protection of Valsartan on Juvenile Rats with Heart Failure by Inhibiting Activity of CaMKII via Attenuating Phosphorylation.

Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan (Sham + Val) or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups. Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration. Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281.

The Blockade of NF-κB Activation by a Specific Inhibitory Peptide Has a Strong Neuroprotective Role in a Sprague-Dawley Rat Kernicterus Model.

Kernicterus, the permanent nerve damage occurring as a result of bilirubin precipitation, still occurs worldwide and may lead to death or permanent neurological impairments. However, the underlying mechanisms remain unclear, and effective therapeutic strategies are lacking. The present study aims to investigate the activation of NF-κB and to identify the effect of NF-κB inhibition on the newborn rat kernicterus model. The NF-κB essential modifier-binding domain peptide (NBD), coupled with the HIV trans-activator of transcription peptide (TAT) was used to inhibit NF-κB. NF-κB was significantly activated in the cerebrum at 1 and 3 h (p < 0.05) after the model was established, as measured by EMSA. NF-κB activation was inhibited by intraperitoneal administration of TAT-NBD. The general conditions of the TAT-NBD-treated rats were improved; meanwhile, these rats performed much better on the neurological evaluation, the rotarod test, and the Morris water maze test (p < 0.05) than the vehicle-treated rats at 28 days. Furthermore, the morphology of the nerve cells was better preserved in the TAT-NBD group, and these cells displayed less neurodegeneration and astrocytosis. Simultaneously, apoptosis in the brain was attenuated, and the levels of the TNF-α and IL-1ß proteins were decreased (p < 0.01). These results suggested that NF-κB was activated, and inhibition of NF-κB activation by TAT-NBD not only attenuated the acute neurotoxicity, apoptosis, and inflammation, but also improved the long term neurobehavioral impairments in the kernicterus model rats in vivo. Thus, inhibiting NF-κB activation might be a potential therapeutic approach for kernicterus.

Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo.

Central venous catheters are widely used in neonatal intensive care units (NICUs) nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs) is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of bromhexine, exhibits antimicrobial activity against strains producing biofilm and enhances the bactericidal effect of some antibiotic by breaking the structure of biofilm. In this study, we aimed to determine the effect of ambroxol with vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation with a tube covered with S. epidermidis biofilm. The rabbits received one of the following four treatments by means of antibiotic lock therapy: normal heparin, ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The microstructure of the biofilm was assessed by scanning electron microscopy (SEM). The number of bacterial colonies in the organs (liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. Pathological changes in the organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining. The ambroxol exhibits significant efficacy to potentiate the bactericidal effect of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S. epidermidis biofilms in vivo. These results provide the basis of a useful anti-infection strategy for the treatment of CRBSIs.

Does Streptococcus mitis, a neonatal oropharyngeal bacterium, influence the pathogenicity of Pseudomonas aeruginosa?

Microorganisms in a biofilm might promote or suppress each other. We previously found that Pseudomonas aeruginosa (P. aeruginosa) and the normal colonized bacteria in the oropharynx, Streptococcus mitis (S. mitis), were the most common bacteria in the biofilm found on newborns' endotracheal tubes. Here, we found that S. mitis enhanced the adhesion and biofilm formation of P. aeruginosa. Furthermore, it alleviated the immune response induced by P. aeruginosa. These findings remind us that we should not ignore the role of traditionally viewed non-pathogenic bacteria in biofilms and provide new insights into exploring bacterial interaction mechanisms in biofilm related infections.