Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Purpose To investigate the clinicopathological features of traditional serrated adenoma(TSA).Methods A retrospective analysis was conducted on the clinical data,endoscopic,and pathological features of 200 TSA patients.HE staining and immunohistochemical staining were performed.The clinical pathological features were statistically analyzed using x2 test,and relevant literature was reviewed.Results There were 114 males(57.0％)and 86 females(43.0％),with ages ranging from 27 to 92 years(mean age 56.2 years).Among the patients,147(73.5％)were aged ≥ 50 years,and 53(26.5％)were aged＜50 years.Of the 207 TSA lesions,143(69.1％)were located in the distal colon and rectum,while 57(27.5％)were in the proximal colon and rectum.Endoscopic features included 72 lesions(34.8％)with a perpendiculated appearance,48 lesions(23.2％)with a flat appear-ance,and some exhibiting a pinecone-like appearance.The maximum diameter of the lesions was ≤ 10 mm in 136 ca-ses(65.7％),and＞10 mm in 71 cases(34.3％).The typical histopathological features of TSA included serrated contours,eosinophilic cytoplasm,pencil-like nuclei,and ectopic crypt foci.The most common pathological type was the classic TSA(152 lesions,73.4％),followed by the mucin-rich TSA(39 lesions,18.8％).12 cases(5.8％)of TSA exhibited high-grade intraepithelial neoplasia(HGIN)and 3 case(1.5％)of TSA progressed to carcinoma,con-sistent with TSA-originated colorectal cancer(TSA-CRC).Immunophenotype:in 34 cases TSA,Ki67 showed diffuse positivity in basal cells and scattered positivity on the surface.In all 35 cases TSA,p53 showed weak positive nuclear positivity(1％to 60％),and PTEN and MLH1 were retained.In the 12 cases of TSA with HGIN and 3 cases of TSA-CRC,Ki67 showed diffusely positive,CK20 was strongly positive diffusely,and MLH1 was retained.In 9 cases of TSA with HGIN,p53 was diffusely strongly positive,and in 12 cases,PTEN was lost.All 3 cases of TSA-CRC showed dif-fuse strong nuclear p53 positivity.The molecular detection showed there were BRAF V600E gene mutation in 8 cases.There were 6 cases with KRAS G12V mutation as well as 1 case with KRAS G13D mutation among the 7 cases of KRAS mutation.The primary surgical approach(111 cases,53.6％)was endoscopic mucosal resection(EMR).Conclu-sion TSA exhibits characteristic histological and endoscopic features.Lesions with a maximum diameter＞10 mum are more likely to progress to HGIN or adenocarcinoma.It is crucial to enhance the awareness of pathologists and clini-cians,particularly regarding TSA with atypical hyperplasia or invasive carcinoma,to avoid misdiagnosis and missed di-agnoses.

Objective To investigate the impacts of long non coding RNA(LncRNA)-PH domain containing 5 antisense RNA 1(FGD5-AS1)on the proliferation,migration,and invasion of colorectal cancer(CRC)cells by regulating the miR-299-5p/recombinant lysine specific demethylase 4B(KDM4B)axis.Methods The expressions of LncRNA FGD5-AS1,miR-299-5p,and KDM4B were detected by qRT-PCR in the surgically resected CRC tissues and adjacent tissues of 34 CRC patients CRC cells HCT116 were separated into si-NC group,si-FGD5-AS1 group,si-FGD5-AS1+inhibitor NC group,and si-FGD5-AS1+miR-299-5p inhibitor group.The levels of mRNA in each group were detected.CCK8,scratch assay,and Transwell assay were ap[plied to detect the proliferation,migration,and invasion of HCT116 cells in each group.Western blot was applied to detect the expression of proteins.Dual luciferase reporter gene assay verified the interaction mechanism between LncRNA FGD5-AS1 and miR-299-5p,and between miR-299-5p and KDM4B.Results LncRNA FGD5-AS1 and KDM4B were highly expressed in CRC tissue,while miR-299-5p was low expressed in CRC tissue(P＜0.05).The expression of LncRNA FGD5-AS1 mRNA,KDM4B mRNA,OD450,scratch healing rate,invasion number,PCNA,MMP-2,MMP-9,KDM4B in the si-FGD5-AS1 group were lower than those in the si-NC group,the expression of miR-299-5p mRNA was higher than that in the si-NC group(P＜0.05).Compared with the si-FGD5-AS1 group and si-FGD5-AS1+inhibitor NC group,the expression of miR-299-5p in the si-FGD5-AS1+miR-299-5p inhibitor group decreased(P＜0.05),the KDM4B mRNA,OD450,scratch healing rate,number of invasions,and expression of PCNA,MMP-2,MMP-9,KDM4B increased(P＜0.05).LncRNA FGD5-AS1 targeted negative regulation of miR-299-5p,while miR-299-5p targeted negative regulation of KDM4B.Conclusion Knocking down LncRNA FGD5-AS1 may inhibit the proliferation,migration,and invasion of CRC cells,and its mechanism may be achieved by regulating the miR-299-5p/KDM4B signaling axis.

Objective To explore the value of dual-energy CT Bone Marrow Edema in quantitatively evaluating the timing of rib fracture evolution.Methods Sixty patients with thoracic trauma were scanned by dual-energy CT.Using CT Bone Marrow Edema technique,bone marrow CT values were standardized and quantified in both the Bone Marrow Edema area at the rib fracture site and in normal areas 1 cm on both sides of the fracture.The increments of standardized CT values for Bone Marrow Edema and VNCa were obtained for three stages of healing.The numerical variables were statistically described,and both the standardized CT value increments and VNCa standardized CT value increments were compared between the three stages and between each pair of stages.Diagnostic efficacy for stages with significant differences was evaluated using the area under the receiver operating characteristic(ROC)curve(AUC),and Cut-offvalues were calculated.Results There were significant differences in standardized CT value increments and VNCa standardized CT value increments across the three stages of Bone Marrow Edema(H=10.788,p=0.005;F=115.787,p=0.000).The standardized CT value increment of Bone Marrow Edema showed significant differences between the cartilaginous callus stage(fibrous callus stage)and the bony callus-remodeling stage(H=54.958,p=0.003),while the other pairwise comparisons showed no statistical significance(H=-25.603,p=0.183;H=29.354,p=0.113,respectively).However,the VNCa standardized CT value increments showed statistical significance across all three pairwise comparisons(all p=0.000).The ROC curve for differentiating the cartilaginous callus stage(fibrous callus stage)from the bony callus-remodeling stage using Bone Marrow Edema standardized CT value increment had an AUC of 0.652,with a Cut-offvalue of 81.575 Hu.The ROC curve for distinguishing the hematoma inflammation stage from the cartilaginous callus stage(fibrous callus stage)using VNCa standardized CT value increment had an AUC of 0.668,with a Cut-offvalue of 55.700 Hu.The ROC curve for differentiating the cartilaginous callus stage(fibrous callus stage)from the bony callus-remodeling stage using VNCa standardized CT value increment had an AUC of 0.905,with a Cut-offvalue of 37.625 Hu.Conclusion Dual-energy CT Bone Marrow Edema can quantitatively evaluate the timing of rib fracture evolution,and the differences in standardized CT value increments at different stages can provide a theoretical basis for forensic identification of fractures at different time periods.The Cut-offvalues of standardized CT value increments can,to some extent,predict the time stage of a fracture,providing quantitative evidence for forensic experts in the identification of rib fractures.

Objective::This study aimed to investigate the feasibility, efficacy, and safety of using a miniature mobile integrated cabin-theatre equipped with angiography and surgical operating room capabilities, and to explore its therapeutic scope, effectiveness, and operational mode.Methods::A miniature mobile integrated operating cabin-theatre was deployed across 15 hospitals in 15 cities or counties in China from April 2012 to November 2024. The interventions and outcomes of interventional and minimally invasive surgical procedures were prospectively observed and evaluated; perioperative complications were documented, and the stability, adaptability, and mobility of the integrated system were assessed.Results::A total of 133 procedures were successfully performed, 130 of which were interventional and 3 minimally invasive. The angiography machine showed good imaging performance without any equipment failures, loosening, or damage, with normal chamber unfolding. One patient experienced a fever the day after laparoscopy, while none of the other patients exhibited perioperative complications such as infection, surgical site bleeding/hematoma, or reperfusion arrhythmia. The instrument was easily manipulated, aligning with the needs of clinical intervention and surgery, and was perceived by patients as being a comfortable environment, with no psychological or other obvious discomfort.Conclusions::The miniature mobile integrated cabin-theatre, comprising an angiography machine and an operating room, allows interventional or minimally invasive surgical procedures to be performed smoothly and safely. It can also provide rapid and efficient on-site treatment of acute and critical illnesses across multiple body systems, including the cardiovascular, cerebrovascular, and gastrointestinal systems.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients. METHODS: This secondary analysis of data from a randomized controlled trial involved 1,720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments. RESULTS: Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872. CONCLUSION We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; Machine Learning ; Postoperative Complications/etiology* ; Risk Factors ; Randomized Controlled Trials as Topic ; Secondary Data Analysis