Role of Peptidyl arginine deiminase 4-dependent macrophage extracellular traps formation on Type 1 Diabetes pathogenesis.

Excessive macrophage extracellular traps (METs) formation has been implicated in several autoimmune disease pathogenesis; however, its impact on Type 1 Diabetes (T1D) and related mechanisms remains enigmatic. Here, we demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse METs formation and macrophage M1 polarization in intestinal inflammation of non-obese diabetic (NOD) mice. Genetic knockout of PAD4 or adoptive transfer of METs alters the proportion of pro-inflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated METs formation in the colon increases the aggravation of intestinal inflammation and pro-inflammatory T cells migration, and finally involves T1D progression, suggesting that inhibition METs formation may be a potential therapeutic target for T1D.

Developing a nomogram for predicting acute complicated course in pediatric acute hematogenous osteomyelitis.

BACKGROUND: The objective of this study was to develop and validate a nomogram for predicting the risk of an acute complicated course in pediatric patients with Acute Hematogenous Osteomyelitis (AHO). METHODS: A predictive model was developed based on a dataset of 82 pediatric AHO patients. Clinical data, imaging findings, and laboratory results were systematically collected for all patients. Subsequently, biomarker indices were calculated based on the laboratory results to facilitate a comprehensive evaluation. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing early adverse outcomes in AHO. A nomogram model was constructed based on independent factors and validated internally through bootstrap methods. The discriminative ability, calibration, and clinical utility of the nomogram model were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), respectively. The developed nomogram model was compared with previously published A-score and Gouveia scoring systems. RESULTS: Logistic regression analysis identified delayed source control, suppurative arthritis, albumin on admission, and platelet to lymphocyte ratio (PLR) as independent predictors of early adverse outcomes in pediatric AHO patients. The logistic regression model was formulated as: Log(P) = 7. 667-1.752 × delayed source control - 1.956 × suppurative arthritis - 0.154 × albumin on admission + 0.009 × PLR. The nomogram's AUC obtained through Bootstrap validation was 0.829 (95% CI: 0.740-0.918). Calibration plots showed good agreement between predictions and observations. Decision curve analysis demonstrated that the model achieved net benefits across all threshold probabilities. The predictive efficacy of our nomogram model for acute complicated course in pediatric AHO patients surpassed that of the A-score and Gouveia scores. CONCLUSIONS: A predictive model for the acute complicated course of pediatric AHO was established based on four variables: delayed source control, suppurative arthritis, albumin on admission, and PLR. This model is practical, easy to use for clinicians, and can aid in guiding clinical treatment decisions.

COMBINATION OF HYPEROXYGENATION AND TARGETED TEMPERATURE MANAGEMENT IMPROVES FUNCTIONAL OUTCOMES OF POST CARDIAC ARREST SYNDROME IRRESPECTIVE OF CAUSES OF ARREST IN RATS.

ABSTRACT: Background: The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA. Methods and Results: One hundred sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: normoxia-normothermia (NO-NT), ventilated with 21% oxygen under normothermia; hyperoxia-normothermia (HO-NT), ventilated with 100% oxygen for 3 hours under normothermia; normoxia-hypothermia (NO-HT), ventilated with 21% oxygen for 3 hours under hypothermia; and hyperoxia-hypothermia (HO-HT), ventilated with 100% oxygen for 3 hours under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed. For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7% ± 14.9% and 40.3% ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0% ± 5.7% and 28.0% ± 13.3%) were significantly reduced. Conclusion: The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial, whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.

Hydrogen sulfide donors across time: From origins to cutting-edge applications.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

Molecular Investigation and Preliminary Validation of Candidate Genes Associated with Neurological Damage in Heat Stroke.

Heat stroke (HS) is a severe medical condition characterized by a systemic inflammatory response that may precipitate multi-organ dysfunction, with a particular predilection for inducing profound central nervous system impairments. We aim to employ bioinformatics techniques for the retrieval and analysis of genes associated with heat stroke-induced neurological damage. We performed a comprehensive analysis of the GSE64778 dataset from the Sequence Read Archive, resulting in the identification of 1178 significantly differentially expressed genes (DEGs). We retrieved 2914 genes associated with heat stroke from the GeneCards database and 2377 genes associated with heat stroke from the Comparative Toxicogenomics Database (CTD). The intersection of the top 300 DEGs in the GSE64778 dataset intersected with the search results of GeneCards and CTD, yielding 25 final candidates for DEGs associated with heat stroke. Gene Ontology functional annotation results indicated that the target genes were mainly involved in apoptosis, stress response, and negative regulation of cellular processes and function in processes such as protein dimerization and protein binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed a predominant enrichment of candidate target genes within the PI3K-AKT signaling pathway. Subsequent protein-protein interaction network analysis highlighted HSP90aa1 as a central gene, indicating its pivotal role by possessing the highest number of edges among the genes enriched in the PI3K-AKT signaling pathway. Quantitative reverse transcription-polymerase chain reaction analysis performed on blood samples from patients validated the expression of Hsp90aa1 in individuals exhibiting early neurological damage in HS, consistent with the findings from the mRNA bioinformatics analysis. Additionally, the bioinformatics analysis of the upstream microRNAs (miRNAs) regulating HSP90aa1 and the target miRNAs associated with candidate long non-coding RNAs (lncRNAs) identified three lncRNAs, eight miRNAs, and one mRNA in the regulatory network. The DIANA Tools database and algorithms were employed for pathway enrichment and correlation analysis, revealing a significant association between LOC102547734 and MIR-206-3p, with the latter being identified as a target binding site Moreover, the analysis unveiled a correlation between MIR-206-3p and HSP90aa1, implicating the latter as a potential target binding site within the regulatory network.

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system.

BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.

SIGANEO: Similarity network with GAN enhancement for immunogenic neoepitope prediction.

Target selection of the personalized cancer neoantigen vaccine, which is highly dependent on computational prediction algorithms, is crucial for its clinical efficacy. Due to the limited number of experimentally validated immunogenic neoepitopes as well as the complexity of neoantigens in eliciting T cell response, the accuracy of neoepitope immunogenicity prediction methods requires persistent efforts for improvement. We present a deep learning framework for neoepitope immunogenicity prediction - SIGANEO by integrating GAN-like network with similarity network to address issues of missing values and limited data concerning neoantigen prediction. This framework exhibits superior performance over competing machine-learning-based neoantigen prediction algorithms over an independent test dataset from TESLA consortium. Particularly for the clinical setting of neoantigen vaccine where only the top 10 and 20 predictions are selected for vaccine production, SIGANEO achieves significantly better accuracy for predicting experimentally validated neoepitopes. Our work demonstrates that deep learning techniques can greatly boost the accuracy of target identification for cancer neoantigen vaccine.

Identification and validation of a novel signature based on T cell marker genes to predict prognosis, immunotherapy response and chemotherapy sensitivity in head and neck squamous carcinoma by integrated analysis of single-cell and bulk RNA-sequencing.

T cells are among the most potent anti-tumor cells that are found in humans. Our study sought to develop a reliable signature incorporating T cell marker genes (TMGs) for predicting the prognosis and therapy responsiveness of head and neck squamous cell carcinoma (HNSCC) patients. We downloaded scRNA-seq data from the GSE181919 to identify TMGs. Subsequently, we devised a 12 TMG signature in the TCGA HNSCC cohort by using LASSO analysis. Patients with high-risk scores were shown to experience unfavorable progression-free survival, disease-specific survival, and overall survival, which was validated in the GSE65858 cohort. Additionally, the nomogram integrated risk score and clinical features are more suitable for clinical application. The enrichment analyses of both pathways and functions showed that high- and low-risk patients had functionally related distinctions. Furthermore, analysis of the immunological landscape confirmed that the low-risk patients had a larger percentage of infiltrating immune cells as well as a higher incidence rate of immune-related events. In the meantime, a greater IPS score and expression of immune checkpoint genes suggested significantly favorable responsiveness to immunotherapy in low-risk patients. On the other hand, the high-risk patients had a greater degree of sensitivity to the chemotherapy agents, which included paclitaxel, gemcitabine, docetaxel, and cisplatin. Our finding revealed that this TMG signature independently functioned as a prognostic marker and guided individualized immunotherapy and chemotherapy selection for patients with HNSCC.

EVOO supplement prevents type 1 diabetes by modulating gut microbiota and serum metabolites in NOD mice.

AIMS: Extra virgin olive oil (EVOO) is the highest quality olive oil available and has been shown to regulate postprandial blood glucose in patients with type 1 diabetes (T1D). However, it remains uncertain whether EVOO can prevent the onset of T1D. In this study, we investigated the potential preventive effect of orally administered EVOO on T1D in non-obese diabetic (NOD) mice. MAIN METHODS: We analyzed changes in fecal microbes using 16 s rDNA sequencing and serum metabolites using Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Mass Spectrometry (Q-TOF-MS). KEY FINDINGS: Our findings showed that EVOO supplementation in NOD mice slowed gastric emptying, reduced insulitis, and delayed T1D onset. Moreover, EVOO altered the composition of fecal microbes, increasing the Bacteroidetes/Firmicutes ratio, and promoting the growth of short-chain fatty acids (SCFAs)-producing bacteria, such as Lachnoclostridium and Ruminococcaceae_UCG-005. Moreover, it also increased beneficial serum metabolites, including unsaturated fatty acid and triterpenoid, which positively correlated with the increased SCFA-producing bacteria and negatively correlated with the disease indicators. Conversely, most decreased serum lipid metabolites, such as Oleamide, showed the opposite trend. SIGNIFICANCE: Our study demonstrates that EVOO may ameliorate pancreas inflammation and prevent T1D onset in NOD mice by modulating gut microbiota and serum metabolites.

[Rapid determination of 13 ß-blockers in health foods by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry].

A method based on ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry was developed for the rapid determination of 13 ß-blockers in health foods. The MS fragmentation pathways of the analytes were subsequently investigated. The optimal MS conditions, extraction solvents, mobile phases, and matrix effects were evaluated in detail. The samples were extracted with methanol, filtered by high-speed centrifugation and ultrasonic treatment, and then separated on an Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) with gradient elution using acetonitrile and 0.1% (v/v) formic acid aqueous solution as mobile phases. MS analysis was conducted in positive-ion mode, and the data were collected using full mass and data-dependent MS2 scans (Full MS/dd-MS2). The efficient separation and high-precision primary and secondary scanning of the 13 ß-blockers in health foods were realized within 10 min, and accurate mass numbers and fragment-ion information were obtained. The methodological validation showed good linear relationships in the range of 0.5-100 µg/L, with correlation coefficients (r)≥0.9912. The limits of detection ranged from 1 to 10 µg/kg. When the standard substances were added to the blank sample in the amount of 10-200 µg/kg, the recoveries were in the range of 75.3%-108.4%, and the relative standard deviations ranged from 0.9% to 10.0% (n=6). The method was used to screen 30 batches of commercially available health foods, and none of the 13 ß-blockers was detected. The proposed method is fast, accurate, and sensitive, and can be used for the rapid determination of ß-blockers in health foods.

Establishment and validation of an AI-aid method in the diagnosis of myocardial perfusion imaging.

BACKGROUND: This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. METHODS: We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named "YOLO" to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). RESULTS: Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value < 0.05). CONCLUSION: The AI system of our study showed excellent predictive accuracy in the diagnosis of MPI protocols, and therefore might be potentially helpful to aid radiologists in clinical practice and develop more sophisticated models.

Impacts of different reconstruction methods on the image quality of cadmium-zinc-telluride-based single photon emission computed tomography/computed tomography pulmonary perfusion imaging.

OBJECTIVE: The objective was to evaluate the impacts of different reconstruction methods [filtered back projection (FBP) and ordered subset expectation maximization (OSEM)] and different filters (Butterworth filter and Gaussian filter) on the image quality in cadmium-zinc-telluride (CZT)-based single photon emission computed tomography (SPECT)/computed tomography (CT) pulmonary perfusion imaging. METHODS: A combinations including FBP with Butterworth filter, OSEM with Butterworth filter (OSEM + Butterworth filter ), and OSEM with Gaussian filter (OSEM + Gaussian filter) were used during SPECT image reconstruction. Visual and quantitative parameters [root mean square (RMS) noise, contrast and contrast-to-noise ratio (CNR)] were used to evaluate image quality. RESULTS: The OSEM + Gaussian filter had better RMS noise and CNR than those of the FBP + Butterworth filter or OSEM + Butterworth filter, while the OSEM + Butterworth filter had the best contrast. The highest visual scores were obtained by OSEM + Gaussian filter ( P  < 0.0001). In the lesion size <2 cm group, the contrast ( P < 0.01) and visual scores ( P < 0.001) of OSEM + Butterworth filter were better than those of the other two groups. In the lesion size ≥2 cm group, the RMS noise and visual scores of OSEM + Gaussian filter were better than those of the other two groups. CONCLUSION: In CZT SPECT/CT pulmonary perfusion imaging, this study recommended the clinical use of the OSEM + Gaussian filter combination for reconstruction in both conventional and larger lesions, the OSEM + Butterworth filter image postprocessing method might be advantageous in small lesions.

The role of protein arginine deiminase 4-dependent neutrophil extracellular traps formation in ulcerative colitis.

Background: Neutrophil extracellular traps (NETs) play an important role in the development and progression of ulcerative colitis (UC). Peptidyl arginine deiminase 4 (PAD4) is essential for the formation of NETs via catalyzing histone citrullination. This study mainly to explore the role of PAD4-mediated NETs in intestinal inflammation of dextran sulfate sodium (DSS)-induced UC. Methods: Acute and chronic colitis mouse models were established by supplementing DSS in drinking water. Colon tissues from colitis mice were analyzed for the level of PAD4 expression, citrullinated histone H3(Cit-H3), intestinal histopathology, and inflammatory cytokines secretion. Serum samples were tested for systemic neutrophil activation biomarkers. Colitis mice administered with Cl-amidine, a PAD4 inhibitor, and PAD4 knockout mice were investigated to detect NETs formation, intestinal inflammation, and barrier function. Result: We found the formation of NETs significantly increased in DSS-induced colitis mice and was correlated with disease markers. Blocking NETs formation by Cl-amidine or PAD4 genetic knockout could alleviate clinical colitis index, intestinal inflammation, and barrier dysfunction. Conclusion: This study provided a research basis for the role of PAD4-mediated NETs formation in the pathogenesis of UC and suggested that inhibition of PAD4 activity and the formation of NETs may be helpful for the prevention and treatment of UC.

The clinical characteristics of pancreatic colloid carcinoma and the development and validation of its cancer-specific survival prediction nomogram.

Background: Pancreatic colloid carcinoma (CC) is a subtype of pancreatic ductal adenocarcinoma (DAC) with low incidence but high malignancy. Unfortunately, there is no consensus regarding the clinical features and prognostic factors associated with CC, and the prognosis is unpredictable. We aimed to assess the clinicopathological characteristics of this rare disease and develop a nomogram for predicting cancer-specific survival (CSS) in CC. Methods: We gathered comprehensive clinicopathological data from the Surveillance, Epidemiology, and End Results (SEER) database on 17,617 patients with DAC and 561 individuals with CC. Kaplan-Meier was used to plot each survival curve. Subsequently, we split the 561 patients with CC in a 7:3 split ratio between an internal training cohort (n=393) and an external validation cohort (n=168). The independent prognostic factors for CC patients in the training cohort were discovered using univariate and multivariate Cox regression analyses, and a nomogram was created. We assessed the nomogram's performance by using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Results: The median for follow-up of CC patients was 15 months (range: 1-163 months), and the 1-, 3-, and 5-year CSS were 58.4%, 30.2% and 22.6%. For CC patients in the training cohort, age [hazard ratio (HR) =1.29; 95% confidence interval (CI): 1.00-1.65], sex (HR =0.64; 95% CI: 0.51-0.81), T3 stage (HR =2.21; 95% CI: 1.26-3.88), T4 stage (HR =2.76; 95% CI: 1.47-5.18), N1 stage (HR =1.29; 95% CI: 1.02-1.63), M1 stage (HR =1.60; 95% CI: 1.17-2.18), surgery (HR =0.30; 95% CI: 0.22-0.42), and radiotherapy (HR =0.76; 95% CI: 0.58-1.01) were the main predictors of the nomogram. The C-indexes of the training cohort and the validation cohort were 0.734 and 0.732, respectively. The 1-, 3-, and 5-year AUC values of the nomogram were predicted to be 0.827, 0.816, and 0.831 in the training cohort, 0.801, 0.841, and 0.835 in the validation cohort, respectively. Conclusions: Based on several clinical features, we established the first predictive model of CC. This nomogram could be used to guide treatment decisions in patients with CC.

Strategical development of chrome-free tanning agent by integrating layered double hydroxide with starch derivatives.

The development of sustainable and eco-friendly leather industry requires green tanning agents because of unbounded chromium (easily converted into hazardous Cr-VI) in chrome tanned leather. In this study, a chrome-free tanning agent (OS-LDHs) was established by integrating layered double hydroxide (magnesium aluminum zirconium hydrotalcite, LDHs) with starch derivatives. A series of oxidized starch (OS) were prepared as masking agents for LDHs tanning process. Among them, the weight-average molecular weight (Mw) of 1685 g/mol could be reached, which will promise the well-distribution of OS. The SEM and EDS analysis confirmed the uniform penetration of OS-LDHs, avoiding accumulation on the surface of crust leather. Notably, leather tanned by OS-LDHs achieved shrinkage temperature of 66.7 °C, porosity of 75.51 % and tear strength of 66.7 N/mm. Not only the hydrogen bond but also the coordination between NH2, COOH in collagen and OS-2-LDHs improved the thermal stability of leather without destroying the collagen triple helix.

Diagnostic Significance of Combined Calcitoninogen, Platelet, and D-Dimer Assay in Severe Heatstroke: with Clinical Data Analysis of 70 Patients with Severe Heatstroke.

The significance of calcitoninogen detection among inpatients was discussed by analyzing the clinical characteristics of severe heatstroke (HS). HS patients who were admitted to the Second Hospital of Nantong University, Jiangsu Province, China, between July 1, 2015, and October 30, 2020, were reviewed. Patients' clinical characteristics and laboratory data were recorded, and they were divided into three groups, that is, a control group (heat cramps and heat exhaustion), an exertional HS (EHS) group, and a classical HS (CHS) group to compare the differences among them. Receiver operating characteristic (ROC) curves were plotted to evaluate patients' clinical utility. (1) The body temperatures in the EHS and CHS groups were significantly higher than in the control group (all p < 0.05). (2) The D-dimer (DD), procalcitonin (PCT), and Acute Physiology and Chronic Health Evaluation (APACHE) II score of the EHS group were significantly higher compared with the control and CHS groups (all p < 0.05); the platelets (PLT), C-reactive protein (CRP), blood sodium (Na), and intravenous glucose (GLU) of the EHS group were lower than in the control and CHS groups (all p < 0.05). (3) The ROC curve analysis showed the performance results for DD (area under the curve [AUC] 0.670, 95% confidence interval [CI] 0.547-0.777), PCT (AUC 0.705, 95% CI 0.584-0.808), and PLT (AUC 0.791, 95% CI 0.677-0.879). The sensitivity was 40.48%, 100%, and 73.81%, and the specificity was 96.43%, 32.14%, and 78.57%, respectively. Using three combined analyses, an elevated AUC of 0.838, 95% CI 0.731-0.916, with a sensitivity of 71.43% and a specificity of 85.71%, respectively, was revealed. Patients in the EHS group had higher DD, PCT, and APACHE II values, whereas PLT, CRP, Na, and GLU were reduced. The apparent decrease in the PLT, as well as the increase in PCT and DD values, could be considered as early sensitivity indicators of severe HS. A combined test of these three indicators presented significant diagnostic value for detecting severe cases of HS.

Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest.

Background: Post-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF). Methods: Cardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague-Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half. Results: No statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014). Conclusion: In this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.

Femtosecond laser writing of waveguides in zinc oxide crystals: fabrication and mode modulation.

We report for the first time on optical waveguides in zinc oxide (ZnO) crystals fabricated by femtosecond laser direct writing. The confocal Raman microscopy under 488 nm laser excitation is used to investigate the micro-modifications of the laser irradiation, and guiding properties are studied via the end-face coupling at 632.8 nm. The mode modulation has been achieved by the adjustment of laser writing parameters. A minimum propagation loss of ∼6 dB/cm is obtained for the double-line waveguide structures. A Y-branch waveguide beam splitter is also fabricated, reaching a splitting ratio of nearly 1:1. The original optical properties in the guiding region have been well preserved, according to the confocal Raman investigation, which suggests potential applications of the ZnO waveguides for integrated photonics and nonlinear optics.

Radionuclide 131I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer.

Objectives: Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC. Methods: 131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels. Results: The synthesized nanoparticles had a suitable size (25-45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4-6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser. Conclusions: In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.

Expression profile and prognostic value of CXCR family members in head and neck squamous cell carcinoma.

BACKGROUND: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). METHODS: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features, and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). RESULTS: CXCRs were differentially expressed in HNSCC. As shown by Kaplan-Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. CONCLUSIONS: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.