OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

Climate change is altering the Earth's water cycle system. The resulting three extreme weather events—heatwaves, droughts, and extreme precipitation—impacts urban and rural water security through multi-layered mechanisms. A primary structural disparity exists between urban and rural systems: while urban areas benefit from comprehensive and standardized pipe networks that ensure terminal water quality, rural areas often suffer from "last mile" vulnerability due to inadequate infrastructure and outdated purification facilities. Extreme weather can directly alter the microbial community structure, concentrations of chemical pollutants and physicochemical properties of source water. These alterations interfere with the efficiency of water treatment processes and ultimately compromise the integrity of distribution systems. Because distribution networks often lack real-time monitoring and adaptive response capabilities, they have emerged as the most vulnerable link in the "water source-water treatment-distribution system" chain. Based on a systematic analysis of these chain-wide impacts, this paper proposed a series of control strategies, including security frameworks based on multi-model coupling and water source protection measures, improvement of water treatment technologies, optimization of distribution systems, and development of new water quality monitoring methods. These strategies aim to enhance the climate adaptability of urban and rural drinking water systems through multi-dimensional intervention, providing a theoretical basis for constructing climate-resilient water infrastructure.

Objective To assess the echogenicity of the ultrasound-guided catheter and its associated delivery system. Methods The study consisted of in vitro characterization experiments and animal studies. In the in vitro phase, the acoustic and mechanical properties of the ultrasound-guided catheter were compared with those of the traditional MPA2 catheter, including parameters such as echo intensity, recognizability, and angle dependence. In the animal experiments, a ventricular septal defect (VSD) model was established in miniature pigs to compare the procedural performance of the ultrasound-guided delivery system versus the conventional system. Evaluation indicators included the time required for the system to cross the VSD, the detection rate of the system within the right ventricle, and the occurrence of intraoperative complications. Results The ultrasound-guided catheter demonstrated a significantly higher mean echo intensity than the MPA2 catheter [(237.3±1.8) dB vs. (190.9±13.1) dB, P<0.001] and a markedly improved recognizability rate (82.3%±5.6% vs. 26.7%±3.2%, P<0.001), along with better angle independence and image quality. In animal experiments, the ultrasound-guided delivery system significantly reduced the time required to cross the VSD [(18.5±5.7) min vs. (30.3±4.5) min, P<0.001] and substantially increased the detection rate within the right ventricle (100.0% vs. 30.0%). No severe complications occurred in any experimental animal. Conclusion The ultrasound-guided catheter and its corresponding delivery system exhibite superior ultrasound visibility and operational performance in both in vitro and animal experiments, indicating strong potential for clinical application.

Yin-Yang theory is one of the core components of the foundational theory of traditional Chinese medicine (TCM), yet its classification as philosophical or scientific has long been controversial. To move beyond the longstanding either-philosophy-or-science debate surrounding Yin-Yang theory in TCM, this article, for the first time, proposes a three-level framework spanning macro, meso, and micro perspectives. At the macro level, Yin and Yang are a theoretical achievement of ancient Chinese natural philosophy, used to explain universal laws governing how the cosmos operates, which constitutes Yin-Yang theory in philosophy; at the meso level, Huangdi Neijing (《黄帝内经》, Inner Canon of Huangdi) translated Yin-Yang from a cosmological framework into medical discourse, making it a core methodological basis for clinical pattern differentiation and treatment, which constitutes Yin-Yang theory in medicine; at the micro level, Yin-Yang theory in TCM has increasingly converged with modern science, showing scientific features that are testable and reproducible, which constitutes Yin-Yang theory in science. The article further demonstrates that Yin-Yang theory in TCM differs markedly from Yin-Yang as a general philosophical doctrine in core application and practical orientation: in the course of its medical transformation, elements related to life phenomena were selectively incorporated, while, within a medical context, abstract propositions such as cosmological speculation were bracketed and rendered concrete, thereby achieving a practice-oriented transition from philosophy to medicine. Based on this, the present study conducts analyses from four aspects, namely philosophical roots, clinical application, modern scientific interpretation, and implications for life sciences; it substantiates the logical basis for Yin-Yang theory in TCM as the overarching framework for clinical pattern differentiation and treatment, reviews modern research progress from perspectives such as systems science and network regulation, and explores its potential value in advancing a new paradigm of state-based medicine. The study suggests that an accurate understanding of Yin-Yang theory in TCM requires moving beyond the either-philosophy-or-science binary and analyzing specific issues on a case-by-case basis. Across different perspectives, Yin-Yang theory in TCM has philosophical, medical, and scientific attributes. Only by grounding the theory in actual clinical efficacy and engaging with modern science can the innovative development of Yin-Yang theory in TCM be promoted, thereby providing valuable Eastern insights for building a life science system with original Chinese contributions.

Objective To explore the mediating role of mindfulness between work immersion and professional well-being in clinical nurses. Methods A total of 477 clinical nurses were selected as the research subjects using the convenience sampling method. The levels of mindfulness, work immersion, and professional well-being among the clinical nurses were surveyed using the Mindful Attention Awareness Scale, the Emergency Department Nurse Work Immersion Experience Questionnaire, and the Medical Workers' Professional Well-being Scale, respectively. A structural equation model was constructed using AMOS 26.0 software. Results The total scores of mindfulness level, work immersion, and professional well-being among clinical nurses were (68.9±11.4), (134.1±20.2), and (89.1±12.6) points, respectively. The total score of mindfulness level was positively correlated with work immersion and professional well-being [correlation coefficients (r) were 0.566 and 0.344, respectively, both P<0.01], and the total score of work immersion was positively correlated with professional well-being (r=0.431, P<0.01). The mediating effect of mindfulness in work immersion and professional well-being was 0.059, with a 95% confidence interval of (0.014-0.108), accounting for 19.5% of the total effect. Conclusion The level of mindfulness among clinical nurses is relatively high. Mindfulness plays a partial mediating role between work immersion and professional well-being.

ObjectiveTo investigate the mechanism of action of Huangqi Guizhi Wuwutang （HGWT） against cerebral ischemia-reperfusion injury （CIRI） based on bioinformatics and experimental validation. MethodsBiological informatics methods were used to screen for active components of HGWT and their targets. The GEO database was utilized to obtain CIRI-related differentially expressed genes （DEGs）， and platforms such as GeneCards were used to identify disease targets. Venn diagram analysis was conducted to identify overlapping targets， followed by protein-protein interaction （PPI）， gene ontology （GO）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis， as well as immune infiltration and immune cell differential analysis. Core genes （Hub genes） were screened using LASSO regression and ROC curves， and molecular docking was used to validate the binding efficiency between the active components of the drug and the core targets. A rat CIRI model was established， with rats randomly divided into five groups （n=10）： Sham surgery group （Sham）， model group （MG）， and low-dose （LD，5.3 g·kg^-1）， medium-dose （MD，10.6 g·kg^-1）， and high-dose （HD，21.2 g·kg^-1） HGWT groups. From 3 days before modeling to 7 days after surgery， oral administration was performed daily： Sham and MG groups received physiological saline， while each drug group received the corresponding dose of HGWT. Hematoxylin-eosin （HE） staining， Nissl staining， and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL staining） were used to assess the repair effects of HGWT on neural damage. Western blot analysis was used to detect B-cell lymphoma-2 protein （Bcl-2）， Bcl-2-associated X protein （Bax）， signal transducer and activator of transcription 3 （STAT3）， phosphorylated STAT3 ［p-STAT3 （Tyr705）］， protein kinase B1 （Akt1）， and phosphorylated Akt1 ［p-Akt1 （Ser473）］， among other target proteins. ResultsAfter screening， 56 common target points of DEGs-disease-drug were obtained. GO and KEGG analyses indicated that HGWT primarily functions in pathways such as apoptosis， oxidative stress， and inflammatory responses. Immune infiltration analysis revealed a significant association between HGWT's anti-CIRI activity and immune cells such as Th17 cells and myeloid-derived suppressor cells （MDSCs） （P0.01）. LASSO-ROC analysis identified Akt1， Caspase-3， glycogen synthase kinase-3β （GSK-3β）， and STAT3 as core genes. Molecular docking confirmed that Hub genes exhibit significant binding affinity with the active components of HGWT （binding energy ≤ -5 kJ·mol^-1）（1 cal≈4.186 J）. Animal experiment results showed that compared with the sham group， the MG group exhibited significant neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brains， with a significant decrease in Nissl body density （P0.01） and increased neuronal apoptosis in rat brains as indicated by TUNEL staining （P0.01）. Compared with the MG， the LD， MD， and HD groups showed reduced neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brain neurons， increased Nissl body density， and reduced apoptosis （P0.01）， with significant differences among the drug groups （P0.01）. Western blot results showed that compared with the sham group， the MG group had reduced Bcl-2 and p-Akt1 （P0.01） and increased Bax and p-STAT3 （P0.01）. Compared with the MG group， the drug groups showed increased Bcl-2 and p-Akt1 （P0.01） and decreased Bax and p-STAT3 （P0.01）. There were no significant changes in total Akt1 and STAT3 protein levels among the groups. ConclusionBased on network pharmacology and experimental verification， HGWT may exert its neuroprotective effects by regulating the phosphorylation levels of Akt1 and STAT3， thereby alleviating cell apoptosis， inflammatory responses， and oxidative stress in rat brain tissue following CIRI. This provides theoretical support for the clinical treatment of CIRI.

The view of youth moral cultivation clearly defines the scope of “morality” and puts forward the requirement of “cultivating morality” for the youth. This is a systematic concept aligned with the main theme of the times and is worth deeply exploring and integrating into the practice of medical ethics education for medical students. With the requirements for innovation and development in medical education， the cultivation of medical students has also been endowed with new connotations. Guided by the connotations of the view of youth moral cultivation and aligned with the objective requirements of medical students’ cultivation， this paper leveraged the core values of traditional Chinese medicine as its entry point. It also explored the realization paths of medical ethics education for medical students that reflect advantages， highlight characteristics， and maintain clear orientation through strengthening the medical ethics education of “dedicated study of medicine，” “honesty and prudence in words and deeds，” “benevolence in heart and skills，” and “doctor-patient trust and harmony，” aiming to cultivate guardians of people’s health with noble medical ethics and superb medical skills.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis