Biodegradable zwitterionic polymer-cloaked defective metal-organic frameworks for ferroptosis-inducing cancer therapy.

Ferroptosis inhibits tumor growth by iron-dependently accumulating lipid peroxides (LPO) to a lethal extent, which can result from iron overload and glutathione peroxidase 4 (GPX4) inactivation. In this study, we developed biodegradable zwitterionic polymer-cloaked atorvastatin (ATV)-loaded ferric metal-organic frameworks (Fe-MOFs) for cancer treatment. Fe-MOFs served as nanoplatforms to co-deliver ferrous ions and ATV to cancer cells; the zwitterionic polymer membrane extended the circulation time of the nanoparticles and increased their accumulation at tumor sites. In cancer cells, the structure of the Fe-MOFs collapsed in the presence of glutathione (GSH), leading to the depletion of GSH and the release of ATV and Fe2+. The released ATV decreased mevalonate biosynthesis and GSH, resulting in GPX4 attenuation. A large number of reactive oxygen species were generated by the Fe2+-triggered Fenton reaction. This synergistic effect ultimately contributed to a lethal accumulation of LPO, causing cancer cell death. The findings both in vitro and in vivo suggested that this ferroptosis-inducing nanoplatform exhibited enhanced anticancer efficacy and preferable biocompatibility, which could provide a feasible strategy for anticancer therapy.

EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death.

TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape.

The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response warrant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cytoplasm. Put simply, lncRNA-BTX facilitates DHX9's return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.

Lysine methyltransferase SMYD2 inhibits antiviral innate immunity by promoting IRF3 dephosphorylation.

Phosphorylation of IRF3 is critical to induce type I interferon (IFN-I) production in antiviral innate response. Here we report that lysine methyltransferase SMYD2 inhibits the expressions of IFN-I and proinflammatory cytokines in macrophages upon viral infections. The Smyd2-deficient mice are more resistant to viral infection by producing more IFN-I and proinflammatory cytokines. Mechanistically, SMYD2 inhibits IRF3 phosphorylation in macrophages in response to viral infection independent of its methyltransferase activity. We found that SMYD2 interacts with the DNA-binding domain (DBD) and IRF association domain (IAD) domains of IRF3 by its insertion SET domain (SETi) and could recruit phosphatase PP1α to enhance its interaction with IRF3, which leads to decreased phosphorylation of IRF3 in the antiviral innate response. Our study identifies SMYD2 as a negative regulator of IFN-I production against virus infection. The new way of regulating IRF3 phosphorylation will provide insight into the understanding of IFN-I production in the innate response and possible intervention of the related immune disorders.

Highly efficient nanocomposite of Y2O3@biochar for oxytetracycline removal from solution: Adsorption characteristics and mechanisms.

Nano Y2O3-modified biochar composites (Y2O3@BC600) were fabricated successfully and exhibited great adsorption toward oxytetracycline (OTC). The Langmuir adsorption capacity of Y2O3@BC600-1:4 for OTC reached 223.46 mg/g, 10.52 times greater than that of BC600. The higher dispersion of Y2O3 nanoparticles, increased surface area of 175.65 m2/g and expanded porosity of 0.27 cm3/g accounted for higher OTC adsorption by Y2O3@BC600-1:4. Y2O3@BC600-1:4 could resist the interference of co-existing cations (Na+, K+, Mg2+, Ca2+) and anions (Cl-, NO3-, SO42-) on OTC removal. Y2O3 coating changed surface charge property of BC600, favoring the contribution of electrostatic interaction. Synchrotron radiation-based Fourier transform infrared spectroscopy detected obvious peak shift and intensity change of surface -OH when OTC adsorption occurred. Accordingly, stronger H-bonding (charge-assisted hydrogen bond, OTC-H2N+···HO-Y2O3@BC600-1:4) was proposed for OTC adsorption. Y2O3@BC600 exhibited renewability and stability in the adsorptive removal of OTC. Therefore, Y2O3@BC600 may be a novel and suitable adsorbent for antibiotic removal.

Fenton oxidation treatment of oxytetracycline fermentation residues: Harmless performance and bioresource properties.

The pharmaceutical factories of oxytetracycline (OTC) massively produce OTC fermentation residues (OFRs). The high content of residual OTC and antibiotic resistance genes in OFRs must to be considered and controlled at an acceptable level. This study therefore investigated the applicability of Fenton oxidation in OTC degradation and resistant gene inactivation of OFRs. The results revealed that Fe2+ as catalyzer could very rapidly activate H2O2 to produce HO•, leading to instantaneous degradation of OTC. The optimum conditions for OTC removal were 60 mM H2O2 and 140 mg/L Fe2+ under pH 7. After Fenton oxidation treatment, the release of water-soluble polysaccharides, NO3-N, and PO4-P was enhanced, whereas for proteins and NH3-N were reduced. Three soluble fluorescence components (humic, tryptophan-like, and humic acid-like substances) were identified through fluorescence spectra with parallel factor analysis, and their reduction exceeded 50% after Fenton oxidation. There were twelve intermediates and three degradation pathways of OTC in OFRs during Fenton process. According to toxicity prediction, the comprehensive toxicity of OTC in OFRs was alleviated via Fenton oxidation treatment. In addition, Fenton oxidation showed the ability to reduce antibiotic resistance genes and mobile genetic elements, and even tetO, tetG, intI1, and intI2 were eliminated completely. These results suggested that Fenton oxidation treatment could be an efficient strategy for removing OTC and resistance genes in OFRs.

Transcriptome analysis of human peri-implant soft tissue and periodontal gingiva: a paired design study.

OBJECTIVES: Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the soft tissue in vivo by using paired samples and compare the differences between peri-implant soft tissue and periodontal gingiva at the transcriptional level. METHODS: Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further verification was done by quantitative real-time PCR. RESULTS: Totally 3549 differentially expressed genes (DEGs) were found between peri-implant and periodontal groups. The Venn diagram further identified 185 DEGs in every pair of samples, of which the enrichment analysis identified significant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokine-cytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9, and SFRP2 were verified to be upregulated in peri-implant soft tissue. CONCLUSIONS: Peri-implant soft tissue showed altered expressions of several genes related to the cell-ECM interaction compared to periodontal gingiva. CLINICAL RELEVANCE: Compared to periodontal gingiva, altered cell-ECM interactions in peri-implant may contribute to the susceptibility of peri-implant diseases. At the transcriptional level, periodontal gingiva is generally considered the appropriate control for peri-implantitis, except regarding the cell-ECM interactions.

Type XV osteogenesis imperfecta: A novel mutation in the WNT1 gene, c.620G >A (p.R207H), is associated with an inner ear deformity.

The Wnt signaling pathway is vital in encouraging bone growth. WNT1 gene mutations have been identified as the major cause of type XV osteogenesis imperfecta (OI). Described here is a case of complex heterozygous WNT1 c.620G>A (p.R207H) and c.677C >T (p.S226L) OI caused by a novel mutation at locus c.620G >A (p.R207H). The female patient had type XV OI, distinguished by poor bone density, frequent fractures, a small stature, skull softening, lack of dentine hypoplasia, a brain malformation, and obvious blue sclera. A CT scan of the temporal bone revealed abnormalities of the inner ear, necessitating a hearing aid 8 months after birth. There was no family history of such disorders in the proband's parents. The proband inherited complex heterozygous WNT1 gene variants c.677C>T (p.S226L) and c.620G>A (p.R207H) from her father and mother, respectively. Presented here is a case of OI with inner ear deformation caused by c.620G>A (p.R207H), which is a novel WNT1 site mutation. This case broadens the genetic spectrum of OI and it provides a rationale for genetic testing of mothers and a medical consultation to estimate the risk of fetal illness.

[Distribution Characteristics and the Influencing Factors of High Altitude Deterioration in People Working in Tibet]. / è¥¿è—è‡ªæ²»åŒºåœ¨èŒèŒå·¥é«˜åŽŸè¡°é€€ç—‡çš„åˆ†å¸ƒç‰¹å¾åŠå½±å“å› ç´ .

Objective: To comprehensively investigate and analyze the distribution characteristics of high altitude deterioration (HADT) among people working in 7 cities of Tibet Autonomous Region, to examine the relevant influencing factors, and to provide baseline survey data for further research on HADT. Methods: A self-designed questionnaire was used to conduct a self-administered survey among employees in seven prefectures or cities (Lhasa City, Qamdo City, Shigatse City, Nyingchi City, Shannan City, Naqu City, and Ngari Prefecture) in Tibet. The respondents were selected through random cluster sampling. The survey covered 21 symptoms involving 4 systems of the human body, including the respiratory, nervous, circulatory, and digestive systems. The distributive characteristics of HADT (as manifested by maladaptation to high altitude) were described and Spearman's correlation was used to examine the influencing factors of maladaptation to high altitude. Results: A total of 3 901 respondents were included in the sample analyzed in the study, including 2 107 (54%) native Tibetans and 1 794 (46%) immigrant Han people. There were 1 994 males (51%) and 1 907 females (49%). Their age ranged from 20 to 57 years, averaging (34.45±8.11) years. The subjects lived at a high altitude for a duration of 0.5 to 54 years, averaging (19.51±13.84) years. The overall rates of maladaptation for the 21 symptoms among native Tibetans and immigrant Han people were 60.10% (26 578/44 247) and 73.20% (27 565/37 674), respectively. The maladaptation rates of the native Tibetan population for the respiratory, nervous, circulatory, and digestive systems of the human body were all lower than those of the immigrant Han population (P<0.001). There were no significant differences in the maladaptation rates of employees from different regions of Tibet (66.21% for Ngari Prefecture, 65.02% for Qamdo City, 66.67% for Lhasa City, 62.29% for Shigatse City, 65.03% for Shannan City, 64.42% for Nyingchi City, and 61.65% for Naqu City). The type of high-altitude residents (i.e., being native Tibetan or immigrant Han) was the main influencing factor for high-altitude maladaptation of the respiratory, nervous, circulatory, and digestive systems (P<0.001). According to the findings of the correlation analysis, age, type of high-altitude residents, and the duration of residence at a high altitude were associated with high-altitude maladaptation of the respiratory system, while type of high-altitude residents was the only factor associated with maladaptation of the nervous system, circulatory system, and digestive systems. Age and duration of living at at high altitude had significant effect on self-perceived dyspnea, a type of maladaptation of the respiratory system (P<0.001). Duration of high-altitude residence had significant effect on cyanotic lips or redness in the cheeks, a type of maladaptation of the circulatory system, and self-perceived loss of appetite, a type of maladaptation of the digestive system (P<0.05). Conclusion: More attention should be given to the HADT among employees of public institutions and enterprises who are living in Tibet Autonomous Region and immigrant Han people, in particular, should pay special attention to the protection of their respiratory, nervous, circulatory, and digestive systems.

Low serum transthyretin levels predict stroke-associated pneumonia.

BACKGROUND AND AIMS: Stroke-associated pneumonia (SAP) is commonly seen in ischemic stroke patients. Low transthyretin levels are found to be correlated with stroke. This study aims to investigate the potential relationship between transthyretin levels and SAP. METHODS AND RESULTS: In total, 920 patients were involved in our study. Serum transthyretin levels were measured within 24 h at admission. We defined SAP according to the modified Centers for Disease Control criteria. In the study population, 123 (13.4%, 77 men, 46 women) were diagnosed with SAP. In the multivariable analysis, we found that serum transthyretin levels were significantly lower in SAP compared with non-SAP patients (231 ± 80 vs. 279 ± 75; P < 0.001) after adjusting for confounders. Meanwhile, we discovered that low transthyretin levels (≤252 mg/L) were independently associated with the development of SAP (OR 3.370; 95% CI: 1.763-6.441; P < 0.001). Moreover, patients with SAP had a worse clinical outcome than those without SAP at discharge. In addition, dysphagia, leukocyte count and NLR (neutrophil-to-lymphocyte ratio) were also found to be associated with SAP. CONCLUSION: We found that low transthyretin levels significantly increased the risk of SAP. Patients with high risk of developing SAP could be early identified and prevented timely.

Investigating the effects of biochar colloids and nanoparticles on cucumber early seedlings.

Understanding about the influence of biochar colloidal and nanoscale particles on plant is limited. We therefore extracted the colloids and nanoparticles from hot pepper stalk biochar (CB600 and NB600), and examined physiological responses of cucumber early seedlings through hydroponic culture and pot experiment. CB600 had no significant effect on shoot at 500 mg/L, while it decreased root biomass and inhibited lateral root development. The biomass and root length, area, and tip number dramatically reduced after 500 mg/L NB600 treatment. Water content of NB600-exposed shoot was lower, suggesting water uptake and transfer might be hindered. For resisting exposure stress, root hair number and length increased. Even, the study observed swelling and hyperplasia of root hairs after direct exposure of CB600 and NB600. These adverse effects might be associated with the contact and adhesion of CB600 and NB600 with sharp edges to root surface. For a low concentration of 50 mg/L, NB600 did not influence cucumber early seedlings. In soil, CB600 and NB600 did not cause inhibitory effect at relatively high contents of 500 mg/kg and 2000 mg/kg. This study provides useful information for understanding phytotoxicity and environmental risk of biochar colloids and nanoparticles, which has significant implications with regard to biochar application safety.

Corrigendum: Age-Dependent Association Between Elevated Homocysteine and Cognitive Impairment in a Post-stroke Population: A Prospective Study.

[This corrects the article DOI: 10.3389/fnut.2021.691837.].

Age-Dependent Association Between Elevated Homocysteine and Cognitive Impairment in a Post-stroke Population: A Prospective Study.

Background and Purpose: The results regarding the independent association between homocysteine (Hcy) levels and post-stroke cognitive impairment (PSCI) were inconsistent. The effect of age on this association has yet to be explored. This study aims to determine the relationship between Hcy levels, age, and cognitive impairment in a post-stroke population. Methods: A total of 592 patients with acute ischemic stroke (AIS) completed follow-up. Serum Hcy levels were measured enzymatically by spectrophotometry within 24 h of admission. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE) 1 month after stroke, and the scores ≤ 24 were considered as cognitive impairment. Our study was dichotomized into two groups by a cut-off of 65 years. Multivariate logistic regression models were used to determine the association between baseline Hcy levels and cognitive impairment. Results: According to the MMSE score, 317 (53.5%) patients had cognitive impairment. Patients with higher levels of Hcy were more prone to have cognitive impairment 1 month after stroke than patients with lower levels of Hcy (p < 0.001). The optimal cut-off points of Hcy level (µmol/L) were (T1) ≤ 8, (T2) 8-12, and (T3) ≥ 12. After adjusting for confounding factors, the multivariate regression analysis showed that the third Hcy tertile was independently associated with cognitive impairment [odds ratio (OR) = 2.057, 95% confidence interval (CI) = 1.133-3.735, p = 0.018). A stronger association [T2 (OR = 2.266, 95% CI = 1.042-4.926, p = 0.039); T3 (OR =3.583, 95% CI = 1.456-8.818, p = 0.005)] was found in the younger group. However, the independent association was not confirmed in the older group. Conclusions: Elevated Hcy levels in the acute phase of ischemic stroke were independently associated with cognitive impairment in a post-stroke population. Furthermore, the association was age-dependent and more meaningful in a younger population aged below 65. So, Hcy levels in patients with stroke should be well-monitored, especially in younger patients.

Chromatin remodeler ARID1A binds IRF3 to selectively induce antiviral interferon production in macrophages.

Transcription factor IRF3 is critical for the induction of antiviral type I interferon (IFN-I). The epigenetic regulation of IFN-I production in antiviral innate immunity needs to be further identified. Here, we reported that epigenetic remodeler ARID1A, a critical component of the mSWI/SNF complex, could bind IRF3 and then was recruited to the Ifn-I promoter by IRF3, thus selectively promoting IFN-I but not TNF-α, IL-6 production in macrophages upon viral infection. Myeloid cell-specific deficiency of Arid1a rendered mice more susceptible to viral infection, accompanied with less IFN-I production. Mechanistically, ARID1A facilitates chromatin accessibility of IRF3 at the Ifn-I promoters by interacting with histone methyltransferase NSD2, which methylates H3K4 and H3K36 of the promoter regions. Our findings demonstrated the new roles of ARID1A and NSD2 in innate immunity, providing insight into the crosstalks of chromatin remodeling, histone modification, and transcription factors in the epigenetic regulation of antiviral innate immunity.

[Spatio-temporal Patterns and Potential Sources of Absorbing Aerosols in the Fenwei Plain].

Air quality has gradually improved in many parts of China; however, air pollution is become more severe in the Fenwei Plain. Using OMI/Aura OMAERUV L2 and PM2.5 data, spatial autocorrelation analysis and back trajectory modeling were used to explore the spatio-temporal patterns of absorptive aerosols over the Fenwei Plain, and the dominant types, transmission paths, and potential source areas were identified. The main results can be summarized as follows:① Annual mean absorbing aerosol index (AAI) values increased between 2005 and 2019, with high period occurring in 2006, 2013, and 2017, with values exceeding 0.63. Xi'an and Linfen were identified as a 'high-high' cluster, with AAI showing poor spatial stability and a 15.3% increase in area over the past 15 years. In contrast, the area connecting Xi'an and Linfen, which occupies 24.2% of the total area of the region, was identified as a 'low-low' cluster, with a sharp drop of 6.2% in area; ② The Fenwei Plain has high AAI values across a large area in winter, exceeding 0.8 in Linfen and Xi'an, and 91.5% of the study area exceeding 0.6. Values were lower in spring (AAI>0.4) and autumn (AAI>0.3), with the lowest values occurring in summer. The atmospheric diffusion conditions in spring, autumn, and winter are poor, associated with anticyclonic high-pressure events. The observed high AAI values were significantly affected by atmospheric diffusion conditions, temperature, and precipitation; ③ Back trajectory and source contribution modeling showed that long-range transport of air masses from Xi'an and Linfen occurs from the northwest, and short-range transport air masses occurs from the east and south. Two long-range sand and dust source areas were determined (with northwestern and northern wind sources); two carbon source areas were identified (with eastern and southern wind sources); and one combined sand and carbon source area was identified (from the Loess Plateau). Of these sources, the northwestern wind source, the Loess Plateau, and the southern wind source have significant influence in Xi'an, and the eastern wind source and the Loess Plateau have a significant impact on Linfen. Linfen is little affected by the northwestern wind source and the dust from the northern wind source. Based on the spatial distribution of CO and its correlation with AAI, it is concluded that cardon in the dominant absorbent aerosol in Linfen dust and carbon are most important in Xi'an.

Influence of Poly(ethylene glycol) Molecular Architecture on Particle Assembly and Ex Vivo Particle-Immune Cell Interactions in Human Blood.

Poly(ethylene glycol) (PEG) is widely used in particle assembly to impart biocompatibility and stealth-like properties in vivo for diverse biomedical applications. Previous studies have examined the effect of PEG molecular weight and PEG coating density on the biological fate of various particles; however, there are few studies that detail the fundamental role of PEG molecular architecture in particle engineering and bio-nano interactions. Herein, we engineered PEG particles using a mesoporous silica (MS) templating method and investigated how the PEG building block architecture impacted the physicochemical properties (e.g., surface chemistry and mechanical characteristics) of the PEG particles and subsequently modulated particle-immune cell interactions in human blood. Varying the PEG architecture from 3-arm to 4-arm, 6-arm, and 8-arm generated PEG particles with a denser, stiffer structure, with increasing elastic modulus from 1.5 to 14.9 kPa, inducing an increasing level of immune cell association (from 15% for 3-arm to 45% for 8-arm) with monocytes. In contrast, the precursor PEG particles with the template intact (MS@PEG) were stiffer and generally displayed higher levels of immune cell association but showed the opposite trend-immune cell association decreased with increasing PEG arm numbers. Proteomics analysis demonstrated that the biomolecular corona that formed on the PEG particles minimally influenced particle-immune cell interactions, whereas the MS@PEG particle-cell interactions correlated with the composition of the corona that was abundant in histidine-rich glycoproteins. Our work highlights the role of PEG architecture in the design of stealth PEG-based particles, thus providing a link between the synthetic nature of particles and their biological behavior in blood.

Anti-Oxidative and Immuno-Protective Effect of Camel Milk on Radiation-Induced Intestinal Injury in C57BL/6 J Mice.

PURPOSE: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury. METHODS: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors. RESULTS: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1ß and increased IL-10 level. CONCLUSIONS: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.

Individualized predictions of early isolated distal deep vein thrombosis in patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. METHODS: This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. RESULTS: The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. CONCLUSIONS: The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.

High Fibrinogen to Albumin Ratio: A Novel Marker for Risk of Stroke-Associated Pneumonia?

Background: Stroke-associated pneumonia (SAP) is associated with poor prognosis after acute ischemic stroke (AIS). Purpose: This study aimed to describe the parameters of coagulation function and evaluate the association between the fibrinogen-to-albumin ratio (FAR) and SAP in patients with AIS. Patients and methods: A total of 932 consecutive patients with AIS were included. Coagulation parameters were measured at admission. All patients were classified into two groups according to the optimal cutoff FAR point at which the sum of the specificity and sensitivity was highest. Propensity score matching (PSM) was performed to balance potential confounding factors. Univariate and multivariate logistic regression analyses were applied to identify predictors of SAP. Results: A total of 100 (10.7%) patients were diagnosed with SAP. The data showed that fibrinogen, FAR, and D-dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT) were higher in patients with SAP, while albumin was much lower. Patients with SAP showed a significantly increased FAR when compared with non-SAP (P < 0.001). Patients were assigned to groups of high FAR (≥0.0977) and low FAR (<0.0977) based on the optimal cut-off value. Propensity score matching analysis further confirmed the association between FAR and SAP. After adjusting for confounding and risk factors, multivariate regression analysis showed that the high FAR (≥0.0977) was an independent variable predicting the occurrence of SAP (odds ratio =2.830, 95% CI = 1.654-4.840, P < 0.001). In addition, the FAR was higher in the severe pneumonia group when it was assessed by pneumonia severity index (P = 0.008). Conclusions: High FAR is an independent potential risk factor of SAP, which can help clinicians identify high-risk patients with SAP after AIS.

High Monocyte-To-Lymphocyte Ratio Is Associated With Stroke-Associated Pneumonia.

Purpose: Stroke-associated pneumonia (SAP), a common complication in acute ischemic stroke (AIS) patients, is associated with poor prognosis after AIS. Inflammation plays an important role in the development of SAP. In this study, we aimed to explore the association between the monocyte-to-lymphocyte ratio (MLR) and SAP in AIS patients. Methods: We continuously enrolled 972 AIS patients. SAP was diagnosed by two trained neurologists and confirmed by radiography, meeting the modified Centers for Disease Control and Prevention criteria. MLR values were measured for all participants, and all patients were evenly classified into three tertiles according to the MLR levels. We used the values that Youden's index max points corresponded to represent the optimal cutoffs, which represented the balance in sensitivity and specificity. Results: 104 (10.7%) patients were diagnosed with SAP. SAP patients showed a significant increased (P < 0.001) MLR when compared with non-SAP. The optimal cutoff points of MLR were (T1) <0.2513, (T2) 0.2513-0.3843, and (T3) > 0.3843. The incidence of SAP was significantly higher in the third MLR tertile than the first and second MLR tertiles (21.7 vs. 4 vs. 6.5%, respectively, P < 0.001). After adjusting for confounding and risk factors, multivariate regression analysis showed that the third MLR tertile was an independent variable predicting the occurrence of SAP (odds ratio = 3.503, 95%CI = 1.066-11.515, P = 0.039). Conclusions: Our study showed that higher MLR was significantly associated with SAP in AIS patients. MLR is beneficial for clinicians to recognize patients with a high risk of SAP at an early stage and is an effective way to improve clinical care of SAP patients. Higher MLR could be a helpful and valid biomarker for predicting SAP in clinical practice.