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.

ObjectiveTo explore the establishment of a rat model of diabetic macrovascular atherosclerosis （DMA） with Qi and Yin deficiency syndrome induced by high-fat diet， streptozotocin （STZ）， and Yin-depleting herbs， and to evaluate its biological characteristics. MethodsForty SD rats were randomly divided into a blank group （n=10） and a modeling group （n=30）. Except for the blank group， rats in the model group were fed a high-fat diet for 4 weeks， followed by intraperitoneal injection of STZ （30 mg·kg^-1） to establish a diabetic model. Twenty-four successfully modeled diabetic rats were randomly divided into a model group （n=7）， a Qi and Yin deficiency syndrome group （n=8）， and a counter-syndrome group （n=9）. Except for the model group， rats received intragastric administration of Yin-depleting herbs （1.2 g·kg^-1） for 8 weeks. The counter-syndrome group was further treated with Shenqi compound formula （1.69 g·kg^-1） for an additional 8 weeks. General condition and body weight were recorded， and syndrome-related indicators were assessed， including precordial temperature， skin moisture content， grip strength， open-field test performance， and tongue appearance. Serum levels of vascular endothelial growth factor （VEGF）， endothelin-1 （ET-1）， vascular cell adhesion molecule-1 （VCAM-1）， insulin-like growth factor-1 （IGF-1）， and monocyte chemotactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay （ELISA）. Fasting blood glucose， blood lipids， hemorheological parameters， and coagulation function were analyzed using an automatic biochemical analyzer. Vascular ultrasound and hematoxylin-eosin （HE） staining were used to evaluate vascular lesions. ResultsIn terms of syndrome manifestations， compared with the blank group， body weight increased rapidly during the first 5 weeks in the model， Qi and Yin deficiency， and counter-syndrome groups. After STZ injection combined with Yin-depleting herbal administration at week 5， body weight decreased significantly （P<0.01） and continued to decline until the end of the experiment. Rats exhibited decreased activity， irritability， coarse and yellowish fur with obvious shedding， polydipsia， polyphagia， frequent urination， and dry stools， which were most pronounced in the Qi and Yin deficiency group. Grip strength decreased， peak activity time occurred earlier， total distance in the open-field test was reduced， and residence time was prolonged. Precordial temperature decreased （P<0.01）， while paw temperature increased （P<0.05）， and skin moisture and oil content were reduced （P<0.05， P<0.01）. In terms of disease-related indicators， compared with the blank group， fasting blood glucose was significantly increased （>16.7 mmol·L^-1） in the model and Qi and Yin deficiency groups， and blood lipid levels were significantly elevated （P<0.05）. Vascular-related factors ET-1， MCP-1， VCAM-1， and VEGF were significantly increased （P<0.05，P<0.01）， while IGF-1 was significantly decreased （P<0.01）. Pathological examination of the aortic valve showed valvular thickening and structural disorganization. Carotid artery examination revealed discontinuity of the intima， foam cell accumulation beneath the intima， disordered smooth muscle arrangement， and widened intercellular spaces. Compared with the model group， ET-1， MCP-1， and VEGF levels were significantly decreased in both the Qi and Yin deficiency group and the counter-syndrome group. The reductions in ET-1 and MCP-1 were more pronounced in the Qi and Yin deficiency group （P<0.01）， while the decrease in VCAM-1 was more significant in the counter-syndrome group （P<0.05）. Compared with the blank group， the Qi and Yin deficiency group showed significantly prolonged activated partial thromboplastin time （APTT）， thrombin time （TT）， and prothrombin time （PT） （P<0.01）. The erythrocyte deformability index （TK）， erythrocyte sedimentation rate， erythrocyte electrophoresis index， and whole blood low-shear viscosity all showed increasing trends. Vascular ultrasound revealed reduced arterial blood flow velocity， increased vascular resistance， and intimal thickening without plaque formation. The aortic intima showed no obvious overall thickening， with only occasional localized thickening and foam cell presence， and carotid artery injury was observed. ConclusionA rat model of DMA with Qi and Yin deficiency syndrome was successfully established using high-fat diet feeding combined with STZ injection and Yin-depleting herbal administration. Shenqi compound formula effectively alleviated Qi and Yin deficiency syndrome， regulated glucose and lipid metabolism， improved hemorheological and coagulation function， reduced vascular lesion severity， and demonstrated potential for early prevention and treatment of DMA.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

Background Swimming is becoming increasingly popular for its combined leisure and fitness benefits. However, polluted swimming pool water may pose various health risks. Previous studies have indicated that health indicators of swimming venues have lower qualification rates compared to other public places, highlighting the urgent need to optimize hygiene management measures. Objective To assess the overall hygiene status and identify the key factors influencing water quality in Shanghai’s swimming venues from 2010 to 2024, and to provide a scientific basis for optimizing water quality management. Methods Water quality was assessed in three stages (2010—2019, 2020—2022, and 2023—2024) based on the monitoring data of Shanghai’s swimming venues (2010—2024). The influences of monitoring stage, region, season, scale, day of week, and per capita attendance on water quality were analyzed using chi-square tests and logistic regression. Results From 2010 to 2024, water quality was monitored in 1478 swimming venues. The compliance rates of turbidity, pH, urea, oxidation-reduction potential, free residual chlorine, combined residual chlorine, total bacteria, coliforms, and heat-resistant coliforms in swimming pool water, and free residual chlorine in the foot disinfection basin water samples were 99.56%, 94.73%, 73.00%, 47.50%, 56.55%, 54.12%, 97.74%, 99.49%, 99.90%, and 69.19%, respectively. The overall water quality compliance rate was 85.28%. The main non-compliant indicators for swimming pool water were urea, ORP, free residual chlorine, and combined residual chlorine, along with free chlorine residual in the foot disinfection basin water samples. Using the period before the implementation of the new national standard as reference, the results of logistic regression revealed that the qualification rates of urea, ORP, and free residual chlorine in the swimming pool water samples, as well as free residual chlorine in foot disinfection basin water samples, were significantly higher during the two phases after launching the new standard (2020–2022 and 2023–2024), and the associated odds ratios (95%CI) were 1.28 (1.00, 1.64) and 1.48 (1.12, 1.95), 13.35 (7.63, 23.37) and 10.78 (7.00, 16.60), 2.54 (1.81, 3.58) and 3.18 (2.41, 4.20), and 3.14 (2.14, 4.60) and 2.83 (1.89, 4.23), respectively. Compared with the reference group, those sampled in urban pools and in non-summer seasons showed higher qualification rates of urea and ORP; in contrast, the pools with high visitor flow showed lower qualification rates of free residual chlorine in both water samples of swimming pools and foot disinfection basins (P<0.05). Conclusion The implementation of the new national standard has effectively enhanced the management standards and significantly improved overall water quality of swimming venues in Shanghai. However, the compliance rates of free residual chlorine and urea in swimming pool water still need further improvement. The compliance of some indicators is influenced by region, season, scale, and average passenger flow, particularly in small suburban swimming venues. Future efforts should focus on refining water quality management strategies and enhancing public health management.

Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*