Ezhou Central Hospital

Copper transporters (COPTs) and chaperones (CCs) regulate root Cu+ transport and homeostasis. Basic helix-loop-helix107 (bHLH107)-mediated ACC synthesis 8 (ACS8) activation is crucial for Cu+-triggered immunity (CuTI) in Arabidopsis leaves. Here, we aimed to identify the components of COPTs and CCs and elucidate their roles in CuTI. Six copt mutants were screened for Cu+-mediated resistance to Pst DC3000 and ACS8 activation. Protein interactions were evaluated using split luciferase complementation, membrane-based yeast two-hybrid, and pull-down assays. Cu+-triggered defense responses were analyzed with comparative RNA-seq profiling and reverse transcription quantitative polymerase chain reaction. Among copt1 to copt6, only copt4 attenuated Cu+-mediated immune responses, while COPT4 abolished the transport of Cu+ alone. Intriguingly, COPT4 interacts with the complete transporter proteins COPT1 and COPT3. Similar to copt4 and bhlh107 copt4 plants, copt1 copt3 plants exhibited impaired Cu+-mediated bacterial load reduction and ACS8 induction. Compared with the wild-type, it also attenuated Cu+-mediated differentially expressed genes and copper accumulation, as did the copt4 plants. Furthermore, we revealed that the CCs of Arabidopsis homolog of anti-oxidant 1 (ATX1)interact with COPT1 or COPT3 but not with COPT4, which is involved in CuTI. Collectively, our findings suggest that COPT4 manipulates two redundant heterodimers to interact with ATX1, subsequently activating the Cu+-responsive module of bHLH107-ACS8 inside plant cells.

Aging is accompanied by chronic low-grade inflammation (inflammaging), driving age-related diseases. Urolithin A (UA), a gut microbial metabolite, possesses anti-inflammatory properties, yet its mechanism in hepatic aging remains unclear. This study investigated UA's effects on aging-associated inflammation and the involvement of Nur77 in D-galactose-induced macrophage senescence and mouse liver aging models using molecular docking, Western blotting, and immunoprecipitation. UA alleviated cellular senescence markers (p53, p21), suppressed pro-inflammatory factors (IL-6, IL-1β), and elevated anti-inflammatory IL-10. Mechanistically, UA enhanced Nur77 protein stability by inhibiting MDM2-mediated ubiquitination and degradation, thereby restoring inflammatory homeostasis. In vivo, UA ameliorated D-gal-induced liver injury and modulated the hepatic Nur77-MDM2 axis. Conclusion: UA stabilizes Nur77 by inhibiting its ubiquitination, alleviating hepatic aging-associated inflammation. This study identifies the MDM2-Nur77 axis as a potential therapeutic target for hepatic aging.

Abstract Introduction Postmenopausal osteoporosis, defined by reduced bone mineral density and fracture risk, is a major health concern. Bisphosphonates are standard therapy, but the added value of exercise is uncertain. This study examined their combined effects on BMD, bone turnover, body composition, strength, and balance in postmenopausal women. Content PubMed, Embase, and Cochrane Central were systematically searched for RCTs on bisphosphonates, exercise, or their combination in postmenopausal osteoporosis. Primary outcomes were changes in BMD at lumbar spine, femoral neck, and total hip. Secondary outcomes included bone turnover markers (ALP-B, NTx), body composition (fat and lean mass), and leg extensor strength. Study quality was assessed with Cochrane Risk of Bias tool. Mean differences with 95 % confidence intervals (CI) were calculated using a random-effects model, with heterogeneity evaluated by I 2 . Summary Six RCTs with 1,059 subjects qualified for inclusion. Bisphosphonate + exercise treatment showed small and non-significant improvement in lumbar spine and femoral neck BMD (p=0.41 and p=0.11, respectively), and no significant change in total hip BMD (p=0.48). Levels of ALP-B significantly increased (p=0.0008), reflecting bone turnover rather than a direct clinical benefit; NTx showed non-significant trend (p=0.10). Fat mass significantly decreased (p<0.00001), leg strength significantly increased (p<0.00001), and lean mass showed no significant change (p=0.14). Outlook Combined exercise and bisphosphonates yield modest yet consistent improvements in site-specific BMD, fat loss, and strength in postmenopausal osteoporosis, supporting exercise as an adjunct to pharmacologic therapy for musculoskeletal health.

Myocardial ischemia-reperfusion injury (MIRI) is a secondary injury that occurs upon the restoration of blood flow to ischemic myocardium, significantly diminishing the clinical benefits of reperfusion therapy. Excessive production of reactive oxygen species (ROS) and subsequent oxidative stress are recognized as central pathological mechanisms underlying MIRI. In recent years, significant progress has been made in the development of therapeutic agents targeting ROS scavenging and the modulation of oxidative stress. This review systematically summarizes recent advancements in MIRI interventions based on antioxidant mechanisms, including strategies for direct ROS elimination and the activation of endogenous antioxidant pathways. Through integrated target prediction and network analysis, the molecular basis and interactions of various antioxidant strategies are elucidated, highlighting compounds such as Honokiol as critical nodes within the intervention network. Additionally, utilizing the National Center for Biotechnology Information (NCBI) database, this work compiles and discusses the clinical progress of related antioxidant drugs in myocardial protection, offering a comprehensive overview and future perspectives. Ultimately, this review provides valuable insights for the future development of effective and low-toxicity anti-MIRI pharmaceutical agents. Keywords: Myocardial ischemia-reperfusion injury; ROS; Oxidative stress; Antioxidants

Toll-like receptor signaling molecules are involved in tumor associated inflammatory response. This study aims to investigate the role of Toll-like receptor signaling molecule gene polymorphisms in the risk of HPV-related cervical lesions. A total of 352 study subjects, 178 women with cervical lesions and 174 women without cervical lesion were involved in a case-control study. Real-time polymerase chain reaction (real-time PCR) was used to detect HR-HPV genotypes. Genotyping of SNPs for MYD88 gene (rs7744) and TRAF3 gene (rs1131877, rs12435483, rs3803286, rs12147254) were performed by Sanger sequencing. The MYD88 and TRAF3 haplotype frequencies were analyzed using the HaploView 4.2 program. Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR). The TRAF3 rs3803286 (A) variant allele (OR = 0.724, p = 0.045) and TRAF3 rs1131877 (TC) variant genotype (OR = 0.563, p = 0.023) were found to be associated with a significantly reduced risk of cervical lesions. rs3803286-HPV-16/18 was the best interaction model for the risk of cervical lesions (p = 0.0004). TRAF3 rs3803286 and rs1131877 are potential biomarkers of susceptibility to cervical lesions. Not applicable.

The coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan. This article evaluated clinical characteristics, and imaging manifestations in Ezhou, an early locked-down city, 80 kilometers east of Wuhan. We analyzed data from 98 confirmed severe COVID-19 patients in Ezhou Central Hospital between February 1st and March 22nd, 2020. We compared patients’ laboratory results, imaging manifestations, and treatments between survival and death groups. Of these 98 confirmed COVID-19 patients, 24 individuals (24.6%) had chronic diseases. The main symptoms of critically ill patients were fever (86.7%), cough (83.7%), and dyspnea (59.1%). Common complications were acute respiratory distress syndrome (ARDS; 49%), acute kidney injury (37.7%), and multiple organ dysfunction syndrome (MODS; 32.6%). Computed tomography (CT) scans displayed ground-glass opacity at subpleural regions that were associated with interlobular septal thickening. Within 28 days, 39 (39.8%) patients died. Compared to survivors, the death group had a higher median age (69.8 vs. 61.3, p < 0.05), and were more prone to ARDS (100% vs. 15.2%) and MODS (76% vs. 3.4%). Our report showed that in the early days of the COVID-19 outbreak, there was a high mortality rate in critically ill patients. Elderly patients (>65 years) normally have an increased risk of complications and ARDS. Most non-survivors were highly dependent upon mechanical ventilation. CT scans with imaging manifestations showed abnormal conditions in the lower multiple bilateral lung lobes, which provides a useful characterization of this fatal disease by recognizing COVID-19 pneumonia and assessing its evolution for the target for intervention of the patient recovery.

To systematically reveal the spatiotemporal distribution, collaboration networks, and thematic evolution of global transrectal ultrasound (TRUS) research in prostate cancer from 2015 to 2024 using bibliometric analysis and visualization. A total of 12,894 relevant articles from the Web of Science database were analyzed using VOSviewer and CiteSpace for co-occurrence networks, burst detection, and density visualization, combined with social network analysis (SNA) and kernel density estimation (KDE) to decode country/institution collaboration patterns and geographical agglomeration. Annual publications peaked at 1800 in 2019, with a secondary surge in 2023 (1563 articles) driven by AI applications (e.g., AI-assisted biopsy). Mean citations per article reached 7.8 in 2020, coinciding with the release ofGLOBOCAN 2020and the rise of teleultrasound research. The United States (5333 articles) and Canada formed the North American core cluster (edge weight 5333 × 1099), while the UK (1287 articles) and Germany served as secondary hubs in Europe. Asian countries showed scattered distributions, though South Korea (2015-2017 burst strength 7.64, elastography) and Australia (2019-2022 burst strength 8.33, focal ablation) emerged as regional technical frontiers. The University of Toronto (242 articles) led TRUS-targeted biopsy research, while the University of Michigan became a rising affiliation due to TRUS-AI integration (post-2020 annual publications > 50). The high-impact journalJ Clin Oncol(5783 citations) focused on fusion biopsy, with annual articles increasing from 42 to 117.Keywords shifted from "systematic biopsy" (2015-2017) and "radiotherapy planning" (2018-2020) to "AI-assisted diagnosis" (2021-2024 burst strength 20.6) and "teleultrasound" (COVID-19-related studies, annual growth 19%), reflecting technology-driven clinical transformation. TRUS research exhibits significant regional inequality and technological iteration, with AI integration and multimodal fusion (e.g., MRI-TRUS fusion) as future priorities. Strengthening cross-regional collaboration is recommended to promote technological equity, particularly for low-cost TRUS innovations in resource-constrained regions.

[Objective] To explore the correlations between the levels of serum monocyte chemoattractant protein-4 (MCP-4), heart-type fatty acid binding protein (FABP3), and chemokine ligand 9 (CXCL9) and myocardial damage in severe Mycoplasma pneumoniae (SMPP) patients. [Methods] A total of 158 patients with severe Mycoplasma pneumoniae complicated with myocardial damage were included in the SMPP group. They were divided into a myocardial damage group (n=42) and a nonmyocardial damage group (n=116) according to whether myocardial damage occurred. The control group consisted of an additional 102 healthy people who were examined throughout the same time period. The levels of serum MCP-4, FABP3 and CXCL9 in the two groups were compared. The general clinical data of the patients were recorded. Multivariate logistic analysis was conducted to analyze the risk factors for myocardial damage in patients with severe mycoplasma complicated with pneumonia. [Results] The levels of serum MCP-4, FABP3 and CXCL9 in the SMPP group were significantly greater (all P&lt;0.05). Compared with those in the nonmyocardial damage group, Serum MCP-4, FABP3, and CXCL9 levels were considerably higher (all P&lt;0.05) in the group with myocardial injury. Age, sex, diabetes, smoking history, hypoxemia, jaundice, and chronic obstructive pulmonary disease (COPD) did not differ statistically significantly between the two groups (all P&gt;0.05). Compared with those in the nonmyocardial damage group, the proportions of patients with hypertension, coronary heart disease and anemia, as well as the levels of serum MCP-4, FABP3 and CXCL9, in the myocardial damage group were significantly greater (all P&lt;0.05). Combined hypertension, coronary heart disease, anemia, and high levels of serum MCP-4, FABP3, and CXCL9 are risk factors for myocardial damage in patients with severe mycoplasma infection. The levels of serum MCP-4, FABP3 and CXCL9 in patients were positively correlated with the incidence of myocardial damage in patients with severe mycoplasma infection (all P&lt;0.05). [Conclusion] The levels of serum MCP-4, FABP3 and CXCL9 are positively correlated with myocardial damage in patients with severe Mycoplasma pneumoniae. Moreover, combined hypertension, coronary heart disease, anemia and high levels of serum MCP-4, FABP3 and CXCL9 are risk factors for myocardial damage in patients with severe mycoplasma infection. These three factors can be used as biological indicators of myocardial damage in patients with severe mycoplasma infection in clinical practice and are highly important for the assessment of patients' conditions and the formulation of treatment plans.

N-acetylcysteine (NAC) is a derivative of cysteine with potent mucolytic and antioxidant properties. However, the pharmacokinetics of NAC tablets remain unclear in healthy Chinese subjects. This study aimed to assess the pharmacokinetics, bioequivalence, and safety of a domestically manufactured NAC tablet (600mg) compared with the reference formulation in healthy Chinese volunteers under both fasting and fed conditions. A single-dose, randomized, open-label, two-formulation, crossover bioequivalence study was conducted, using a two-period, two-sequence design under fasting conditions and a four-period, fully replicated crossover design under fed conditions. Blood samples were collected at predetermined time points and analyzed using a validated liquid chromatography-tandem mass spectrometry method. The 90% confidence intervals for the geometric mean ratios (test/reference) of the maximum plasma concentration, the area under the concentration-time curve from time zero to the last measurable concentration, and from time zero to infinity were all within the accepted bioequivalence range of 80%-125%. Furthermore, both the test and reference formulations were well tolerated, and no serious adverse events were reported. These results demonstrate that the test and reference NAC tablets are bioequivalent and exhibit similar pharmacokinetic profiles and safety in healthy Chinese subjects under both fasting and fed conditions.