Detoxification of DON-induced hepatotoxicity in mice by cold atmospheric plasma.

Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma (CAP) has received much attention in mycotoxin degradation due to the advantages of easy operation, high efficiency, and low temperature. So far, the majority of studies have focused on the degradation efficiency and mechanism of CAP on DON, while there is still little information available on the hepatotoxicity of DON after CAP treatment. Herein, this study aimed to investigate the effect of CAP on DON-induced hepatotoxicity both in vitro and in vivo and its underlying mechanisms. The results showed that 120-s CAP treatment achieved 97 % degradation of DON. The vitro hepatotoxicity of DON in L02 cells was significantly reduced with CAP treatment time. Meanwhile, CAP markedly alleviated DON-induced liver injury in mice including the balloon-like degeneration of liver tissues and elevation of AST and ALP level. The underlying mechanism for CAP detoxification of DON-induced hepatotoxicity was further elucidated. The results showed that DON caused severe oxidative stress in cells by suppressing the antioxidant signaling pathway of Nrf2/HO-1/NQO-1, consequently leading to mitochondrial dysfunction and cell apoptosis, accompanied by cellular senescence and inflammation. CAP blocked DON inhibition on the Nrf2/HO-1/NQO-1 signaling pathway through the efficient degradation of DON, accordingly alleviating the oxidative stress and liver injury induced by DON. Therefore, CAP is an effective method to eliminate DON hepatotoxicity, which can be applied in the detoxification of mycotoxin-contaminated food and feed to ensure human and animal health.

The diagnostic value of [18F]FAPI-42 PET/CT for pulmonary artery masses: comparison with [18F]FDG PET/CT.

OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

Prediction of clinical risk assessment and survival in chronic obstructive pulmonary disease with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

The effect of vitamin D deficiency during pregnancy on adverse birth outcomes in neonates: a systematic review and meta-analysis.

Objective: To systematically evaluate the effect of vitamin D deficiency during pregnancy on neonatal adverse outcomes, such as preterm infants, low birth weight infants (LBWI), and small for gestational age (SGA) infants. Methods: A comprehensive literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, SinoMed, Wanfang Data Knowledge Service Platform, China National Knowledge Internet (CNKI), and VIP Chinese Science and Technology Journal Database (VIP). Following predefined inclusion and exclusion criteria, two researchers independently screened, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 and Stata 14 software to synthesize the findings. Results: This study incorporated 13 cohort studies from 8 different countries and regions, encompassing a total of 55,162 pregnant women, among whom 28,155 were identified as having vitamin D deficiency. The Newcastle-Ottawa Scale (NOS) score ranged from 7-9 points. Meta-analysis results indicated a higher incidence of LBWI (OR = 5.52, 95% CI = 1.31-23.22. P = 0.02) in the group of pregnant women with vitamin D deficiency compared to those with adequate levels. However, there was no statistically significant difference in the likelihood of premature birth (OR = 1.25, 95% CI = 0.78-1.99. P = 0.36) or SGA (OR = 1.47, 95% CI = 0.81-2.68. P = 0.21) among newborns born to mothers with vitamin D deficiency vs. those with sufficient levels of vitamin D. Subgroup analysis based on the timing of maternal blood collection revealed that there was no statistically significant association between vitamin D levels during pregnancy and the incidence of preterm birth across all stages of pregnancy. Furthermore, vitamin D deficiency throughout the entire pregnancy was associated with an increased incidence of neonatal LBWI, whereas vitamin D levels during the first, second, and third trimesters did not demonstrate statistically differences on LBWI. Neonates born to mothers with vitamin D deficiency throughout pregnancy were found to have a higher likelihood of developing SGA. However, there was no statistically significant association between vitamin D levels and the development of SGA during the first and second trimesters. Conclusions: Adequate levels of vitamin D during pregnancy may decrease the incidence of LBWI, although further research is needed to determine its impact on the occurrence of preterm birth and SGA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024535950, Identifier: (CRD42024535950).

Protective Effect of CXCR7 Against Hypoxia/Reoxygenation Injury in Renal Tubular Epithelial Cells.

Acute kidney injury (AKI) is a multifactorial syndrome with complex pathophysiology and prognosis. Ischaemia‒reperfusion injury (IRI) is a major cause of induced AKI. The aim of this study was to investigate the effect of upregulated CXCR7 expression on renal tubular epithelial cell apoptosis induced by hypoxia/reoxygenation (H/R). HK-2 cells were divided into three groups: control group (pcDNA3.1), hypoxia/reoxygenation + pcDNA3.1 group (H/R+pcDNA3.1) and CXCR7 overexpression + hypoxia/reoxygenation group (H/R+ Flag-CXCR7). Protein levels of renal tubular epithelial cell injury-, apoptosis- and autophagy-related markers were assessed by qRT‒PCR, Western blotting, flow cytometry (FCM), immunofluorescence and transmission electron microscopy (TEM). In addition, HK-2 cells were treated with the autophagy inhibitor 3-MA and divided into 3 groups: control group, 3-MA + pcDNA3.1 group, and 3-MA + Flag-CXCR7 group. Changes in autophagy and apoptosis in renal tubule epithelial cells were assessed by Western blotting and FCM. Compared with those in the control group, the protein and mRNA expression levels of CXCR7 in HK-2 cells were significantly lower under H/R conditions. Under H/R conditions, CXCR7 overexpression in HK-2 cells significantly downregulated the expression of NGAL. Moreover, CXCR7 overexpression significantly decreased H/R-induced cleaved PARP-1 and cleaved Caspase 3 levels, increased the level of the antiapoptotic protein BCL-2 and the autophagy-related molecules ATG5 and LC3B II, and significantly inhibited the expression of P62. Autophagy flow and TEM also showed that CXCR7 significantly promoted autophagy. CXCR7 significantly alleviated the 3-MA-induced inhibition of autophagy and increase in apoptosis. Upregulated CXCR7 expression can inhibit renal tubular epithelial cell apoptosis and damage by regulating autophagy. In conclusion, CXCR7 is a promising target for the prevention and/or treatment of AKI.

Demand analysis of health care services for community-dwelling breast cancer survivors based on the Kano model: A cross-sectional study.

Objectives: Providing satisfactory healthcare services for breast cancer survivors can effectively reduce their burden and the pressure on medical resources. The aim of this study was to explore health care service demands for community-dwelling breast cancer survivors using the Kano model. Methods: A cross-sectional survey was conducted from January to March 2023 among breast cancer survivors discharged from a tertiary cancer hospital. Participants were asked to fill out a self-designed questionnaire involving the Kano model, which helped to categorize and prioritize the attributes of healthcare services. The questionnaire included 30 health care services. Additionally, their social demographic characteristics were collected during the survey. Results: A total of 296 valid questionnaires were collected, and demand attributes of the 30 health care services were evaluated. The findings revealed that one of 30 services was classified as "must-be attributes" (body image management), 13 as "one-dimensional attributes" (focused on medical security support, health management, and health counseling), 3 as "attractive attributes" (focused on communication needs and telehealth services), and 11 as "indifferent attributes" (mainly in the area of psycho-social services). Conclusions: Breast cancer survivors in the community have different levels of need for various health care services. It's crucial for healthcare providers to identify these needs and devise effective strategies to deliver the appropriate services. Services with must-be and one-dimensional attributes should be given priority, and efforts should be made to provide services with attractive attributes, hence improving the quality of life of breast cancer survivors.

Identification of hub genes and establishment of a diagnostic model in tuberculosis infection.

Tuberculosis (TB) poses significant challenges due to its high transmissibility within populations and intrinsic resistance to treatment, rendering it a formidable respiratory disease with a substantial susceptibility burden. This study was designed to identify new potential therapeutic targets for TB and establish a diagnostic model. mRNA expression data for TB were from GEO database, followed by conducting differential expression analysis. The top 50 genes with differential expression were subjected to GO and KEGG enrichment analyses. To establish a PPI network, the STRING database was utilized, and hub genes were identified utilizing five algorithms (EPC, MCC, MNC, Radiality, and Stress) within the cytoHubba plugin of Cytoscape software. Furthermore, a hub gene co-expression network was constructed using the GeneMANIA database. Consistency clustering was performed on hub genes, and ssGSEA was utilized to analyze the extent of immune infiltration in different subgroups. LASSO analysis was employed to construct a diagnostic model, and ROC curves were used for validation. Through the analysis of GEO data, a total of 159 genes were identified as differentially expressed. Further, GO and KEGG enrichment analyses revealed that these genes were mainly enriched in viral defense, symbiotic defense, and innate immune response-related pathways. Hub genes, including DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15, were identified using cytoHubba analysis of the PPI network. The GeneMANIA analysis unmasked that the co-expression rate of hub genes was 81.55%, and the physical interaction rate was 12.27%. Consistency clustering divided TB patients into two subgroups, and ssGSEA revealed different degrees of immune infiltration in different subgroups. LASSO analysis identified IFIT1, IFIT2, IFIT3, IFIH1, RSAD2, OAS1, OAS2, and STAT1 as eight immune-related key genes, and a diagnostic model was constructed. The ROC curve demonstrated that the model exhibited excellent diagnostic performance. DDX58, IFIT2, IFIH1, RSAD2, IFI44L, OAS2, OAS1, OASL, IFIT1, IFIT3, MX1, STAT1, and ISG15 were hub genes in TB, and the diagnostic model based on eight immune-related key genes exhibited good diagnostic performance.

Aspiration of thrombus for intermediate-risk subacute pulmonary embolism.

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543-603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543-603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.

Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma.

BACKGROUND: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. METHODS: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. RESULTS: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. CONCLUSION: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.

Enhanced response of WO3 thin film through Ag loading towards room temperature hydrogen gas sensor.

This study investigates the enhancement of hydrogen gas-sensing performance by introducing silver (Ag) nanoparticles onto tungsten trioxide (WO3) thin films. Herein, the WO3 thin films are deposited onto SiO2/Si substrates using a sputtering technique and Ag nanoparticles are loaded onto the WO3 surface through a spin coating technique. To evaluate the sensing performance of a hydrogen gas, interdigitated titanium (Ti) electrodes are deposited onto the Ag:WO3 layer. Structural, chemical, and morphological analyses are conducted for both pristine WO3 and Ag:WO3 thin films, followed by the investigation of gas-sensing performance by varying hydrogen gas concentrations from 100 ppm to 300 ppm and operating temperatures between 30 °C and 300 °C. The obtained results demonstrate that Ag:WO3 thin films exhibit a notably enhanced response of 5.08% when exposed to a concentration of 100 ppm of hydrogen gas at room temperature, compared to the pristine WO3 of 3.40%. The fabricated Ag:WO3 sensor exhibits a response time of 3.0 s, a recovery time of 4.5 s, and also demonstrates excellent stability over 45 days period. Finally, with the superior sensitivity and fast response time, the fabricated Ti/Ag:WO3/Ti hydrogen gas sensor test-device can be a potential for improvement of safety from both industrial and environmental perspectives.

Therapy effect of cochleural alternating acoustic beam therapy versus traditional sound therapy for managing chronic idiopathic tinnitus patients.

Idiopathic tinnitus is a common and complex disorder with no established cure. The CAABT (Cochleural Alternating Acoustic Beam Therapy CAABT), is a personalized sound therapy designed to target specific tinnitus frequencies and effectively intervene in tinnitus according to clinical tinnitus assessment. This study aimed to compare the effectiveness of the CAABT and Traditional Sound Therapy (TST) in managing chronic idiopathic tinnitus. This was a randomized, double-blind, parallel-group, single-center prospective study. Sixty adult patients with tinnitus were recruited and randomly assigned to the CAABT or TST group in a 1:1 ratio using a computer-generated randomization. The treatment lasted for 12 weeks, and participants underwent assessments using the tinnitus handicap inventory (THI), visual analog scale (VAS), tinnitus loudness measurements, and resting-state functional magnetic resonance imaging (rs-fMRI). Both groups showed significant reductions in THI scores, VAS scores, and tinnitus loudness after treatment. However, CAABT showed superiority to TST in THI Functional (p = 0.018), THI Emotional (p = 0.015), THI Catastrophic (p = 0.022), THI total score (p = 0.005) as well as VAS score (p = 0.022). More interesting, CAABT showed superiority to TST in the changes of THI scores, and VAS scores from baseline. The rs-fMRI results showed significant changes in the precuneus before and after treatment in both groups. Moreover, the CAABT group showed more changes in brain regions compared to the TST. No side effects were observed. These findings suggest that CAABT may be a promising treatment option for chronic idiopathic tinnitus, providing significant improvements in tinnitus-related symptoms and brain activity.Trial registration: ClinicalTrials.gov:NCT02774122.

Predictive value and potential association of PET/CT radiomics on lymph node metastasis of cervical cancer.

Objective: Due to the information-rich nature of positron emission tomography/computed tomography (PET/CT) images, the authors hope to explore radiomics features that could distinguish metastatic lymph nodes (LNs) from hypermetabolic benign LNs, in addition to conventional indicators. Methods: PET/CT images of 106 patients with early-stage cervical cancer from 2019 to 2021 were retrospectively analyzed. The tumor lesions and LN regions of PET/CT images were outlined with SeeIt, and then radiomics features were extracted. The least absolute shrinkage and selection operator (LASSO) was used to select features. The final selected radiomics features of LNs were used as predictors to construct a machine learning model to predict LN metastasis. Results: The authors determined two morphological coefficient characteristics of cervical lesions (shape - major axis length and shape - mesh volume), one first order characteristics of LNs (first order - 10 percentile) and two gray-level co-occurrence matrix (GLCM) characteristics of LNs (GLCM - id and GLCM - inverse variance) were closely related to LN metastasis. Finally, a neural network was constructed based on the radiomic features of the LNs. The area under the curve of receiver operating characteristic (AUC-ROC) of the model was 0.983 in the training set and 0.860 in the test set. Conclusion: The authors constructed and demonstrated a neural network based on radiomics features of PET/CT to evaluate the risk of single LN metastasis in early-stage cervical cancer.

Investigation of the correlation between the change in the projected lung area and forced vital capacity using biphasic chest dynamic digital radiography: a cross-sectional study.

Background: Chest dynamic digital radiography (DDR) is used as a supplementary tool for the routine pulmonary function test (PFT); however, its potential as a novel standard PFT method has yet to be explored. Therefore, the present study aimed to investigate the correlation between the change in the projected lung area (ΔPLA) and forced vital capacity (FVC) using chest DDR, and to establish a DDR-FVC estimation model and a predictive value model for the ΔPLA. Methods: In total, 139 participants who underwent chest DDR and the PFT in the same period at The First Affiliated Hospital of Guangzhou Medical University from April 2022 to February 2023 were prospectively included in the study. The patients' age, gender, height, and weight measurements were recorded. Additionally, the ΔPLA was measured, and the IWS workstation software was used for automated outlining and calculation. Subsequently, a correlation analysis and regression analysis models were employed to examine the relationship between the ΔPLA, FVC, and individual physiological characteristics. Additionally, an independent sample t-test was used to determine whether there were any significant differences between the normal and abnormal FVC groups. Results: The 139 participants were grouped according to the results of the ratio of measured/predicted FVC values (FVC%pred); those with an FVC%pred ≥80%, were allocated to the normal FVC group, and those with an FVC%pred <80% were allocated to the abnormal FVC group. The correlation coefficient was >0.8 in the full sample; the ΔPLA showed a significant linear correlation with the measured FVC value [r=0.81, 95% confidence interval (CI): 0.75-0.86, P<0.001]. There was a significant difference in the ΔPLA between the normal and abnormal FVC groups. With the ΔPLA, age, gender, height, and weight as predictor variables, the following DDR-FVC estimation model was established: DDR-FVC estimation model = -0.997 + 1.35×10-4 × ΔPLA + 0.017 × height - 0.014 × age + 0.249 × gender (1 for male and 0 for female) [adjusted R2 (adj. R2)=0.731, F=94.615, P<0.001]. The following formula was used to determine the predictive value of the ΔPLA: Predictive value of ΔPLA = -12,504.287 + 173.185 × height + 62.971 × weight - 84.933 × age (adj. R2=0.393, F=20.453, P<0.001). Conclusions: There was a linear correlation between the ΔPLA measured by biphasic chest DDR and the FVC. A model for estimating the FVC was established based on the ΔPLA, which allows the FVC to be assessed by the ΔPLA measured by biphasic chest DDR. A predictive value model for the ΔPLA was also established to provide ΔPLA reference values for assessment and comparison.

Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.

AIMS: To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival. BACKGROUND: Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC. OBJECTIVE: To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model. METHODS: Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features. RESULTS: Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis. CONCLUSION: Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

Evolution and function analysis of auxin response factors reveal the molecular basis of the developed root system of Zygophyllum xanthoxylum.

BACKGROUND: As a xerophytic shrub, forming developed root system dominated with lateral roots is one of the effective strategies for Zygophyllum xanthoxylum to adapt to desert habitat. However, the molecular mechanism of lateral root formation in Z. xanthoxylum is still unclear. Auxin response factors (ARFs) are a master family of transcription factors (TFs) in auxin-mediated biological processes including root growth and development. RESULTS: Here, to determine the relationship between ARFs and root system formation in Z. xanthoxylum, a total of 30 potential ZxARF genes were first identified, and their classifications, evolutionary relationships, duplication events and conserved domains were characterized. 107 ARF protein sequences from alga to higher plant species including Z. xanthoxylum are split into A, B, and C 3 Clades, consisting with previous studies. The comparative analysis of ARFs between xerophytes and mesophytes showed that A-ARFs of xerophytes expanded considerably more than that of mesophytes. Furthermore, in this Clade, ZxARF5b and ZxARF8b have lost the important B3 DNA-binding domain partly and completely, suggesting both two proteins may be more functional in activating transcription by dimerization with AUX/IAA repressors. qRT-PCR results showed that all A-ZxARFs are high expressed in the roots of Z. xanthoxylum, and they were significantly induced by drought stress. Among these A-ZxARFs, the over-expression assay showed that ZxARF7c and ZxARF7d play positive roles in lateral root formation. CONCLUSION: This study provided the first comprehensive overview of ZxARFs and highlighted the importance of A-ZxARFs in the lateral root development.

CXC chemokine receptor 7 ameliorates renal fibrosis by inhibiting ß-catenin signaling and epithelial-to-mesenchymal transition in tubular epithelial cells.

Renal fibrosis is a common feature of various chronic kidney diseases. However, the underlying mechanism remains poorly understood. The CXC chemokine receptor (CXCR) family plays a role in renal fibrosis; however, the detailed mechanisms have not been elucidated. In this study, we investigated the potential role of CXCR7 in mediating renal fibrosis. CXCR7 expression is decreased in unilateral ischemia-reperfusion injury (UIRI) and unilateral ureteral obstruction mouse models. Furthermore, CXCR7 was specifically expressed primarily in the Lotus Tetragonolobus Lectin-expressing segment of tubules, was slightly expressed in the peanut agglutinin-expressing segment, and was barely expressed in the Dolichos biflorus agglutinin-expressing segment. Administration of pFlag-CXCR7, an overexpression plasmid for CXCR7, significantly inhibited the activation of ß-catenin signaling and protected against the progression of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a UIRI mouse model. Using cultured HKC-8 cells, we found that CXCR7 significantly downregulated the expression of active ß-catenin and fibrosis-related markers, including fibronectin, Collagen I, and α-SMA. Furthermore, CXCR7 significantly attenuated TGF-ß1-induced changes in ß-catenin signaling, EMT and fibrosis. These results suggest that CXCR7 plays a crucial role in inhibiting the activation of ß-catenin signaling and the progression of EMT and renal fibrosis. Thus, CXCR7 could be a novel therapeutic target for renal fibrosis.

BREAKING NEW GROUND: STANDARDIZING RAT MODELS FOR CRUSH SYNDROME INVESTIGATIONS.

ABSTRACT: Crush syndrome (CS), alternatively termed traumatic rhabdomyolysis, is a paramount posttraumatic complication. Given the infeasibility of conducting direct simulation research in humans, the role of animal models is pivotal. Regrettably, the dearth of standardized animal models persists. The objective of this study was to construct a repeatable standardized rat CS models and, based on this, simulate specific clinical scenarios. Methods: Using a self-developed multichannel intelligent small-animal crush injury platform, we applied a force of 5 kg to the hind limbs of 8-week-old rats (280-300 g), subjecting them to a continuous 12 h compression to establish the CS model. Continuous monitoring was conducted for both the lower limbs and the overall body status. After decompression, biochemical samples were collected at 3, 6, 12, and 24 h. In addition, we created a CS model after resection of the left kidney (UNx-CS), which was conceptualized to simulate a more challenging clinical scenario to investigate the physiological and pathological responses rats with renal insufficiency combined with crush injury. The results were compared with those of the normal CS model group. Results : Our experiments confirm the stability of the crush injury platform. We defined the standardized conditions for modeling and successfully established rats CS model in bulk. After 12 h of compression, only 40% of the rats in the CS group survived for 24 h. Systemically, there was clear evidence of insufficient perfusion, reflecting the progression of CS from localized to generalized. The injured limbs displayed swelling, localized perfusion deficits, and severe pathological alterations. Significant changes were observed in blood biochemical markers: aspartate transaminase, lactate dehydrogenase, K+, creatine kinase, creatinine, and blood urea nitrogen levels rose rapidly after decompression and were significantly higher than the sham group. The kidney demonstrated characteristic pathological changes consistent with established CS diagnostic criteria. Although the UNx-CS rat model did not exhibit significant biochemical differences and pathological scores when compared with the standard CS model, it did yield intriguing results with regard to kidney morphology. The UNx-CS group manifested a higher incidence of cortical and medullary protein casts compared with the NC-CS group. Conclusion: We developed and iteratively refined a novel digital platform, addressing the multiple uncontrollable variables that plagued prior models. This study validated the stability of the platform, defined the standardized conditions for modeling and successfully established the CS model with good repeatability in bulk. In addition, our innovative approach to model a clinically challenging scenario, the UNx-CS rat model. This offers an opportunity to delve deeper into understanding the combined effects of preexisting renal compromise and traumatic injury. In summary, the development of a standardized, reproducible CS model in rats represents a significant milestone in the study of Crush syndrome. This study is of paramount significance as it advances the standardization of the CS model, laying a solid foundation for subsequent studies in related domains, especially in CS-AKI.

Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease.

AIMS: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences. METHODS: Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero- and first-order absorptions. The elimination phase was evaluated for one- and two-compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method. RESULTS: We constructed a one-compartment linear model with the first parallel absorption model identified as the best-fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non-Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary. CONCLUSIONS: Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.

Preliminary study on the short-term changes of pulmonary perfusion after a single balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Little is known about immediate responses of blood perfusion to the balloon pulmonary angioplasty (BPA) procedure. OBJECTIVES: To investigate the changes in pulmonary perfusion of balloon-dilated vessels and untreated vessels with before, immediately after a single BPA and at follow-up. DESIGN: Retrospective single-center cohort study. METHODS: Patients who had chronic thromboembolic pulmonary hypertension (CTEPH) and completed the pulmonary perfusion single photon emission computed tomography (SPECT) imaging before, immediately after BPA and at follow-up were included. We evaluated the perfusion defects of both-lung, BPA target (balloon dilated) and non-target (untreated) vessel segments according to Begic 3-point scale in each lung segment. RESULTS: Forty patients (40 BPA procedures) were included and were given next BPA after 89 (62-125) days. The hemodynamic parameters including mPAP, PVR, and RAP were significantly improved after a single BPA. Visual scoring results of pulmonary perfusion imaging in 40 BPAs showed the perfusion defect scores of target vessels reduced from 5.6 ± 2.6 to 4.2 ± 2.2 (p < 0.001) immediately after BPA, and then further diminished to 3.1 ± 1.9 (p < 0.001) at follow-up. While in the non-target vessels, the post-BPA perfusion defect scores did not change significantly (13.4 ± 4.7 versus 12.8 ± 4.6, p = 0.182), but tended to decrease at follow-up (12.2 ± 4.2). However, there were 17 BPAs of which the post-BPA perfusion defect scores of non-target vessels increased significantly (p < 0.001), but decreased at follow-up. CONCLUSION: In addition to improving the blood perfusion of target vessels, BPA also has a certain effect on the perfusion of some non-target vessels.