ObjectiveTo establish a highly specific and sensitive triplex TaqMan quantitative PCR method for the detection of mouse hepatitis virus (MHV), mouse parvovirus (MPV), and reovirus type 3 (Reo-3) in laboratory mice. MethodsRecombinant plasmid standards were constructed using conserved genomic regions of the three target viruses. Specific primers and probes were designed, and a triplex TaqMan quantitative PCR (qPCR) system was optimized through preliminary experiments. Sensitivity was evaluated using 10-fold serial dilutions (10¹-10⁷ copies/μL). Intra- and inter-assay repeatability were assessed via reproducibility experiments. ResultsA strong linear correlation (R ²>0.99) was observed between copy number and Ct value at template concentrations of 10²-10⁷ copies/μL. Intra-assay and inter-assay coefficients of variation (CV) were both below 5%. No cross-reactivity was observed with mouse cytomegalovirus (MCMV), vesicular stomatitis virus (VSV), Sendai virus (SeV), or pneumonia virus of mice (PVM). ConclusionThe triplex TaqMan quantitative PCR method established in this study has high sensitivity, good repeatability, and strong specificity. It enables the rapid, specific, and sensitive detection of MHV, MPV, and Reo-3, allows the simultaneous detection of multiple pathogens in a single tube, and can be applied to the detection of clinical samples from laboratory animals and to epidemiological investigations, thereby providing effective scientific and technological support for the prevention and control of viral infection and the interruption of transmission.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

In the context of global warming, protecting outdoor workers from occupational heat exposure has become an important public health concern. This review summarized the principle, applicability, and limitation of three categories of wet bulb globe temperature (WBGT) prediction models: empirical regression models, heat-balance models, and machine-learning models. Drawing on international experience from the United States, Europe, and Japan, this review further examined the technical challenges of applying WBGT-based prediction models to large-scale occupational heat stress early warning systems. In response to gaps in occupational heat stress management in China, WBGT should be considered a core assessment indicator to support a transition from passive response to proactive intervention. A localized implementation pathway is proposed, incorporating mechanism-based model calibration, regional parameter adaptation, and multi-source data fusion. Strengthening collaboration between public health and meteorological departments and developing platform-based flexible intervention strategies for workers in new forms of employment may improve the targeting of occupational heat stress early warning and health protection. Future research should focus on physics-constrained machine learning, refined microenvironmental prediction, and individualized risk assessment to support the development of a digitally enabled occupational heat-health protection framework.

BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Objective To explore the relationship between levels of vascular endothelial growth factor(VEGF),insulin-like growth factor 1(IGF-1),and transforming growth factor-β1(TGF-β1)in the synovial fluid of children with avascular necrosis of the femoral head(also known as Perthes disease)and the efficacy of postoperative revascularization,aiming to provide a basis for subsequent diagnosis and treatment.Methods A retrospective study was conducted on 262 children with Perthes disease admitted to the Affiliated Hospital of Gansu University of Chinese Medicine from January 2023 to June 2024.Based on postoperative revascularization efficacy,patients were divided into good revascularization group(n=228)and poor revascularization group(n=34).For poor revascularization group,a 1:2 matched case-control design was used to select 68 age-matched children with hip synovitis who underwent hip joint fluid puncture as control group.Additionally,82 children with Perthes disease treated at the hospital from June 2024 to January 2025 were enrolled as a validation cohort for nomogram model verification.The expression levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of three groups were compared.Confounding biases were controlled through univariate and stratified analyses.Binary logistic regression analysis was used to identify independent factors affecting the revascularization effect.R software was utilized to draw and verify the nomogram model for predicting the postoperative revascularization effect.Results The levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children in poor revascularization group were all higher than those in control group and good revascularization group(P<0.05).After three types of reconstructive surgeries,the levels of VEGF,IGF-1 and TGF-β1 in the synovial fluid of children with poor revascularization were all higher than those in children with good revascularization(P<0.05);however,there was no statistically significant difference in the above indicators among different surgical types(P>0.05).Binary logistic regression analysis showed that the levels of VEGF,IGF-1,and TGF-β1 in the synovial fluid were independent risk factors for poor postoperative revascularization in children with Perthes disease.The area under the ROC curve of the nomogram model established accordingly for predicting poor postoperative revascularization in children with Perthes disease was 0.875(95%CI 0.805-0.945),with a sensitivity of 0.874 and a specificity of 0.851.Moreover,the calibration curve and decision curve analysis(DCA)indicated that the model had good clinical applicability.Conclusions The increased levels of VEGF,IGF-1 and TGF-β1 in synovial fluid are associated with poor postoperative revascularization in children with Perthes disease.These three factors are expected to become prognostic indicators for children with Perthes disease.

Objective To investigate the effect and mechanism of dexmedetomidine(Dex)in alleviating sevoflurane(Sev)-induced cognitive dysfunction in neonatal rats via the Janus kinase 2/signal transducer and activators of transcription 3(JAK2/STAT3)signaling pathway.Methods A total of 50 neonatal Sprague-Dawley(SD)rats were randomly divided into control group,model group,Dex group,AG490 group,and Colivelin group,with 10 rats in each group.Except for control group,the rats in the other four groups were used to construct a model of cognitive dysfunction in neonatal rats by inhaling Sev.Before modeling,Dex group was intraperitoneally injected with 20 μg/kg Dex;AG490 group was intraperitoneally injected with 20 μg/kg Dex and 1 mg/kg AG490;Colivelin group was intraperitoneally injected with 20 μg/kg Dex,1 mg/kg AG490,and 1 mg/kg Colivelin;control group and model group were intraperitoneally injected with an equal doses of physiological saline.The novel object recognition test and step-down test were used to detect the cognitive,learning,and memory functions of neonatal rats.TUNEL method was used to detect the cell apoptosis rate in the hippocampus.Rhodamine 123 staining was used to detect the mitochondrial membrane potential in the hippocampus.ELISA method was used to detect the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in the hippocampus.DHE probe method was used to detect the intracellular reactive oxygen species(ROS)content.qRT-PCR was used to detect the mRNA expression levels of phosphorylated JAK2(p-JAK2),phosphorylated STAT3(p-STAT3),Synapsin-I,brain-derived neurotrophic factor(BDNF),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax).Western Blotting was used to detect the protein expression levels of p-JAK2,p-STAT3,JAK2,and STAT3 in the hippocampus.Results Compared with control group,model group showed cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with model group,Dex,AG490,and Colivelin groups showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,increased mRNA expression levels of p-JAK2,p-STAT3,Synapsin-I,BDNF,and Bcl-2,decreased Bax mRNA level,increased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with Dex group,AG490 and Colivelin groups exhibited cognitive and memory impairment,significantly increased apoptosis rate,increased levels of ROS and MDA,decreased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and decreased mitochondrial membrane potential in the hippocampus(P<0.05).Compared with AG490 group,Colivelin group showed significantly improved cognitive and memory impairment,significantly decreased apoptosis rate,decreased levels of ROS and MDA,increased SOD level,decreased mRNA expression levels of p-JAK2 and p-STAT3,Synapsin-I,BDNF,and Bcl-2,increased Bax mRNA expression level,decreased ratios of p-JAK2/JAK2 and p-STAT3/STAT3,and increased mitochondrial membrane potential in the hippocampus,with statistically significant differences(P<0.05).Conclusion Dex can inhibit the oxidative stress in the hippocampus of brain tissue in Sev-induced neonatal rats and improve their cognitive,learning,and memory impairment,which may be related to the activation of JAK2/STAT3 signaling pathway.