SPF chickens were immunized with HN-mRNA vaccine by intramuscular injection.He-magglutination inhibition(HI)test,lymphocyte proliferation test,RT-qPCR and pathological sec-tions were used to evaluate the humoral and cellular immunity and protection against challenge in-duced by the candidate HN-mRNA vaccine.The results showed that 2.5,5.0,and 7.5 μg HN-mR-NA induced HI antibody antibodies in a dose-dependent manner.Among them,the Hi antibody in-duced by 7.5 μg HN-mRNA was slightly higher than that of the weak toxic vaccine(La Sota strain).In addition,in response to the stimulation of inactivated NDV virus,the proliferation and activation of lymphocytes in 2.5,5.0 and 7.5 μg HN-mRNA immunization groups and commercial vaccine group were observed.To further evaluate the antiviral protection provided by HN mRNA immunization,the 105 ELD50 NDV strong strain NA-1 was used to attack the 7.5 μg HN-mRNA immunised group and the commercial weakened vaccine(La Sota strain)and PBS groups using na-sal and ocular drops.The results showed that the survival rate of 7.5 μg HN-mRNA immunization group and commercial vaccine group was 100％,and these vaccines could protect tissues and or-gans from the damage caused by virus infection.At the same time,7.5 μg HN-mRNA and commer-cial vaccine could shorten the time of virus shedding in vitro and the viral load in vivo.This study provides a foundational framework for the clinical application of NDV HN mRNA candidate vac-cines and offers insights for the development of novel mRNA vaccines for poultry.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

Objective To investigate the role of ginsenoside Rh1 in regulating the changes of characteristic differential metabolites in rat models of exercise-induced fatigue by gas chromatography-mass spectrometry(GC-MS)and multidimensional statistical analysis,and to clarify the metabolic pathways,so as to provide experimental basis and theoretical support for the effective alleviation of exercise-induced fatigue through Rh1.Methods A total of 27 SPF SD rats were randomly divided into blank control group,model group,and ginsenoside Rh1 group,with 9 rats in each group.A rat exercise-induced fatigue model was established by treadmill exercise.After blood sampling,GC-MS technology,Principal Component Analysis(PCA)and Orthogonal Partial Least Squares(PLS-DA)were used for the identification and screening of differential metabolites,which were further structurally identified in KEGG and HMDB databases.MetPA database was used to construct metabolic pathways and enrich for topological analysis.Results The time to exhaustion in the ginsenoside Rh1 group was significantly longer than that in the model group.Significant differential expression of 8 metabolites(6 significantly decreased and 2 significantly increased)was found in the model group as compared to the blank control group,and 5 metabolic pathways were involved.In the ginsenoside Rh1 group,there were 3 metabolites with significant changes compared with the model group.Citric acid and fatty acid were significantly increased,α-D-glucosamine 1-phosphate was decreased,and the main pathway involved was tricarboxylic acid cycle.Conclusion Rh1 can significantly prolong the time to exhaustion and relieve exercise-induced fatigue in rats,which is closely related to the metabolic pathway of tricarboxylic acid cycle.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis(UC)mice based on adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)pathway.METHODS Male BALB/c mice were randomly divided into control group,model group,inhibitor group(AMPK inhibitor Compound C 20 mg/kg),paeoniflorin low-,medium-and high-dose groups(paeoniflorin 12.5,25,50 mg/kg),high-dose of paeoniflorin+inhibitor group(paeoniflorin 50 mg/kg+Compound C 20 mg/kg),with 8 mice in each group.Except for the control group,mice in all other groups were given 4%dextran sulfate sodium solution for 5 days to establish the UC model.Subsequently,mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally,once a day,for 7 consecutive days.The changes in body weight of mice were recorded during the experiment.Twenty-four hours after the last administration,colon length,malondialdehyde(MDA)content,and activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in colon tissues were measured;histopathological morphology of colon tissues,tight junctions between intestinal epithelial cells,and histopathological scoring were all observed and evaluated;the mRNA expressions of AMPK and Nrf2,as well as the protein expressions of heme oxygenase-1(HO-1),occludin and claudin-1,were all determined in colon tissue.RESULTS Compared with model group,paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue,as well as improved tight junction damage between intestinal epithelial cells.Additionally,significant increases or upregulations were observed in body weight,colon length,activities of SOD and GSH-Px,phosphorylation level of AMPK,and protein expression of Nrf2,HO-1,occludin,claudin-1,and mRNA expressions of AMPK and Nrf2;concurrently,MDA content and histopathological scores were significantly reduced(P＜0.05 or P＜0.01).In contrast,the inhibitor group showed comparable(P＞0.05)or worse(P＜0.05 or P＜0.01)indicators compared to the model group.Conversely,the addition of AMPK inhibitor could significantly reverse the improvement of high-dose paconiflorin(P＜0.01).CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice,improve tight junctions between epithelial cells,upregulate the expression of related proteins,and promote the expression and secretion of antioxidant-promoting molecules,thereby ameliorating UC;its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

SPF chickens were immunized with HN-mRNA vaccine by intramuscular injection.He-magglutination inhibition(HI)test,lymphocyte proliferation test,RT-qPCR and pathological sec-tions were used to evaluate the humoral and cellular immunity and protection against challenge in-duced by the candidate HN-mRNA vaccine.The results showed that 2.5,5.0,and 7.5 μg HN-mR-NA induced HI antibody antibodies in a dose-dependent manner.Among them,the Hi antibody in-duced by 7.5 μg HN-mRNA was slightly higher than that of the weak toxic vaccine(La Sota strain).In addition,in response to the stimulation of inactivated NDV virus,the proliferation and activation of lymphocytes in 2.5,5.0 and 7.5 μg HN-mRNA immunization groups and commercial vaccine group were observed.To further evaluate the antiviral protection provided by HN mRNA immunization,the 105 ELD50 NDV strong strain NA-1 was used to attack the 7.5 μg HN-mRNA immunised group and the commercial weakened vaccine(La Sota strain)and PBS groups using na-sal and ocular drops.The results showed that the survival rate of 7.5 μg HN-mRNA immunization group and commercial vaccine group was 100％,and these vaccines could protect tissues and or-gans from the damage caused by virus infection.At the same time,7.5 μg HN-mRNA and commer-cial vaccine could shorten the time of virus shedding in vitro and the viral load in vivo.This study provides a foundational framework for the clinical application of NDV HN mRNA candidate vac-cines and offers insights for the development of novel mRNA vaccines for poultry.

Objective To study the effects of different posterior slope installations of unicompartmental knee arthroplasty(UKA)prostheses on the loading and motion of the knee joint and insert wear.Methods A combined approach involving the UKA musculoskeletal multibody dynamic,finite element,and wear prediction models was used to investigate the effects of five different posterior slope installation positions of the UKA prosthesis on the postoperative knee joint force and motion,insert contact stress,linear wear depth,and wear volume.Results At a 0° posterior slope,the maximum von Mises stress of the insert was 24.84 MPa,maximum contact stress was 47.61 MPa,and volumetric wear after 5 million cycles(MC)was 47.29 mm3.As the posterior slope angle of the UKA prosthesis increased,the internal rotation and posterior translation during the gait cycle increased,the medial joint force during the swing phase increased,the von Mises and contact stresses of the insert after 5 MC decreased significantly,and the wear area,maximum linear wear depth,and volumetric wear volume of the insert were consequently reduced.Compared to the 0° posterior slope,the linear wear depths of the insert at the 3°,5°,and 7° posterior slopes decreased by 17.8％,19.2％,and 20.6％,respectively.The volumetric wear volumes of the inserts decreased by 24.5％,30.9％,and 34.3％,respectively.Conclusions Installing a UKA prosthesis with a posterior slope exceeding 3° significantly increases internal rotation and posterior translation during the gait cycle,further reducing the articular volumetric wear of the polyethylene insert.

With the further development and long-term follow-up of endovascular treatment for aortic diseases, increasing evidence shows that in many cases, there are difficulties in the diagnosis of causes, decision-making of treatment timing, and lack of effective evaluation of treatment prognosis in endovascular treatments. Therefore, it is necessary to conduct in-depth research on non-invasive treatment including prevention, diagnosis, treatment, and prediction of aortic diseases. The non-invasive treatment of aortic disease is mainly applied to high-risk populations with aortic dissection, regulating key targets and mechanisms, and adopting drug intervention in advance to achieve the goal of controlling aortic dilation and preventing the occurrence of dissection. It also conducts precise multi omics analysis to determine the optimal intervention timing and treatment strategy, and aims at complications related to aortic disease or endovascular treatment for patients with a positive family history of aortic dilation and those who have developed aortic dissection. Precise regulation can control the progression of aortic aneurysm and aortic dissection, delay or achieve long-term stable coexistence with aortic disease, and even reverse disease progression and achieve benign aortic remodeling through new intervention vectors. Ultimately achieving the ideal state of complete thrombosis and mechanized healing of the aortic aneurysm or aortic dissection false lumen.

The aim of this study is to investigate the effect of Dahuang Fuzi decoction(DHFZT)on the killing effect of natural killer(NK)cells and the growth of lung cancer xenografts in mice.Lewis lung cancer xenograft model was constructed,and the mice were randomly divided to the normal saline group,low and high concentrations of DHFZT groups.The growth of lung cancer xenografts in mice in the control group,low and high concentration of DHFZT treatment groups was detected.The levels of IFN-y,IL-2 and IL-10 were detected by ELISA.The killing effect of NK cells was detected by calcein release assay.The release of CD107α was detected by flow cytometry.The expression of activated receptors and the tumor cell surface ligands were detected in the con-trol group and DHFZT treatment groups.The results showed that the xenografts of Lewis mice in the DHFZT treatment groups were grown slower than that in the control group in a dose depend-ent manner(P＜0.05).Compared with the control groups,the levels of IL-2 and IFN-y in tumor tissues were increased in DHFZT treatment groups(P＜0.05),but no significant changes in IL-10.Calcein release assay showed that the killing efficiency of NK cells in the DHFZT treatment groups was increased(P＜0.05).The secretion level of IFN-y in the culture supernatant was increased by DHFZT treatment(P＜0.05).DHFZT treatment increased the expression level of CD107α of NK cells.The expression of MIC A/B on the surface of A549 and H1299 cells was up-regulated by DHFZT treatment,but not the expression of inhibitory ligand HLA-ABC.The results showed that DHFZT enhanced the killing effect of NK cells on mouse lung cancer cells by up-reg-ulating the expression of MIC A/B,increasing the secretion of IFN-y and CD107α.Hence,these re-sults indicated that DHFZT suppresses the lung cancer growth potential through regulating the killing effect of NK cells.