Retinopathy of prematurity(ROP)is a leading cause of childhood blindness, with extremely preterm and very-low-birth-weight infants now constituting the main high-risk group. ROP progresses in two stages: early retinal microvascular degeneration and progressive vascular arrest, followed by abnormal neovascularization in the avascular area. Early oxidative and nitrosative stress—amplified by oxygen fluctuations and immature antioxidant defenses—drives the two-phase pathogenesis via hypoxia-inducible factor/vascular endothelial growth factor(HIF/VEGF), NOX/STAT3, and nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE)pathways, mediating apoptosis of endothelial cells, damage to barrier and pathological angiogenesis. This review systematically analyzes different oxygen-induced retinopathy(OIR)models, elucidates key signaling pathways including Notch, Wnt in physiological and pathological vascularization, with particular emphasis on the biphasic effects of Nrf2 and the differential roles of NOX signaling between phases. We also discuss the limitations of anti-VEGF therapy and oxygen management principles. Reactive oxygen species(ROS)play context-dependent roles across vaso-obliteration and neovascularization phases. Based on mechanistic insights, we propose future directions including combined/sequential interventions, ferroptosis and lipid peroxidation targeting, nano-delivery systems for enhanced bioavailability, and perinatal safety assessment strategies, aiming to provide translatable mechanistic basis for reducing pathological neovascularization while promoting physiological vascular development.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

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.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

In the field of substance detection,ion dissociation techniques have become crucial for enhancing qualitative accuracy.By applying external energy to induce dissociation of ions in the substance being analyzed,the internal structural information can be obtained,thereby improving qualitative capabilities.Current research on ion dissociation techniques primarily focuses on tandem mass spectrometry,which typically requires a vacuum environment.However,research on ambient ion dissociation techniques is less developed,with some progress made in the field of tandem ion mobility spectrometry.Recently,the development of field-induced dissociation(FID)in this area has enabled ambient dissociation of various explosive and volatile alcohol ions.Nevertheless,the limitation imposed by the maximum breakdown field of air restricts the energy of the electric field,making it challenging to dissociate ions with high energy requirements,such as those of drugs.To address this issue,in this work,an ambient heat-induced dissociation(HID)technique based on high temperatures was proposed,in which an ambient ion heat-induced dissociation unit was developed and integrated into a home-made ion trap mass spectrometer.Experiments were conducted on four representative drug samples,e.g.methamphetamine,heroin,cocaine,and ketamine.The parent ions mass spectra,low vacuum collision-induced dissociation(CID)mass spectra and ambient HID mass spectra for each sample were obtained.By analyzing and comparing the fragmentation products from ambient and low vacuum dissociation,the feasibility of the ambient HID technique was verified.This technique provided a method for ion dissociation in single mass analyzers without tandem mass spectrometry capability and offered a new research direction for the future development of tandem ion mobility spectrometry.

Microfluidic chips have revolutionized analytical sciences through miniaturization and high-throughput capabilities.However,conventional static devices are constrained by fixed architectures,functional rigidity,and high customization costs.In recent years,,the emerging configurable and reconfigurable microfluidic technologies have provided solutions for these limitations through dynamic adaptability.Configurable systems enable post-fabrication customization via modular assembly or boundary modification,offering cost-effective functional versatility.Reconfigurable microfluidics represents a more advanced paradigm,incorporating real-time decision-making and dynamic control through physical/virtual boundary adjustments during operation.These adaptive systems enable precise manipulation of microenvironments for applications ranging from single-cell manipulation to dynamic biochemical synthesis.In this review,a ″static-dynamic boundary″ framework to systematically analyze both technologies was proposed,and the design rationales,operational mechanisms,and implementation strategies were compared.The development history of these two techniques was introduced,and the applications demonstrated their transformative potential in developing intelligent lab-on-chip systems,while technical challenges in standardization and control interfaces were critically assessed.The development trend on integrating smart materials and AI-driven automation to advance next-generation adaptive microfluidic platforms was prospected.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.