Composite hydrogels with antioxidant and robust adhesive properties for the prevention of radiation-induced dermatitis.

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.

Time-lag and accumulation responses of vegetation growth to average and extreme precipitation and temperature events in China between 2001 and 2020.

Climate change is often closely related to vegetation dynamics; time lag (Tlag) and accumulative effects (Tacc) are non-negligible phenomena when studying the interaction between climate and vegetation. But, amidst the escalating frequency of extreme climatic events, the quantification of temporal effects (Teffects) of such extremes on vegetation remains scarce. This research quantifies the Tlag and Tacc responses of China's vegetation to episodes of extreme temperature and precipitation since the early 2000s, utilizing daily meteorological data series. Overall, the precipitation in China has become wetter, and nighttime temperatures have risen significantly. The proportion of areas with Teffects ranged from 1.15 % to 15.95 %, and the correlation coefficient between the climate indices and the Normalized Difference Vegetation Index (NDVI) increased by 0.05 to 0.38 when considering the Teffects, compared to not considering it. The Tacc of vegetation had the strongest response (70.74-88.01 %) to extreme events among all the tested climate indices. Moreover, the Tacc of consecutive climate events had a greater impact on vegetation growth than individual climate event. The average Tacc for extreme temperature and extreme precipitation was 1.7-3.09 months and 2.17-3.25 months, respectively. Events like the over 95 % (R95p) and 99 % (R99p) percentile heavy precipitation and the maximum precipitation amount in one day (Rx1day) caused significant Teffects on NDVI. In addition, 90 % of grasslands exhibit Tacc, mainly contributed by the extreme precipitation indices (55.7 %), while the Teffects of forests were stronger than those of extreme temperature. Furthermore, NDVI was more affected by annual precipitation than by extreme precipitation, but the opposite was true for temperature. The results of this study highlight the importance of considering the Tlag and Tacc when predicting the effects of climate change on vegetation dynamics.

Survival analysis of teeth following clinical crown lengthening and crown insertion procedures up to 14 years: A retrospective cohort study.

BACKGROUND: The purpose of this study was to conduct survival analysis of teeth following clinical crown lengthening procedures (CLPs) and crown insertions via a retrospective cohort study. METHODS: Patient- and tooth-related data were collected from 268 participants who received CLPs from 2009 to 2015. The Kaplan-Meier curve and the log-rank tests were used to estimate the probability of survival and compare the survival probabilities among different variables. A Cox multivariate proportional hazard regression model was used to investigate the collective effects of root canal treatment (RCT) and the types of opposing dentition. RESULTS: The rate of tooth loss was 21.6% during the observation period from 1 to 14 years, with 58 teeth extracted. The most attributable reason for tooth extraction was coronal tooth fracture, followed by endodontic failure such as root fracture. The survival probability was 0.87 at 5 years and 0.7 at 10 years. No significant differences in the survival probabilities were found among different providers and locations, the presence of a post, and the types of crowns. The hazard ratio for tooth loss was 6.3, 95% confidence interval (CI) [2.6 to 20.9] in the teeth with RCT (p < 0.001) and 2.4, 95% CI [1.1 to 4.8] in the teeth occluding implant-retained prostheses (p = 0.016). CONCLUSIONS: Tooth loss following CLPs and crown insertions appeared least among the teeth without RCT when occluding natural teeth, while tooth loss was most among the teeth with RCT when occluding implants.

Predictive model for assessing malnutrition in elderly hospitalized cancer patients: A machine learning approach.

BACKGROUND: Malnutrition is prevalent among elderly cancer patients. This study aims to develop a predictive model for malnutrition in hospitalized elderly cancer patients. METHODS: Data from January 2022 to January 2023 on cancer patients aged 60+ were collected, involving 22 variables. Key variables were identified using the LASSO (Least Absolute Shrinkage and Selection Operator) method, and nine machine learning models were tested. SHAP was used to interpret the XGBoost model. Malnutrition prevalence was assessed. RESULTS: Among 450 participants, 46.4 % were malnourished. Key predictors identified were ADL (Activities of Daily Living), ALB (Albumin), BMI (Body Mass Index) and age. XGBoost had the highest AUC of 0.945, accuracy of 0.872, and sensitivity of 0.968. Higher ADL and age increased malnutrition risk, while lower ALB and BMI reduced it. CONCLUSIONS: The XGBoost model is highly effective in detecting malnutrition in elderly cancer patients, enabling early and rapid nutritional assessments.

Recent advance in preparation of lignin nanoparticles and their medical applications: A review.

BACKGROUND: Lignin has attracted a lot of attention because it is non-toxic, renewable and biodegradable. Lignin nanoparticles (LNPs) have high specific surface area and specific surface charges. It provides LNPs with good antibacterial and antioxidant properties. LNPs preparation has become clear, however, the application remains in the early stages. PURPOSE: A review centric research has been conducted, reviewing existing literature to accomplish a basic understanding of the medical applications of LNPs. METHODS: Initially, we extensively counseled the heterogeneity of lignin from various sources. The size and morphology of LNPs from different preparation process were then discussed. Subsequently, we focused on the potential medical applications of LNPs, including drug delivery, wound healing, tissue engineering, and antibacterial agents. Lastly, we explained the significance of LNPs in terms of antibacterial, antioxidant and biocompatibility, especially highlighting the need for an integrated framework to understand a diverse range of medical applications of LNPs. RESULTS: We outlined the chemical structure of different type of lignin, and highlighted the advanced methods for lignin nanoparticles preparation. Moreover, we provided an in-depth review of the potential applications of lignin nanoparticles in various medical fields, especially in drug carriers, wound dressings, tissue engineering components, and antimicrobial agents. CONCLUSION: This review provides a detailed overview on the current state and progression of lignin nanoparticles for medical applications.

A Novel Strategy for Fabrication of Polyamide 66/Nanohydroxyapatite Composite Bone Repair Scaffolds by Low-Temperature Three-Dimensional Printing.

Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.

Neurobiological mechanisms of botulinum neurotoxin-induced analgesia for neuropathic pain.

Botulinum neurotoxins (BoNTs) are a family of neurotoxins produced by Clostridia and other bacteria that induce botulism. BoNTs are internalized into nerve terminals at the site of injection and cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins to inhibit the vesicular release of neurotransmitters. BoNTs have been approved for multiple therapeutic applications, including the treatment of migraines. They have also shown efficacies for treating neuropathic pain, such as diabetic neuropathy, and postherpetic and trigeminal neuralgia. However, the mechanisms underlying BoNT-induced analgesia are not well understood. Peripherally administered BoNT is taken up by the nerve terminals and reduces the release of glutamate, calcitonin gene-related peptide, and substance P, which decreases neurogenic inflammation in the periphery. BoNT is retrogradely transported to sensory ganglia and central terminals in a microtubule-dependent manner. BoNTs decrease the expression of pronociceptive genes (ion channels or cytokines) from sensory ganglia and the release of neurotransmitters and neuropeptides from primary afferent central terminals, which likely leads to decreased central sensitization in the dorsal horn of the spinal cord or trigeminal nucleus. BoNT-induced analgesia is abolished after capsaicin-induced denervation of transient receptor potential vanilloid 1 (TRPV1)-expressing afferents or the knockout of substance P or the neurokinin-1 receptor. Although peripheral administration of BoNT leads to changes in the central nervous system (e.g., decreased phosphorylation of glutamate receptors in second-order neurons, reduced activation of microglia, contralateral localization, and cortical reorganization), whether such changes are secondary to changes in primary afferents or directly mediated by trans-synaptic, transcytotic, or the hematogenous transport of BoNT is controversial. To enhance their therapeutic potential, BoNTs engineered for specific targeting of nociceptive pathways have been developed to treat chronic pain. Further mechanistic studies on BoNT-induced analgesia can enhance the application of native or engineered BoNTs for neuropathic pain treatment with improved safety and efficacy.

Dapagliflozin attenuates LPS-induced myocardial injury by reducing ferroptosis.

Septic cardiomyopathy is a severe cardiovascular disease with a poor prognosis. Previous studies have reported the involvement of ferroptosis in the pathogenesis of septic cardiomyopathy. SGLT2 inhibitors such as dapagliflozin have been demonstrated to improve ischemia-reperfusion injury by alleviating ferroptosis in cardiomyocyte. However, the role of dapagliflozin in sepsis remains unclear. Therefore, our study aims to investigate the therapeutic effects of dapagliflozin on LPS-induced septic cardiomyopathy. Our results indicate that dapagliflozin improved cardiac function in septic cardiomyopathy experimental mice. Mechanistically, dapagliflozin works by inhibiting the translation of key proteins involved in ferroptosis, such as GPX4, FTH1, and SLC7A11. It also reduces the transcription of lipid peroxidation-related mRNAs, including PTGS2 and ACSL4, as well as iron metabolism genes TFRC and HMOX1.

Physical and oxidative stability of flaxseed oil-in-water emulsions prepared by natural lignin-carbohydrate complex.

Flaxseed oil, rich in α-linolenic acid, plays a crucial role in various physiological processes. However, its stability presents certain challenges. In this study, the natural lignin-carbohydrate complex (LCC) was used to prepare the physical and oxidative stability of flaxseed oil-in-water emulsions. The LCC was characterized by HPLC, GPC, and FT-IR. The stability of emulsions was evaluated by viscosity, modulus, and micro-morphology changes. Then, the oxidation products were monitored by UV-vis spectrophotometer and HPLC. The results revealed that the high internal phase emulsion (HIPE) was successfully prepared with 2.5 wt% LCC at an oil/water ratio of 75/25 (v/v). Small droplet size (13.361 µm) and high viscosity (36,500 mPa·s) were found even after 30-day storage. Steric interactions of the LCC play a crucial role in ensuring stability, intricately linked to the interfacial properties of the emulsion. Meanwhile, the oxidative stability of α-linolenic acid in the encapsulated flaxseed oil was significantly higher than that in the bulk flaxseed oil. The results revealed that the LCC as a suitable emulsifier opens a new window for the storage of functional lipids rich in polyunsaturated fatty acids.

A spectral framework to map QTLs affecting joint differential networks of gene co-expression.

Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype → expression → phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype → network → phenotype mechanism. Here, we develop a network-based method, called snQTL, to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.

Later-melting rather than thickening of snowpack enhance the productivity and alter the community composition of temperate grassland.

Snowpack is closely related to vegetation green-up in water-limited ecosystems, and has effects on growing-season ecosystem processes. However, we know little about how changes in snowpack depth and melting timing affect primary productivity and plant community structure during the growing season. Here, we conducted a four-year snow manipulation experiment exploring how snow addition, snowmelt delay and their combination affect aboveground net primary productivity (ANPP), species diversity, community composition and plant reproductive phenology in seasonally snow-covered temperate grassland in northern China. Snow addition alone increased soil moisture and nutrient availability during early spring, while did not change plant community structure and ANPP. Instead, snowmelt delay alone postponed plant reproductive phenology, and increased ANPP, decreased species diversity and altered species composition. Grasses are more sensitive to changes in snowmelt timing than forbs, and early-flowering forbs showed a higher sensitivity compared to late-flowering forbs. The effect of snowmelt delay on ANPP and species diversity was offset by snow addition, probably because the added snow unnecessarily lengthens the snow-covering duration. The disparate effects of changes in snowpack depth and snowmelt timing necessitate their discrimination for more mechanistic understanding on the effects of snowpack changes on ecosystems. Our study suggests that it is essential to incorporate non-growing-season climate change events (in particular, snowfall and snowpack changes) to comprehensively disclose the effects of climate change on community structure and ecosystem functions.

A contactless monitoring system for accurately predicting energy expenditure during treadmill walking based on an ensemble neural network.

The monitoring of treadmill walking energy expenditure (EE) plays an important role in health evaluations and management, particularly in older individuals and those with chronic diseases. However, universal and highly accurate prediction methods for walking EE are still lacking. In this paper, we propose an ensemble neural network (ENN) model that predicts the treadmill walking EE of younger and older adults and stroke survivors with high precision based on easy-to-obtain features. Compared with previous studies, the proposed model reduced the estimation error by 13.95% and 66.20% for stroke survivors and younger adults, respectively. Furthermore, a contactless monitoring system was developed based on Kinect, mm-wave radar, and ENN algorithms, and the treadmill walking EE was monitored in real time. This ENN model and monitoring system can be combined with smart devices and treadmill, making them suitable for evaluating, monitoring, and tracking changes in health during exercise and in rehabilitation environments.

Forced mouth opening induces post-traumatic hyperalgesia and associated peripheral sensitization after temporomandibular joints injury in mice.

Temporomandibular disorder (TMD) is the most prevalent painful condition in the craniofacial area. The pathophysiology of TMD is not fully understood, and it is necessary to understand pathophysiology underlying painful TMD conditions to develop more effective treatment methods. Recent studies suggested that external or intrinsic trauma to TMJ is associated with chronic TMD in patients. Here, we investigated the effects of the TMJ trauma through forced-mouth opening (FMO) in mice to determine pain behaviors and peripheral sensitization of trigeminal nociceptors. FMO increased mechanical hyperalgesia assessed by von Frey test, spontaneous pain-like behaviors assessed by mouse grimace scale, and anxiety-like behaviors assessed by open-field test. In vivo GCaMP Ca 2+ imaging of intact trigeminal ganglia (TG) showed increased spontaneous Ca 2+ activity and mechanical hypersensitivity of TG neurons in the FMO compared to the sham group. Ca 2+ responses evoked by cold, heat, and capsaicin stimuli were also increased. FMO-induced hyperalgesia and neuronal hyperactivities were not sex dependent. TG neurons sensitized following FMO were primarily small to medium-sized nociceptive afferents. Consistently, most TMJ afferents in the TG were small-sized peptidergic neurons expressing calcitonin gene-related peptides, whereas nonpeptidergic TMJ afferents were relatively low. FMO-induced intraneural inflammation in the surrounding tissues of the TMJ indicates potentially novel mechanisms of peripheral sensitization following TMJ injury. These results suggest that the TMJ injury leads to persistent post-traumatic hyperalgesia associated with peripheral sensitization of trigeminal nociceptors.

MMCT-Loop: a mix model-based pipeline for calling targeted 3D chromatin loops.

Protein-specific Chromatin Conformation Capture (3C)-based technologies have become essential for identifying distal genomic interactions with critical roles in gene regulation. The standard techniques include Chromatin Interaction Analysis by Paired-End Tag (ChIA-PET), in situ Hi-C followed by chromatin immunoprecipitation (HiChIP) also known as PLAC-seq. To identify chromatin interactions from these data, a variety of computational methods have emerged. Although these state-of-art methods address many issues with loop calling, only few methods can fit different data types simultaneously, and the accuracy as well as the efficiency these approaches remains limited. Here we have generated a pipeline, MMCT-Loop, which ensures the accurate identification of strong loops as well as dynamic or weak loops through a mixed model. MMCT-Loop outperforms existing methods in accuracy, and the detected loops show higher activation functionality. To highlight the utility of MMCT-Loop, we applied it to conformational data derived from neural stem cell (NSCs) and uncovered several previously unidentified regulatory regions for key master regulators of stem cell identity. MMCT-Loop is an accurate and efficient loop caller for targeted conformation capture data, which supports raw data or pre-processed valid pairs as input, the output interactions are formatted and easily uploaded to a genome browser for visualization.

Nuclear localization of Argonaute 2 is affected by cell density and may relieve repression by microRNAs.

Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. Localization of AGO is central to understanding miRNA action, yet the consequences of AGO being in the nucleus are undefined. We show nuclear enrichment of AGO2 in HCT116 cells grown in two-dimensional culture to high density, HCT116 cells grown in three-dimensional tumor spheroid culture, and human colon tumors. The shift in localization of AGO2 from cytoplasm to nucleus de-represses cytoplasmic AGO2-eCLIP targets that were candidates for canonical regulation by miRISC. Constitutive nuclear localization of AGO2 using an engineered nuclear localization signal increases cell migration. Critical RNAi factors also affect the localization of AGO2. Knocking out an enzyme essential for miRNA biogenesis, DROSHA, depletes mature miRNAs and restricts AGO2 localization to the cytoplasm, while knocking out the miRISC scaffolding protein, TNRC6, results in nuclear localization of AGO2. These data suggest that AGO2 localization and miRNA activity can be regulated depending on environmental conditions, expression of mature miRNAs, and expression of miRISC cofactors. Localization and expression of core miRISC protein machinery should be considered when investigating the roles of miRNAs.

Colchicine ameliorates short-term abdominal aortic aneurysms by inhibiting the expression of NLRP3 inflammasome components in mice.

BACKGROUND: Abdominal aortic aneurysms (AAA) are often associated with chronic inflammation and pose a significant risk to affected individuals. Colchicine, known for its anti-inflammatory properties, has shown promise in managing cardiovascular diseases. However, its specific role in the development of AAA remains poorly understood. METHODS AND RESULTS: In this study, we employed a short-term AAA model induced by angiotensin II (Ang II, 1000 ng/kg/min) and calcium chloride (CaCl2, 0.5 mol/l) in male ApoE-/- and C57BL/6 mice (8-12 weeks old) to investigate the effects of colchicine on AAA progression. Colchicine (0.4 mg/kg) was administered orally once daily, starting on the same day as AAA induction. After a 4-week duration, we observed a significant reduction in AAA diameter, degradation of elastic fibers, and expression of components related to the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome in the vessel wall of colchicine-treated mice compared to the saline group. Mechanistically, colchicine (5 µm/l, for 24h) inhibited the expression of NLRP3 inflammasome components through the P38-ERK/MicroRNA145-toll-like receptor 4 (TLR4) pathway in RAW264.7 cells. CONCLUSIONS: Our study demonstrates the effectiveness of colchicine in suppressing NLRP3 inflammasome components, thereby delaying AAA progression in the Ang II and CaCl2-induced short-term model. These findings suggest the potential of colchicine as a pharmacological treatment option for AAA.

Clinical application of lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture in the restoration of single anterior tooth loss / 口腔疾病防治

Objective@#To investigate the clinical effect of lithium disilicate glass ceramic cantilever resin-bonded fixed partial dentures (CRBFPDs) on single anterior tooth loss to provide a reference for the selection of restoration methods for single anterior tooth loss.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Forty-two patients with less than two anterior teeth with monomaxillary loss were included in this study. After 6 months, 1 year, 2 years, and 3 years, the aesthetic and functional effects of the restorations and the periodontal health status were evaluated, and the visual analog scale (VAS) was used to assess patient satisfaction.@*Results@#During the observation period, the connector fractured in one case within 3 months. One case had debonded within 2 years. The aesthetic restoration effect of all lithium disilicate glass ceramic CRBFPDs was categorized as Class A. The periodontal health was good, there was no clinical absorption in the soft and hard tissues of the abutment or subbridge, periodontal status according to the evaluation indices was classified as class A, and the total satisfaction rate of the patient was 100%.@*Conclusion@#For single anterior tooth loss patients, lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture can achieve the restoration effect of less invasion, better adhesion, aesthetics, comfort and good biocompatibility. With high patient satisfaction, it can be considered an ideal restoration method for replacing a single anterior tooth.

CRISPR/Cas9 systems: Delivery technologies and biomedical applications.

The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has brought about a significant revolution in the realm of managing human diseases, establishing animal models, and so on. To fully harness the potential of this potent gene-editing tool, ensuring efficient and secure delivery to the target site is paramount. Consequently, developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research. In this review, we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system. We also provide an in-depth analysis of physical, viral vector, and non-viral vector delivery strategies, including plasmid-, mRNA- and protein-based approach. In addition, we illustrate the biomedical applications of the CRISPR/Cas9 system. This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system, while also delineating future directions and prospects that could inspire innovative delivery strategies. This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

Association between cardiopulmonary bypass time and mortality among patients with acute respiratory distress syndrome after cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) can lead to lung injury and even acute respiratory distress syndrome (ARDS) through triggering systemic inflammatory response. The objective of this study was to investigate the impact of CPB time on clinical outcomes in patients with ARDS after cardiac surgery. METHODS: Totally, patients with ARDS after cardiac surgery in Beijing Anzhen Hospital from January 2005 to December 2015 were retrospectively included and were further divided into three groups according to the median time of CPB. The primary endpoints were the ICU mortality and in-hospital mortality, and ICU and hospital stay. Restricted cubic spline (RCS), logistic regression, cox regression model, and receiver operating characteristic (ROC) curve were adopted to explore the relationship between CPB time and clinical endpoints. RESULTS: A total of 54,217 patients underwent cardiac surgery during the above period, of whom 210 patients developed ARDS after surgery and were finally included. The ICU mortality and in-hospital mortality were 21.0% and 41.9% in all ARDS patients after cardiac surgery respectively. Patients with long CPB time (CPB time ≥ 173 min) had longer length of ICU stay (P = 0.011), higher ICU (P < 0.001) mortality and in-hospital(P = 0.002) mortality compared with non-CPB patients (CPB = 0). For each ten minutes increment in CPB time, the hazards of a worse outcome increased by 13.3% for ICU mortality and 9.3% for in-hospital mortality after adjusting for potential factors. ROC curves showed CPB time presented more satisfactory power to predict mortality compared with APCHEII score. The optimal cut-off value of CPB time were 160.5 min for ICU mortality and in-hospital mortality. CONCLUSIONS: Our findings demonstrated the significant prognostic value of CPB time in patients with ARDS after cardiac surgery. Longer time of CPB was associated with poorer clinical outcomes, and could be served as an indicator to predict short-term mortality in patients with ARDS after cardiac surgery.

Modulation of Gene Expression in the Eye with Antisense Oligonucleotides.

One advantage of antisense oligonucleotides (ASOs) for drug development is their long-lasting gene knockdown after administration in vivo. In this study, we examine the effect on gene expression after intraocular injection in target tissues in the eye. We examined expression levels of the Malat1 gene after intracameral or intravitreal (IV) injection of an anti-Malat1 ASO in corneal epithelium/stroma, corneal endothelium, lens capsule epithelium, neurosensory retina, and retinal pigment epithelium/choroid of the mouse eye. We assessed potency of the compound at 7 days as well as duration of the gene knockdown at 14, 28, 60, 90, and 120 days. The ASO was more potent when delivered by IV injection relative to intracameral injection, regardless of whether the tissues analyzed were at the front or back of the eye. For corneal endothelium, inhibition was >50% after 120 days for ASO at 50 µg. At IV dosages of 6 µg, we observed >75% inhibition of gene expression in the retina and lens epithelium for up to 120 days. ASOs have potential as long-lasting gene knockdown agents in the mouse eye, but efficacy varies depending on the specific ocular target tissue and injection protocol.