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.

Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba（TPAGH）， and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group， recombinant human epidermal growth factor（rhEGF） group（4 mg·kg^-1）， and low， medium， and high dose groups of TPAGH（3.5， 7， 14 mg·kg^-1）， with 24 mice in each group. A full-thickness skin excision model was constructed， and each administration group was coated with the drug at the wound site， and the model group was treated with an equal volume of normal saline， the treatment was continued for 30 days， during which 8 mice from each group were sacrificed on days 6， 12， and 30. The healing of the wounds in the mice was observed， and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin（HE）， Masson， and Sirius red staining， and enzyme-linked immunosorbent assay（ELISA） was used to dynamically measure the contents of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， vascular endothelial growth factor A（VEGFA）， matrix metalloproteinase（MMP）-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH， and molecular docking of key components and targets was performed. Gene Ontology（GO） biological process analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out for the related targets， so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH， including 28 phenylpropanoids， 31 tannins， 23 triterpenes， 49 flavonoids， and 15 others， and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that， compared with the model group， the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate（P<0.05）， and the number of new capillaries， number of fibroblasts， number of new skin appendages， epidermal regeneration rate， collagen deposition ratio， and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved（P<0.05， 0.01）， the levels of IL-6， TNF-α， MMP-3 and MMP-9 in the skin tissues were reduced to different degrees， while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets， including tumor protein 53（TP53）， sarcoma receptor coactivator（SRC）， protein kinase B（Akt）1， signal transducer and activator of transcription 3（STAT3）， epidermal growth factor receptor（EGFR） and so on， participating in 75 signaling pathways such as advanced glycation end-products（AGE）-receptor for AGE（AGE/RAGE） signaling pathway， phosphatidylinositol 3-kinase（PI3K）/Akt signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway. Molecular docking confirmed that the key components genistein， geraniin， and casuariin had good binding ability to TP53， SRC， Akt1， STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction， thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology， the study explores how key components may bind to targets such as TP53， Akt1 and EGFR， exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.

Objective : To explore the factors influencing the efficacy of first-generation EGFR tyrosine kinase inhibitors(EGFR-TKIs) in patients with EGFR-mutated advanced lung adenocarcinoma and to construct and validate a corresponding nomogram prediction model. Methods : A total of 220 patients with EGFR-mutated advanced lung adenocarcinoma treated with icotinib were enrolled and randomly divided into a training group(154 cases) and a validation group(66 cases) in a 7 ∶3 ratio. Cox regression analysis was performed to identify factors affecting the efficacy of first-generation EGFR-TKIs in the training group. A prediction model was constructed, and calibration curves and receiver operating characteristic(ROC) curves were plotted to validate the model′s performance. Results: In the training group, the objective response rate was 35.71%, the disease control rate was 77.27%, the median progression-free survival(PFS) was 12.5 months, the median overall survival was 18 months, the 2-year OS rate was 66.23%, and the PFS rate was 42.21%. Univariate analysis showed that brain metastasis, bone metastasis, TNM stage, differentiation degree, neutrophil-to-lymphocyte ratio(NLR), post-treatment p53 levels, p53 difference(Δp53), post-treatment cancer antigen gene(CAGE) levels, and CAGE difference(ΔCAGE) were associated with PFS(P2=4.429, P=0.351). ROC curve analysis in the training group showed that the nomogram model had a sensitivity of 80.00%, specificity of 77.53%, and AUC of 0.864 for predicting therapeutic efficacy, while the validation group showed a sensitivity of 74.08%, specificity of 71.43%, and AUC of 0.835. Conclusion Changes in lung cancer autoantibodies(Δp53 and ΔCAGE), TNM stage, and NLR are key factors influencing the efficacy of first-generation EGFR-TKIs in EGFR-mutated advanced lung adenocarcinoma. The nomogram prediction model based on p53 and CAGE demonstrates good predictive performance.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Objective To investigate the effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.

Objective To investigate the adverse pregnancy outcomes of fetuses with increased nuchal translucency(NT).Methods A total of 376 pregnant women at the Third Affiliated Hospital of Zhengzhou University from May 2023 to January 2024 were selected as research subjects,who had a diagnosis of fetal NT ≥ the 95th percentile and complete pregnancy outcomes for singleton pregnancies.The fetuses were divided into simple thickening group(n=320)and thickening with structural abnormalities group(n=56)based on NT ultrasound results.The interventional prenatal diagnosis outcomes and pregnancy outcomes of two groups were compared.Results The rate of chromosomal abnormalities and the incidence of adverse pregnancy outcomes were higher in thickening with structural abnormalities group compared to simple thickening group with statistically significant differences(P＜0.05).The overall incidence of adverse pregnancy outcomes in NT thickened fetuses was 31.65％,but after excluding chromosomal abnormalities and structural malformations,the good pregnancy outcome rate in NT thickened fetuses was 98.09％.Conclusion NT thickening is associated with adverse pregnancy outcomes in fetuses,and the risk of poor fetal outcome is further increased when NT thickening combined with structural abnormalities in early pregnancy,but the pregnancy outcome is better in fetuses with NT thickening after excluding chromosomal abnormalities and structural malformations.

Objective:To examine the dynamic interactive relationships between cyberbullying perpetration,anxiety,and depression in college students.Methods:A total of 4 148 college students from a comprehensive uni-versity in Guangxi Zhuang Autonomous Region completed self-report measures including Cyberbullying Scale(CS),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)at two time points,18-month a-part.Results:Correlation analysis showed significant concurrent(r=0.11-0.17,Ps＜0.001)and lagged(r=0.06-0.44,Ps＜0.001)positive associations among CS,SAS,and SDS scores.Cross-lagged analysis,controlling for gender and age,indicated that T1 CS scores were positively associated with T2 SAS and SDS scores(β=0.13,0.14,Ps＜0.001).Additionally,SAS scores at T1 and SDS scores at T1 were positively associated CS scores at T2,respectively(β=0.07,0.05,Ps＜0.001).Conclusion:Cyberbullying perpetration,anxiety,and depression in-fluence each other over time among college students,suggesting a reinforcing negative cycle.