Construction of a layer-by-layer self-assembled rosemarinic acid delivery system on the surface of CFRPEEK implants for enhanced anti-inflammatory and osseointegration activities.

Carbon fiber-reinforced polyether ether ketone (CFRPEEK) implants have attracted widespread attention in the field of clinical bone defect repair. However, the surface bioinertness confines the application of CFRPEEK implants. Inspired by the study of rosmarinic acid (RA)-promoted osteogenic differentiation, a self-assembly surface modification method based on electrostatic interactions, involving deposition of sodium carboxymethyl cellulose/chitosan and rosmarinic acid layer by layer on the surface of poly-L-lysine modified hydroxy CFRPEEK (SCPP/CC5@RA), is proposed to introduce RA on the surface of CFRPEEK for bioactivation. After layer-by-layer self-assembly (LBL), the surface of SCPP/CC5@RA exhibits weak electrophoresis (11.43 eV), suitable hydrophilicity, and bioactivity. The results of in vitro studies indicate that the RA release behavior of SCPP/CC5@RA effectively regulates the immune-inflammatory response and promotes the differentiation of osteoblasts. The rapid release of RA (0.17 µg mL-1) in the initial stage can downregulate the secretion of inflammation-related cytokines and significantly reduce oxidative stress levels; the sustained release of RA (0.06 µg mL-1) in the late stage can upregulate the expression of osteogenesis-related genes and induce mineralization of osteoblasts. Moreover, the rabbit tibia defect model demonstrates that the LBL technique can enhance the osseointegration of CFRPEEK implants. Compared with the control group, the bone trabecular thickness of the SCPP/CC5@RA group increases by 1.36 times, and the maximum pushing force increases by 2.67 times. In summary, this study provides a promising LBL based RA delivery system for the development of a dual-functional CFRPEEK implant in the field of bone implant biomaterials.

Piceatannol protects against myocardial ischemia/reperfusion injury by inhibiting ferroptosis via Nrf-2 signaling-mediated iron metabolism.

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PURPOSE: This study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. METHODS: An ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. RESULTS: During ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. CONCLUSIONS: PCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.

Survival benefit of surgery for second primary esophageal cancer following gastrointestinal cancer: a population-based study.

BACKGROUND: The incidence of second primary malignancy is increasing. However, although there is some information on second primary esophageal cancer (SPEC) itself, there is no study or guideline on the use of surgery for SPEC after gastrointestinal cancer (SPEC-GC). Thus, this study aimed to gather evidence for the benefits of surgery by analyzing a national cohort and determining the prognostic factors and clinical treatment decisions for SPEC-GC. METHODS: Data for patients with SPEC-GC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The prognostic factors of SPEC-GC were investigated by stepwise Cox proportional hazards regression and Kaplan-Meier analyses for overall survival and cancer-specific survival. RESULTS: A total of 8308 patients with SPEC were selected, including 582 patients with SPEC-GC. Multivariate analysis revealed that surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were significant predictors of survival outcomes (P < .05). Surgery seemed to improve the prognosis of patients with SPEC-GC significantly compared with no surgery and chemoradiotherapy (P < .001). CONCLUSIONS: Surgery should be considered as the main treatment for SPEC-GC. Surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were found to be independent prognostic factors for these patients. These factors should be considered in the clinical diagnosis and treatment of SPEC-GC.

Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. METHODS: CD animal models were created using Il-10-/- mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10-/- mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10-/- mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10-/- mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10-/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.

Effect of Glass Fiber-Reinforced Plastic Waste on the Mechanical Properties of Concrete and Evaluation of Its Feasibility for Reuse in Concrete Applications.

The disposal of glass fiber-reinforced plastic (GFRP) waste has become an urgent issue in both the engineering and environmental fields. In this study, the feasibility of reusing mechanically recycled GFRP in concrete was evaluated. Secondary screening of the recycled material was conducted to obtain different types of products, and the recycled GFRP (rGFRP) was characterized. Subsequently, the effect of rGFRP on concrete performance was evaluated using different dosages (0%, 1%, 3%, 5%) of rGFRP powder and rGFRP cluster (with different sizes and fiber contents) to replace fine aggregate in concrete preparation. The experimental results indicated that the addition of rGFRP powder has no significant impact on the mechanical properties of concrete, while the addition of a small amount of rGFRP cluster slightly improves the compressive strength and splitting tensile strength of concrete. Additionally, the short fibers in rGFRP improve the failure mode of concrete, and increased fiber content and longer fiber length demonstrate a more pronounced reinforcing effect. The challenges and potential directions for future research in the realm of reusing rGFRP in concrete are discussed at the end. A systematic process for reusing GFRP waste in concrete is proposed to address the primary challenges and provide guidance for its practical engineering application.

Diurnal migration patterns in willow warblers differ between the western and eastern flyways.

It is a long-standing view that the main mechanism maintaining narrow migratory divides in passerines is the selection against intermediate and suboptimal migratory direction, but empirical proof of this is still lacking. We present novel results from a willow warbler migratory divide in central Sweden from where birds take the typical SW and SE as well as intermediate routes to winter quarters in Africa. We hypothesized that individuals that take the intermediate route are forced to migrate in daytime more often when crossing wide ecological barriers than birds that follow the typical western or eastern flyways. Analyses of geolocator tracks of willow warblers breeding across the entire Sweden, including the migratory divide, provided no support for our hypothesis. Instead, birds that migrated along the western flyway were the most likely to undertake full day flights. The probability of migrating for a full day when crossing major barriers declined linearly from west to east. We speculate that this difference is possibly caused by more challenging conditions in the western part of the Sahara Desert, such as the lack of suitable day-time roost sites. However, it may equally likely be that willow warblers benefit from migrating in daytime if favorable tailwinds offer assistance.

Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling.

BACKGROUND AND AIMS: M1 polarization of macrophages in the intestine is an important maintenance factor of the inflammatory response in Crohn's disease (CD). Eriocalyxin B (EriB) is a natural medicine that antagonizes inflammation. Our study aimed to determine the effects of EriB on CD-like colitis in mice, as well as the possible mechanism. METHODS: 2,4,6-trinitrobenzene sulfonic acid (TNBS) mice and Il-10-/- mice were used as CD animal models, and the therapeutic effect of EriB on CD-like colitis in mice was addressed by the disease activity index (DAI) score, weight change, histological analysis and flow cytometry assay. To assess the direct role of EriB in regulating macrophage polarization, bone marrow-derived macrophages (BMDMs) were induced to M1 or M2 polarization separately. Molecular docking simulations and blocking experiments were performed to explore the potential mechanisms by which EriB regulates the macrophage polarization. RESULTS: EriB treatment reduced body weight loss, DAI score and histological score, demonstrating the improvement of colitis symptoms in mice. In vivo and in vitro experiments both showed that EriB decreased the M1 polarization of macrophages, and suppressed the release of proinflammatory cytokines (IL-1ß, TNF-α and IL-6) in mouse colons and BMDMs. The activation of Janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1) signals could be inhibited by EriB, which may be related to the regulation of EriB on M1 polarization. CONCLUSIONS: EriB inhibits the M1 polarization of macrophages by attenuating the JAK2/STAT1 pathway, which partially explains the potential mechanism by which EriB ameliorates colitis in mice, and provides a new regimen for the clinical treatment of CD.

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study.

Purpose: To explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis. Patients and methods: Three independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC). Results: In the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue. Conclusion: A novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Piceatannol protects against age-related hearing loss by inhibiting cellular pyroptosis and inflammation through regulated Caspase11-GSDMD pathway.

Age-related hearing loss (ARHL) is a common issue associated with aging. One of the typical causes of hearing loss is the damage to inner ear hair cells. In addition, oxidative stress and inflammation contribute to ARHL. To avoid excessive inflammatory responses, non-classical scorch death pathway by cell membrane lipopolysaccharide (LPS) activates of caspase-11. Piceatannol (PCT) is also known for anti-tumor, antioxidant and anti-inflammatory effects; however, the protective effect of piceatannol (PCT) on ARHL is unclear. The aim of this study was to elucidate the mechanism underlying protective effect of PCT on ARHL-induced inner ear hair cell damage. In vivo experiments showed that PCT could protect mice from inflammatory aging-induced hearing loss as well as from inner hair cells (IHC) and spiral ganglion (SG) deficits. In addition, inflammatory vesicle inhibitor BAY11-7082 ameliorated ARHL, inhibited NLRP3 and reduced GSDMD expression. In in vitro experiments we used LPS and D-gal to simulate the aging inflammatory environment. The results showed that intracellular reactive oxygen species levels, expression of Caspase-11, NLRP3, and GSDMD were significantly increased, yet treatment with PCT or BAY11-7082 significantly improved HEI-OC-1 cell injury while reducing inflammation-associated protein expression as well as the occurrence of pyroptosis. In conclusion, these results suggest a protective role for PCT against ARHL, possibly through Caspase-11-GSDMD pathway. Our findings may provide a new target and theoretical basis for hearing loss treatment using PCT.

Anomalous magnetoresistance by breaking ice rule in Bi2Ir2O7/Dy2Ti2O7 heterostructure.

While geometrically frustrated quantum magnets host rich exotic spin states with potentials for revolutionary quantum technologies, most of them are necessarily good insulators which are difficult to be integrated with modern electrical circuit. The grand challenge is to electrically detect the emergent fluctuations and excitations by introducing charge carriers that interact with the localized spins without destroying their collective spin states. Here, we show that, by designing a Bi2Ir2O7/Dy2Ti2O7 heterostructure, the breaking of the spin-ice rule in insulating Dy2Ti2O7 leads to a charge response in the conducting Bi2Ir2O7 measured as anomalous magnetoresistance during the field-induced Kagome ice-to-saturated ice transition. The magnetoresistive anomaly also captures the characteristic angular and temperature dependence of this ice-rule-breaking transition, which has been understood as magnetic monopole condensation. These results demonstrate a novel heteroepitaxial approach for electronically probing the transition between exotic insulating spin states, laying out a blueprint for the metallization of frustrated quantum magnets.

Migration direction in a songbird explained by two loci.

Migratory routes and remote wintering quarters in birds are often species and even population specific. It has been known for decades that songbirds mainly migrate solitarily, and that the migration direction is genetically controlled. Yet, the underlying genetic mechanisms remain unknown. To investigate the genetic basis of migration direction, we track genotyped willow warblers Phylloscopus trochilus from a migratory divide in Sweden, where South-West migrating, and South-East migrating subspecies form a hybrid swarm. We find evidence that migration direction follows a dominant inheritance pattern with epistatic interaction between two loci explaining 74% of variation. Consequently, most hybrids migrate similarly to one of the parental subspecies, and therefore do not suffer from the cost of following an inferior, intermediate route. This has significant implications for understanding the selection processes that maintain narrow migratory divides.

Ni Single Atoms on MoS2 Nanosheets Enabling Enhanced Kinetics of Li-S Batteries.

The practical application of Li-S batteries is seriously hindered due to its shuttle effect and sluggish redox reaction, which requires a better functional separator to solve the problems. Herein, polypropylene separators modified by MoS2 nanosheets with atomically dispersed nickel (Ni-MoS2 ) are prepared to prevent the shuttle effect and facilitate the redox kinetics for Li-S batteries. Compared with pristine MoS2 nanosheets, Ni-MoS2 nanosheets exhibit both excellent adsorption and catalysis performance for overcoming the shuttle effect. Assembled with this novel separator, the Li-S batteries exhibit an admirable cycling stability at 2 C over 400 cycles with 0.01% per cycle decaying. In addition, even with a high sulfur loading of 7.5 mg cm-2 , the battery still provides an initial capacity of 6.9 mAh cm-2 and remains 5.9 mAh cm-2 after 50 cycles because of the fast convention of polysulfides catalyzed by Ni-MoS2 nanosheets, which is further confirmed by the density functional theory (DFT) calculations. Therefore, the proposed strategy is expected to offer a new thought for single atom catalyst applying in Li-S batteries.

Expectation-maximization algorithm leads to domain adaptation for a perineural invasion and nerve extraction task in whole slide digital pathology images.

In addition to lymphatic and vascular channels, tumor cells can also spread via nerves, i.e., perineural invasion (PNI). PNI serves as an independent prognostic indicator in many malignancies. As a result, identifying and determining the extent of PNI is an important yet extremely tedious task in surgical pathology. In this work, we present a computational approach to extract nerves and PNI from whole slide histopathology images. We make manual annotations on selected prostate cancer slides once but then apply the trained model for nerve segmentation to both prostate cancer slides and head and neck cancer slides. For the purpose of multi-domain learning/prediction and investigation on the generalization capability of deep neural network, an expectation-maximization (EM)-based domain adaptation approach is proposed to improve the segmentation performance, in particular for the head and neck cancer slides. Experiments are conducted to demonstrate the segmentation performances. The average Dice coefficient for prostate cancer slides is 0.82 and 0.79 for head and neck cancer slides. Comparisons are then made for segmentations with and without the proposed EM-based domain adaptation on prostate cancer and head and neck cancer whole slide histopathology images from The Cancer Genome Atlas (TCGA) database and significant improvements are observed.

An epitaxial graphene platform for zero-energy edge state nanoelectronics.

Graphene's original promise to succeed silicon faltered due to pervasive edge disorder in lithographically patterned deposited graphene and the lack of a new electronics paradigm. Here we demonstrate that the annealed edges in conventionally patterned graphene epitaxially grown on a silicon carbide substrate (epigraphene) are stabilized by the substrate and support a protected edge state. The edge state has a mean free path that is greater than 50 microns, 5000 times greater than the bulk states and involves a theoretically unexpected Majorana-like zero-energy non-degenerate quasiparticle that does not produce a Hall voltage. In seamless integrated structures, the edge state forms a zero-energy one-dimensional ballistic network with essentially dissipationless nodes at ribbon-ribbon junctions. Seamless device structures offer a variety of switching possibilities including quantum coherent devices at low temperatures. This makes epigraphene a technologically viable graphene nanoelectronics platform that has the potential to succeed silicon nanoelectronics.

Case report: Eosinophilic pneumonia associated with vedolizumab therapy in a patient with ulcerative colitis.

Extraintestinal manifestations are common in patients with inflammatory bowel disease, while respiratory involvement is less common. Vedolizumab is a new class of anti-integrin biological agents approved for treating inflammatory bowel disease. In this report, we present the case of a 38-year-old patient with ulcerative colitis for 7 years who developed cough, fever, and pulmonary infiltrates after taking vedolizumab. There was a spontaneous improvement in clinical symptoms and radiological abnormalities after discontinuing vedolizumab and introducing steroids. Despite the rarity of vedolizumab-induced eosinophilic pneumonia, the case reports indicate that patients with unexplained respiratory symptoms that are taking vedolizumab should be fully contemplated.

Recent Developments and Current Applications of Organic Nanomaterials in Cartilage Repair.

Regeneration of cartilage is difficult due to the unique microstructure, unique multizone organization, and avascular nature of cartilage tissue. The development of nanomaterials and nanofabrication technologies holds great promise for the repair and regeneration of injured or degenerated cartilage tissue. Nanomaterials have structural components smaller than 100 nm in at least one dimension and exhibit unique properties due to their nanoscale structure and high specific surface area. The unique properties of nanomaterials include, but are not limited to, increased chemical reactivity, mechanical strength, degradability, and biocompatibility. As an emerging nanomaterial, organic nanocomposites can mimic natural cartilage in terms of microstructure, physicochemical, mechanical, and biological properties. The integration of organic nanomaterials is expected to develop scaffolds that better mimic the extracellular matrix (ECM) environment of cartilage to enhance scaffold-cell interactions and improve the functionality of engineered tissue constructs. Next-generation hydrogel technology and bioprinting can be used not only for healing cartilage injury areas but also for extensive osteoarthritic degenerative changes within the joint. Although more challenges need to be solved before they can be translated into full-fledged commercial products, nano-organic composites remain very promising candidates for the future development of cartilage tissue engineering.

Recent Developments and Current Applications of Hydrogels in Osteoarthritis.

Osteoarthritis (OA) is a common degenerative joint disease that causes disability if left untreated. The treatment of OA currently requires a proper delivery system that avoids the loss of therapeutic ingredients. Hydrogels are widely used in tissue engineering as a platform for carrying drugs and stem cells, and the anatomical environment of the limited joint cavity is suitable for hydrogel therapy. This review begins with a brief introduction to OA and hydrogels and illustrates the effects, including the analgesic effects, of hydrogel viscosupplementation on OA. Then, considering recent studies of hydrogels and OA, three main aspects, including drug delivery systems, mesenchymal stem cell entrapment, and cartilage regeneration, are described. Hydrogel delivery improves drug retention in the joint cavity, making it possible to deliver some drugs that are not suitable for traditional injection; hydrogels with characteristics similar to those of the extracellular matrix facilitate cell loading, proliferation, and migration; hydrogels can promote bone regeneration, depending on their own biochemical properties or on loaded proregenerative factors. These applications are interlinked and are often researched together.

One-Pot Preparation of Lithium Compensation Layer, Lithiophilic Layer, and Artificial Solid Electrolyte Interphase for Lean-Lithium Metal Anode.

Lithium metal is an ideal anode for high-energy-density batteries. However, the low Coulomb efficiency and the generation of dendrites pose a significant limitation to its practical application, while the excess lithium in the battery also generates serious safety concerns. Herein, a layer-by-layer optimized multilayer structure integrating an artificial solid electrolyte interphase (LiF) layer, a lithiophilic (LixAu alloy) layer, and a lithium compensation layer is reported for a lean-lithium metal battery, where each layer acts synergistically to stabilize the lithium deposition behaviors and enhances the cycling performance of the battery. The optimized anode could effectively induce homogeneous reversible lithium deposition under the synergistic effect of multilayer films and keep the integrity of the morphological structure unbroken during the deposition. The presence of the lithium compensation layer allows the half-cell to have a high initial CE of 158.9%, and the action of the LiF layer and lithiophilic layer maintains an average CE of 98.8% over 160 cycles, which further demonstrates the stability of the structure. As a result, when combined with LiFePO4 cathode, an initial capacity of 148 mAh g-1 and a retention rate of 97.5% over 130 cycles were achieved.

Efficacy of adaptive ventilation support combined with lung recruitment maneuvering for acute respiratory distress syndrome.

OBJECTIVE: This study was designed to evaluate the efficacy of adaptive support ventilation (ASV) and lung recruitment maneuvering (LRM) on the hemodynamics and respiratory mechanics of patients with acute respiratory distress syndrome (ARDS). METHODS: A total of 100 patients with ARDS admitted to the intensive care unit (ICU) of our hospital from July 2016 to October 2019 were randomly divided into the control group (n=50) receiving synchronized intermittent mandatory ventilation (SIMV) and the study group (n=50) receiving ASV + LRM. The hemodynamics, respiratory mechanics, oxygen metabolism parameters, pulmonary index of microcirculatory resistance and prognosis were compared between the two groups. RESULTS: No significant difference was observed between the two groups in terms of baseline data (P > 0.05). Positive end-expiratory pressure (PEEP), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), systemic vascular resistance index (SVRI), pulmonary arterial pressure (PAP), and cardiac output index (CI) were not significantly different between the two groups (P > 0.05). PEEP, peak inspiratory pressure (PIP), pulmonary vascular resistance index (PVRI), and extravascular lung water (EVLW) were lower, and arterial oxygen pressure (PaO2), global oxygen delivery (DO2), oxygen-uptake (VO2), and dynamic compliance (Cdyn) were higher in the study group than in the control group (P < 0.05). Time to withdrawal, APACHE II score, and length of stay in ICU were lower in the study group than in the control group (P < 0.05). CONCLUSION: ASV + LRM can improve respiratory mechanics, oxygen metabolism, reduce microcirculatory resistance, shorten ICU stay and alleviate the conditions of ARDS patients, but has no significant effect on hemodynamics.

Immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice / 数字中医药（英文）

@#Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice. Methods (i) Fifty male BALB/c mice were randomly divided into five groups (10 mice in each group): normal control (NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide (LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline (PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin (HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin (IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay (ELISA), and those of surfactant protein D (SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry (IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase (MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). (ii) Another 60 BALB/c mice were divided into six groups (10 mice in each group) : NC group, model control (MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinic-polycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent 45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection. Detection methods were identical to those described in (i) above. Results (i) CsA (30 mg/kg) increased the lung index of mice (P < 0.001), and decreased the spleen index (P < 0.01), thymus index (P < 0.05), and the serum level of IL-2 (P < 0.05). CsA (45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2 (P < 0.01) in mice, and increased the serum level of IL-1β (P < 0.05) and the protein level of lung SP-D (P <0.001). CsA (60 mg/kg) increased the lung index of mice (P < 0.01), the serum level of IL-1β (P < 0.05), the protein level of lung SP-D (P < 0.01), and the mRNA levels of lung MPO and SP-D ( P < 0.05), and decreased the thymus index of mice (P < 0.01). HE staining showed that 30, 45, and 60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice. (ii) After pachymaran intervention in MC mice, the spleen and thymus indexes (P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased (P < 0.05). Moreover, 50 mg/kg pachymaran increased the thymus index (P < 0.05) and decreased the lung index (P < 0.01) in MC group. Pachymaran (50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β (P < 0.001), and the mRNA levels of MPO and SP-D in lung tissues (P < 0.05) of mice. Pachymaran (100 mg/kg) increased the protein level of lung IL-2 (P < 0.01), decreased the protein level of lung SP-D (P < 0.01), and the mRNA level of IL-1β (P < 0.001) in the lung tissues of mice. Pachymaran (200 mg/kg) increased the serum level of IL-2 (P < 0.01) and lung IL-6 of mice (P < 0.05). Pachymaran (50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice (P < 0.05). Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.