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Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

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ETHNOPHARMACOLOGICAL RELEVANCE: Increasing evidence suggests that ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation, may play a substantial role in the traumatic brain injury (TBI) pathophysiology. 3-n-butylphthalide (NBP), a compound extracted from the seeds of Apium graveolens Linn (Chinese celery) and used in China to treat ischemic stroke, has demonstrated encouraging anti-reactive oxygen species (ROS) effects. Ascertaining whether NBP can inhibit ferroptosis and its mechanism could potentially expand its use in models of neurological injury and neurodegenerative diseases. METHODS AND RESULTS: In this study, we used erastin-induced in vitro ferroptosis models (HT22 cells, hippocampal slices, and primary neurons) and an in vivo controlled cortical impact mouse model. Our study revealed that NBP administration mitigated erastin-induced death in HT-22 cells and decreased ROS levels, lipid peroxidation, and mitochondrial superoxide indicators, resulting in mitochondrial protection. Moreover, the ability of NBP to inhibit ferroptosis was confirmed in organotypic hippocampal slice cultures and a TBI mouse model. NBP rescued neurons, inhibited microglial activation, and reduced iron levels in the brain tissue. The protective effect of NBP can be partly attributed to the inhibition of the AHR-CYP1B1 axis, as evidenced by RNA-seq and CYP1B1 overexpression/inhibition experiments in HT22 cells and primary neurons. CONCLUSIONS: Our study underscores that NBP inhibition of the AHR-CYP1B1 axis reduces ferroptosis in neuronal damage and ameliorates brain injury.

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BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

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Background: Diabetic foot ulcer (DFU) is a serious clinical problem with high amputation and mortality rates, yet there is a lack of desirable therapy. While the extracellular matrix (ECM) contributes significantly to wound healing, ECM-related biomarker for DFU is still unknown. The study was designed to identify ECM-related biomarker in DFU using bioinformatics and machine learning and validate it in STZ-induced mice models. Methods: GSE80178 and GSE134431 microarray datasets were fetched from the GEO database, and differentially expressed genes (DEGs) analysis was performed, respectively. By analyzing DEGs and ECM genes, we identified ECM-related DEGs, and functional enrichment analysis was conducted. Subsequently, three machine learning algorithms (LASSO, RF and SVM-RFE) were applied to filter ECM-related DEGs to identify key ECM-related biomarkers. Next, we conducted immune infiltration analysis, GSEA, and correlation analysis to explore the hub gene underlying mechanism. A lncRNA-miRNA-mRNA and drug regulatory network were constructed. Finally, we validated the key ECM-related biomarker in STZ-induced mice models. Results: One hundred and forty-five common DEGs in adult DFU between the two datasets were identified. Taking the intersection of 145 common DEGs and 964 ECM genes, we identified 13 ECM-related DEGs. Thirteen ECM-related DEGs were mainly enriched in pathways associated with tissue remodeling, inflammation and defense against infectious agents. Ultimately, CTSH was identified as the key ECM-related biomarker. CTSH was associated with difference immune cells during the occurrence and development of DFU, and it influenced hedgehog, IL-17 and TNF signaling pathway. Additionally, CTSH expression is correlated with many ECM- and immune-related genes. A lncRNA-miRNA-mRNA and drug regulatory network were constructed with 10 lncRNAs, 2 miRNAs, CTSH and 1 drug. Finally, CTSH was validated as a key biomarker for DFU in animal models. Conclusion: Our study found that CTSH can be used for both diagnostic and prognostic purposes and might be a potential therapeutic target.

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This research explores a novel paradigm for preserving topological segmentations in existing error-bounded lossy compressors. Today's lossy compressors rarely consider preserving topologies such as Morse-Smale complexes, and the discrepancies in topology between original and decompressed datasets could potentially result in erroneous interpretations or even incorrect scientific conclusions. In this paper, we focus on preserving Morse-Smale segmentations in 2D/3D piecewise linear scalar fields, targeting the precise reconstruction of minimum/maximum labels induced by the integral line of each vertex. The key is to derive a series of edits during compression time. These edits are applied to the decompressed data, leading to an accurate reconstruction of segmentations while keeping the error within the prescribed error bound. To this end, we develop a workflow to fix extrema and integral lines alternatively until convergence within finite iterations. We accelerate each workflow component with shared-memory/GPU parallelism to make the performance practical for coupling with compressors. We demonstrate use cases with fluid dynamics, ocean, and cosmology application datasets with a significant acceleration with an NVIDIA A100 GPU.

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BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.

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OBJECTIVES: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients. METHODS: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set. RESULTS: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702). CONCLUSION: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction.

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INTRODUCTION: Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support. METHOD AND ANALYSIS: This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted 'normal' range, which is predefined as oesophageal pressure-time product per minute between 50 and 200 cmH2O⋅s/min, for each patient during 48 hours of pressure support adjustment. ETHICS AND DISSEMINATION: The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05963737; ClinicalTrials.org.

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BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

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Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage heart failure. As a complex pathologic condition, it involves intricate regulatory processes at the cellular and molecular levels. The immune system and cardiovascular system are closely interconnected, with immune cells playing a crucial role in maintaining cardiac health and influencing disease progression. Consequently, alterations in the cardiac microenvironment are influenced and controlled by various immune cells, such as macrophages, neutrophils, dendritic cells, eosinophils, and T-lymphocytes, along with the cytokines they produce. Furthermore, studies have revealed that Gata6+ pericardial cavity macrophages play a key role in regulating immune cell migration and subsequent myocardial tissue repair post IHD onset. This review outlines the role of immune cells in orchestrating inflammatory responses and facilitating myocardial repair following IHD, considering both macro and micro views. It also discusses innovative immune cell-based therapeutic strategies, offering new insights for further research on the pathophysiology of ischemic heart disease and immune cell-targeted therapy for IHD.

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Despite advances in treatment, myocardial infarction remains the leading cause of heart failure and death worldwide, and the restoration of coronary blood flow can also cause heart damage. In this study, we found that corosolic acid (CA), also known as plant insulin, significantly protects the heart from ischemia-reperfusion (I/R) injury. In addition, CA can inhibit oxidative stress and improve mitochondrial structure and function in cardiomyocytes. Subsequently, our study demonstrated that CA improved the expression of the mitophagy-related proteins Prohibitin 2 (PHB2), PTEN-induced putative kinase protein-1 (PINK1), and Parkin. Meanwhile, through molecular docking, we found an excellent binding between CA and PHB2 protein. Finally, the knockdown of PHB2 eliminated the protective effect of CA on hypoxia-reoxygenation in cardiomyocytes. Taken together, our study reveals that CA increases mitophagy in cardiomyocytes via the PHB2/PINK1/Parkin signaling pathway, inhibits oxidative stress response, and maintains mitochondrial function, thereby improving cardiac function after I/R.

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BACKGROUND: Acute lung injury (ALI) is a respiratory disease characterized by pulmonary inflammation and increased microvascular permeability, resulting in significant mortality and a lack of effective pharmacological treatment. Huangqin Qingfei Decoction (HQQFD), a Traditional Chinese Medicine (TCM) prescription known for its heat-clearing and detoxifying properties, has shown efficacy in treating ALI. However, the underlying mechanisms of HQQFD to against ALI remain to be elucidated. PURPOSE: This study aims to discover the mechanisms and the principal bioactive compounds contributing to HQQFD's protective effects in the treatment of ALI. METHODS: An ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS) method was employed to characterize the chemical profile in HQQFD and xenobiotics (prototypes and metabolites) in rat lung tissue. Based on prototypes identified, a symptom-guided pharmacological networks of ALI were performed. Molecular docking and extensive literature reviews were conducted to validate our findings. RESULTS: A total of 105 compounds were identified in HQQFD, and a total of 194 HQQFD-related xenobiotics (30 prototypes and 163 metabolites) were detected in rat lung tissue. Based on prototypes identified in rat lung, a symptom-guided pharmacological networks of ALI were constructed, AKT1, TNF, EGFR, MMP2, GSK3B, STAT3, MAPK8, IL-6, CDK2 and TP53 were finally identified as key targets. Subsequently, 11 compounds with protective and therapeutic activity were selected by molecular docking analysis, including genipin 1-gentiobioside, chrysin-6-C-α-L-arabinoside-8-C-ß-d-glucoside, scutellarin, chrysin-6-C-ß-d-glucoside-8-C-α-L-arabinoside, 6''-O-[(E)-p-coumaroyl] genipin-gentiobioside, apigenin 7-O-glucoside, baicalin, dihydrobaicalin, wogonoside, crocin I, crocetin. Bioinformatics and literature analysis suggested that, baicalin, wogonoside, genipin 1-gentiobioside and crocetin may be the primary active compounds of HQQFD, potentially targeting GSK3B, MAPK8, IL-6, AKT1 and TNF for HQQFD in addressing ALI. The therapeutic effects of HQQFD may be mediated through the IL-17 and PI3K-AKT signaling pathways. CONCLUSION: The predominant components of HQQFD against ALI are baicalein, wogonoside, genipin 1-gentiobiosid and crocetin, with the IL-17 and PI3K-AKT pathways playing crucial roles. This study provides a foundational guide for future research and introduces innovative methods for exploring the mechanisms of other drug combinations or TCM formulas.

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BACKGROUND: To evaluate the clinical efficacy of sublingual-specific immunotherapy (SLIT) and pulmonary function in children with allergic rhinitis and asthma before and after puberty. METHODS: This retrospective analysis included 136 patients aged 4-18 years with allergic asthma and rhinitis who received two years of SLIT treatment. Patients were divided into two groups based on age: the prepubertal group (4-10 years old) and the pubertal group (11-18 years old). After half a year, one year, and two years of SLIT, the total nasal symptom score (TNSS), total rhinitis medication score (TRMS), daytime asthma symptom score (DASS), nighttime asthma symptom score (NASS), total asthma medication score (TAMS), asthma control test (ACT), and peak expiratory flow rate (PEF%) were evaluated and compared with the baseline before treatment. RESULTS: In both groups, TNSS, TRMS, DASS, NASS, TAMS, ACT, and PEF% improved significantly after half a year, one year, and two years of SLIT treatment. After half a year of treatment, prepubertal patients showed better therapy for TNSS, DASS, NASS, and TAMS compared to the pubertal group. The TAMS of the pubertal group was higher than that of the prepubertal group after one year of treatment. Finally, the PEF% showed better therapy compared to the pubertal group. CONCLUSION: SLIT treatment with Dermatophagoides farinae drops can effectively control the symptoms of rhinitis and asthma in children with allergic rhinitis and asthma before and after puberty, reduce the use of symptomatic drugs, significantly improve the pulmonary function of patients, and have better effects on asthma in prepubertal children than in adolescents.

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Urban flood risk assessment is a complex task, as it requires extensive knowledge about hydrological features of the catchment, hydraulic characteristics of the drainage network and social characteristics of residential areas. How to accurately and efficiently quantify regional risk has always been a challenge in this field. To solve the problem, this study is developed to propose a novel integrated urban flood risk assessment approach based on one-two dimensional coupled hydrodynamic model and improved projection pursuit method. Two open source software like urban storm flood management model (SWMM) and TELEMAC-2D are introduced to build the one-two coupling hydrodynamic model through proprietary programming, which can accurately simulate urban inundation process. Based on the simulation results of hydrodynamic model and literature review, a set of urban flood risk assessment index system containing physical mechanism and statistical mechanism related index is established, including a total of 12 indicators covering three dimensions like hazard factor, exposure factor and vulnerability factor. Then an Improved Projection Pursuit (IPP) method coupling k-means clustering algorithm is proposed to determine the index weight. The novel integrated urban flood risk assessment approach is implemented in Suyu district, China. The results demonstrate that the accuracy and efficiency of evaluation urban flood risk assessment are greatly improved by the integrated approach. In conclusion, this research offers a novel methodology for urban flood risk assessment and contributes to decision-making in environmental management.

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OBJECTIVES: To compare the diagnostic performance of three readers using BI-RADS and Kaiser score (KS) based on mass and non-mass enhancement (NME) lesions. METHODS: A total of 630 lesions, 393 malignant and 237 benign, 458 mass and 172 NME, were analyzed. Three radiologists with 3 years, 6 years, and 13 years of experience made diagnoses. 596 cases had diffusion-weighted imaging, and the apparent diffusion coefficient (ADC) was measured. For lesions with ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 as the modified KS +, and the benefit was assessed. RESULTS: When using BI-RADS, AUC was 0.878, 0.915, and 0.941 for mass, and 0.771, 0.838, 0.902 for NME for Reader-1, 2, and 3, respectively, better for mass than for NME. The diagnostic accuracy of KS was improved compared to BI-RADS for less experienced readers. For Reader-1, AUC was increased from 0.878 to 0.916 for mass (p = 0.005) and from 0.771 to 0.822 for NME (p = 0.124). Based on the cut-off value of BI-RADS ≥ 4B and KS ≥ 5 as malignant, the sensitivity of KS by Readers-1 and -2 was significantly higher for both Mass and NME. When ADC was considered to change to modified KS +, the AUC and the accuracy for all three readers were improved, showing higher specificity with slightly degraded sensitivity. CONCLUSION: The benefit of KS compared to BI-RADS was most noticeable for the less experienced readers in improving sensitivity. Compared to KS, KS + can improve specificity for all three readers. For NME, the KS and KS + criteria need to be further improved. CLINICAL RELEVANCE STATEMENT: KS provides an intuitive method for diagnosing lesions on breast MRI. BI-RADS and KS face greater difficulties in evaluating NME compared to mass lesions. Adding ADC to the KS can improve specificity with slightly degraded sensitivity. KEY POINTS: KS provides an intuitive method for interpreting breast lesions on MRI, most helpful for novice readers. KS, compared to BI-RADS, improved sensitivity in both mass and NME groups for less experienced readers. NME lesions were considered during the development of the KS flowchart, but may need to be better defined.

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Introduction: This study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020). Methods and Results: In total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates. Discussion: These findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

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BACKGROUND: Turbo spin-echo (TSE) diffusion-weighted imaging (DWI) sequences may reduce susceptibility artifacts and image distortion in sellar region, allowing better visualization of small pituitary lesions, and may be used to assist in the diagnosis of pituitary microadenomas. PURPOSE: To explore the application value of conventional MRI combined with DWI sequences in the diagnosis of microprolactinomas. STUDY TYPE: Prospective. POPULATION: Thirty-four patients in microprolactinomas with high signal on T2WI (HT2-PRL) group (34 females, 34 ± 7 years), 26 patients in microprolactinomas with equal or low signal on T2WI (ELT2-PRL) group (21 females, 34 ± 7 years), 35 patients with hyperprolactinemia (33 females, 32 ± 8 years), and 30 normal controls (25 females, 31 ± 7 years). FIELD STRENGTH/SEQUENCE: TSE sequence at 3 T. ASSESSMENT: Pituitary morphological parameters (such as length and volume), dynamic contrast-enhanced parameters (such as time to peak) and the apparent diffusion coefficients (ADCs) were measured in each group. STATISTICAL TESTS: ANOVA and Mann-Whitney U test were used to compare parameters among groups. Spearman's coefficient was used to evaluate the correlation between variables. ROC analysis was used to assess the performance of the parameters. A P-value <0.05 was considered statistically significant. RESULTS: The pituitary volume of patients in HT2-PRL, ELT2-PRL, and hyperprolactinemia group were 831.00 (747.60, 887.60), 923.63 ± 219.34, and 737.20 (606.40, 836.80) mm3. The pituitary maximum height in these three groups were 7.03 (6.43, 8.63), 8.03 ± 1.41, and 6.63 ± 1.28 mm, respectively. The lesion ADC value was significantly correlated with T2 relative signal intensity (the ratio of signal intensity of microprolactinoma or anterior pituitary to left temporal cortex) (r = 0.821). Compared with patients with hyperprolactinemia, the diagnostic efficacy of T2 relative signal intensity was higher in HT2-PRL group, with an AUC of 0.954, whereas the ADC value was the highest in ELT2-PRL group, with an AUC of 0.924. CONCLUSION: DWI sequences can be used to assist in the diagnosis of pituitary microadenomas. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

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The possible contamination routes, environmental adaptation, and genetic basis of Cronobacter spp. in infant and follow-up formula production factories and retailed products in mainland China have been determined by laboratory studies and whole-genome comparative analysis in a 7-year nationwide continuous surveillance spanning from 2012 to 2018. The 2-year continuous multicenter surveillance of the production process (conducted in 2013 and 2014) revealed that the source of Cronobacter spp. in the dry-blending process was the raw dry ingredients and manufacturing environment (particularly in the vibro sieve and vacuum cleaner), while in the combined process, the main contamination source was identified as the packing room. It is important to note that, according to the contamination control knowledge obtained from the production process surveillance, the contamination rate of retail powdered infant formula (PIF) and follow-up formula (FUF) products in China decreased significantly from 2016 onward, after improving the hygiene management practices in factories. The prevalence of Cronobacter spp. in retailed PIF and FUF in China in 2018 was dramatically reduced from 1.55 % (61/3925, in 2012) to an average as low as 0.17 % (13/7655 in 2018). Phenotype determination and genomic analysis were performed on a total of 90 Cronobacter spp. isolates obtained from the surveillance. Of the 90 isolates, only two showed resistance to either cefazolin or cefoxitin. The multilocus sequence typing results revealed that C. sakazakii sequence type 1 (ST1), ST37, and C. malonaticus ST7 were the dominant sequence types (STs) collected from the production factories, while C. sakazakii ST1, ST4, ST64, and ST8 were the main STs detected in the retailed PIF and FUF nationwide. One C. sakazakii ST4 isolate (1.1 %, 1/90) had strong biofilm-forming ability and 13 isolates (14.4 %, 13/90) had weak biofilm-forming ability. Genomic analysis revealed that Cronobacter spp. have a relatively stable core-genome and an increasing pan-genome size. Plasmid IncFIB (pCTU3) was prevalent in this genus and some contained 14 antibacterial biocide- and metal-resistance genes (BMRGs) including copper, silver, and arsenic resistant genes. Plasmid IncN_1 was predicted to contain 6 ARGs. This is the first time that a multi-drug resistance IncN_1 type plasmid has been reported in Cronobacter spp. Genomic variations with respect to BMRGs, virulence genes, antimicrobial resistance genes (ARGs), and genes involved in biofilm formation were observed among strains of this genus. There were apparent differences in copies of bcsG and flgJ between the biofilm-forming group and non-biofilm-forming group, indicating that these two genes play key roles in biofilm formation. The findings of this study have improved our understanding of the contamination characteristics and genetic basis of Cronobacter spp. in PIF and FUF and their production environment in China and provide important guidance to reduce contamination with this pathogen during the production of PIF and FUF.

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