Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury: PERK as a potential target for intervention.

JOURNAL/nrgr/04.03/01300535-202505000-00028/figure1/v/2024-07-28T173839Z/r/image-tiff Several studies have shown that activation of unfolded protein response and endoplasmic reticulum (ER) stress plays a crucial role in severe cerebral ischemia/reperfusion injury. Autophagy occurs within hours after cerebral ischemia, but the relationship between ER stress and autophagy remains unclear. In this study, we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury. We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 subunit alpha (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP), increased neuronal apoptosis, and induced autophagy. Furthermore, inhibition of ER stress using inhibitors or by siRNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis, indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy. Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis, indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury. Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy, and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

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.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure: A multicenter study.

BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder.

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is classified under fibrotic interstitial pneumonia, characterized by a chronic and progressive course. The predominant clinical features of IPF include dyspnea and pulmonary dysfunction. AIM: To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients. METHODS: A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023. These patients were divided into two groups: control group (n = 53) and observation group (n = 60). In the control group, patients received routine therapy in combination with methylprednisolone tablets, while those in the observation group received routine therapy together with pirfenidone. After applying these distinct treatment approaches to the two groups, we assessed several parameters, including the overall effectiveness of clinical therapy, the occurrence of adverse reactions (e.g., nausea, vomiting, and anorexia), symptom severity scores, pulmonary function index levels, inflammatory marker levels, and the 6-min walk distance before and after treatment in both groups. RESULTS: The observation group exhibited significantly higher rates than the control group after therapy, with a clear distinction (P < 0.05). After treatment, the observation group experienced significantly fewer adverse reactions than the control group, with a noticeable difference (P < 0.05). When analyzing the symptom severity scores between the two groups of patients after treatment, the observation group had significantly lower scores than the control group, with a distinct difference (P < 0.05). When comparing the pulmonary function index levels between the two groups of patients after therapy, the observation group displayed significantly higher levels than the control group, with a noticeable difference (P < 0.05). Evaluating the inflammatory marker data (C-reactive protein, interleukin-2 [IL-2], and IL-8) between the two groups of patients after therapy, the observation group exhibited significantly lower levels than the control group, with significant disparities (P < 0.05). Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group, with a marked difference (P < 0.05). CONCLUSION: Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function, elevate inflammatory factor levels, and increase the distance covered in the 6-min walk test. This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Surgical management of adult hand macrodactyly in a 49-year-old patient: A case report.

BACKGROUND: Macrodactyly is a rare congenital malformation characterized by an increase in the size of all structures of a digit, accounting for less than 1% of all congenital upper extremity conditions. CASE SUMMARY: We report a case involving a 49-year-old woman who presented for the first time with untreated, radial-sided hand macrodactyly. We performed soft tissue debulking, amputation, median nerve neurotomy and coaptation, and carpal tunnel release. At the 6-year follow-up, no significant growth was observed in the bone or soft tissue of the affected area. CONCLUSION: Tissue overgrowth in patients with progressive macrodactyly can continue and progress excessively with age. Median nerve neurotomy and coaptation play a crucial role in preventing recurrence of the deformity.

Potential Roles of Long Non-coding RNAs in the Pathogenesis of Periodontitis: Inflammation Response, Immune Infiltration, Collagen Fibers Synthesis, and Bone Remodeling.

BACKGROUND: It is evident that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of periodontitis. However, the detailed functional mechanisms remain unknown. OBJECTIVE: This study aimed to elucidate the pathogenic mechanisms of lncRNAs in periodontitis by investigating their regulation of protein-coding gene expression. METHOD: Human Gingival Fibroblasts-1 (HGF-1) were stimulated with 5 µg/mL of Lipopolysaccharide (LPS) for 24 hours to construct the periodontitis cell model. qRTPCR and western blot analyses were carried out to determine mRNA and protein levels of genes induced by LPS or involved in the inflammatory response. Cytokine levels and inflammatory proteins were assayed using ELISA. Transcriptome sequencing and analysis were conducted to reveal the expression signatures of lncRNAs. DESeq2 (v1.4.5) was used to analyze differentially expressed genes. Gene function enrichment was carried out using Phyper. AnimalTFDB v3.0 was used to analyze transcription factors involved in the pathogenesis of periodontitis. Prot\ein domains and families of the target proteins were identified based on the Pfam protein family database. RESULTS: In LPS-treated HGF-1 cells, we detected the secretion of TNF-α and IL-1ß, along with the production of MDA and ROS, indicating that LPS significantly triggered inflammatory responses and oxidative stress in HGF-1 cells. A total of 15,295 lncRNAs were detected in both the control (ConT) and LPS-treated groups. We selected 10 significantly differentially co-expressed lncRNA-coding genes (MIR222HG, SNHG15, SNHG12, URS00005F6AA3, URS00009C153E, URS0000D57D7F, URS00019A4688, URS00019AF240, URS00019C6526, and URS0001A00B79) as potential biomarkers for diagnosing the progression of periodontitis. An interaction network consisting of 2 lncRNA- encoding genes (MIR222HG and SNHG15) and protein-encoding genes (CBX5, NUPR1, CHAC1, and MAB21L3) may be involved in the pathogenesis of periodontitis. The ceRNA network analysis revealed the differentially expressed lncRNAs to be involved in inflammatory response, immune infiltration, collagen fiber synthesis, and bone remodeling in LPS-induced periodontitis. CONCLUSION: This study has identified pivotal molecules implicated in the pathogenesis of periodontitis, including those involved in inflammation regulation, collagen fiber synthesis, and bone remodeling. Our findings may contribute to explaining how lncRNAs participate in the pathological process of periodontitis.

HTFSMMA: Higher-Order Topological Guided Small Molecule-MicroRNA Associations Prediction.

Small molecules (SMs) play a pivotal role in regulating microRNAs (miRNAs). Existing prediction methods for associations between SM-miRNA have overlooked crucial aspects: the incorporation of local topological features between nodes, which represent either SMs or miRNAs, and the effective fusion of node features with topological features. This study introduces a novel approach, termed high-order topological features for SM-miRNA association prediction (HTFSMMA), which specifically addresses these limitations. Initially, an association graph is formed by integrating SM-miRNA association data, SM similarity, and miRNA similarity. Subsequently, we focus on the local information of links and propose target neighborhood graph convolutional network for extracting local topological features. Then, HTFSMMA employs graph attention networks to amalgamate these local features, thereby establishing a platform for the acquisition of high-order features through random walks. Finally, the extracted features are integrated into the multilayer perceptron to derive the association prediction scores. To demonstrate the performance of HTFSMMA, we conducted comprehensive evaluations including five-fold cross-validation, leave-one-out cross-validation (LOOCV), SM-fixed local LOOCV, and miRNA-fixed local LOOCV. The area under receiver operating characteristic curve values were 0.9958 ± 0.0024 (0.8722 ± 0.0021), 0.9986 (0.9504), 0.9974 (0.9111), and 0.9977 (0.9074), respectively. Our findings demonstrate the superior performance of HTFSMMA over existing approaches. In addition, three case studies and the DeLong test have confirmed the effectiveness of the proposed method. These results collectively underscore the significance of HTFSMMA in facilitating the inference of associations between SMs and miRNAs.

Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis.

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

[Clinical characteristics of children with anti-neutrophil cytoplasmic antibody-associated vasculitis]. / å„¿ç«¥æŠ—ä¸­æ€§ç²’ç»†èƒžèƒžè´¨æŠ—ä½“ç›¸å ³æ€§è¡€ç®¡ç‚Žä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.

[Correlation of anti-C1q antibodies with active systemic lupus erythematosus and lupus nephritis in children]. / 抗C1qæŠ—ä½“ä¸Žå„¿ç«¥æ´»åŠ¨æ€§ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®å’Œæ´»åŠ¨æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Perception of Medication Safety-Related Behaviors Among Different Age Groups: Web-Based Cross-Sectional Study.

BACKGROUND: Previous research and safety advocacy groups have proposed various behaviors for older adults to actively engage in medication safety. However, little is known about how older adults perceive the importance and reasonableness of these behaviors in ambulatory settings. OBJECTIVE: This study aimed to assess older adults' perceptions of the importance and reasonableness of 8 medication safety behaviors in ambulatory settings and compare their responses with those of younger adults. METHODS: We conducted a survey of 1222 adults in the United States using crowdsourcing to evaluate patient behaviors that may enhance medication safety in community settings. A total of 8 safety behaviors were identified based on the literature, such as bringing medications to office visits, confirming medications at home, managing medication refills, using patient portals, organizing medications, checking medications, getting help, and knowing medications. Respondents were asked about their perception of the importance and reasonableness of these behaviors on a 5-point Likert rating scale in the context of collaboration with primary care providers. We assessed the relative ranking of behaviors in terms of importance and reasonableness and examined the association between these dimensions across age groups using statistical tests. RESULTS: Of 1222 adult participants, 125 (10.2%) were aged 65 years or older. Most participants were White, college-educated, and had chronic conditions. Older adults rated all 8 behaviors significantly higher in both importance and reasonableness than did younger adults (P<.001 for combined behaviors). Confirming medications ranked highest in importance (mean score=3.78) for both age groups while knowing medications ranked highest in reasonableness (mean score=3.68). Using patient portals was ranked lowest in importance (mean score=3.53) and reasonableness (mean score=3.49). There was a significant correlation between the perceived importance and reasonableness of the identified behaviors, with coefficients ranging from 0.436 to 0.543 (all P<.001). CONCLUSIONS: Older adults perceived the identified safety behaviors as more important and reasonable than younger adults. However, both age groups considered a behavior highly recommended by professionals as the least important and reasonable. Patient engagement strategies, common and specific to age groups, should be considered to improve medication safety in ambulatory settings.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

Plasmid-mediated azithromycin resistance in non-typhoidal Salmonella recovered from human infections.

OBJECTIVES: Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. METHODS: A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. RESULTS: The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. CONCLUSIONS: These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.

Impact of different concentration iodinated contrast media on pain and comfort in abdominal computed tomography.

OBJECTIVES: To investigate whether high concentration iodinated contrast media (CM), compared with low concentration CM, could reduce pain and discomfort levels in patients who had level II and III venous conditions. METHODS: This prospective, single-center study enrolled patients who had level II and III venous conditions and underwent abdominal contrast-enhanced CT scan between July 2021 and February 2022. The venous condition to establish peripheral venous access for CM injection was graded using the Intravenous Access Scoring system, of which level II and III indicated poor venous condition and difficult venous access. Patients received iomeprol 400 in high concentration group and ioversol 320 in low group at an identical iodine delivery rate of 1.12 gI/s. The primary outcomes were pain and comfort levels. The secondary outcomes included adverse events and image quality. Patients rated pain intensity via Numerical Rating Scale and comfort level via Visual Analogue Scale with higher scores indicating higher levels of pain and discomfort. Quantitative and qualitative image assessment were compared between two groups. Continuous variables were compared using Student's t test or Mann-Whitney U test. Categorical variables were compared using χ2 test, χ2 test for trend or Fisher's exact test. RESULTS: A total of 206 patients (mean age, 60.13 ± 12.14 years; 81 males) were included with 99 in the high concentration group and 107 in the low concentration group. The high group had significantly lower pain scores (median 1 [IQR: 0-2] vs 2 (IQR 2-4), p < 0.001) and comfort scores (1 [IQR: 0-3] vs 3 [IQR: 2-5], p < 0.001) than the low group. Incidence of CM extravasation did not significantly differ (1.0 % vs 4.5 %, p = 0.214). No hypersensitivity reaction was observed. Qualitative assessment showed higher clarity scores of intrahepatic hepatic artery and portal vein in the high group. Quantitative assessment results were comparable between two groups. CONCLUSION: High concentration iodinated CM could lower pain intensity and improve comfort levels without comprising image quality of CT scan. High concentration CM is a preferable choice in patients with poor venous conditions during contrast-enhanced CT scan.

The effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration.

The saline wastewater produced in industrial activities and seawater use would flow into wastewater treatment plants and affect the characteristic of extracellular polymeric substance (EPS) of activated sludge, which could potentially impact the removal of antibiotics via adsorption. Nonetheless, the effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration and the underlying mechanism remain largely unknown. In this study, the effect of salinity on the adsorption removal of a typical antibiotic, i.e., trimethoprim (TMP) at trace concentration (25.0 µg/L) was evaluated. The results showed the content of EPS was decreased significantly from 56.36 to 21.70 mg/g VSS when the salinity was increased from 0 to 10 g/L. Protein fractions occupied the predominant component of EPS, whose concentration was decreased from 38.17 to 12.83 mg/g VSS. The equilibrium adsorption capacity of activated sludge for TMP was decreased by 49.70% (from 4.97 to 2.50 µg/g VSS). The fluorescence quenching results indicated the fluorescence intensity of tryptophan-like substances was decreased by 30% and the adsorption sites of EPS were decreased from 0.51 to 0.21 when the salinity was increased. The infrared spectrum and XPS results showed that the nitrogen-containing groups from protein were decreased significantly. The circular dichroic analysis showed α helix structure of protein in EPS was decreased with the increase of salinity, which was responsible for the decrease of adsorption capacity for TMP.