ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6％ in trial group and 83.5％ in control group(P=0.657).The difference between the two groups was 2.11(95％CI-7.19-11.41).Given that the lower confidence limit of the 95％CI was greater than-12％,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5％ in trial group and 77.7％ in control group(P=0.970).The difference between the two groups was-0.21(95％CI-10.95-10.54),with the lower bound of the 95％CI exceeding-12％.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95％CI-10.0-0.1).As the lower limit of the 95％CI exceeded-12％,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7％,6.3％,2.7％and 69.4％in trial group,and 22.3％,4.1％,6.6％ and 66.9％ in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7％ in trial group and 7.1％ in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4％ vs.4.7％,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2％ vs.15.0％,P=0.144).There was no significant difference in the incidence of major bleeding(1.7％ vs.0.8％,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Objective:We investigated the effects of evodiamine(Evo)on the migration,invasion,proliferation,and apoptosis of glio-blastoma(GBM)cells and explored the relevant molecular mechanisms.Methods:Tumor tissue from 26 GBM patients and normal brain tis-sues from 10 patients resected at the Affiliated Hospital of Shandong Second Medical University from February 2022 to February 2024 were retrospectively analyzed.RhoA expression in GBM tissues and its relationship with clinicopathological features in GBM patients were evalu-ated.A-172 and U-118 GBM cells,were used as experimental models.The study included four groups:a control group transfected with empty vector,an Evo group transfected with empty vector and treated with 30 μmol/L Evo,a RhoA group transfected with pcDNA3.1-RhoA,and an Evo+RhoA group given 30 μmol/L Evo and transfected with pcDNA3.1-RhoA.The effect of Evo on the malignant behaviors of A-172 and U-118 cells was analyzed using cell function experiments.Western blot was used to detect the effect of Evo on the protein expressions of RhoA,ROCK,MMP-2 and CyclinD1.Results:RhoA is highly expressed in GBM tissues.Compared with the control group,group Evo signi-ficantly inhibited the proliferation,colony formation,migration and invasion of A-172 and U-118 cells,induced cell apoptosis,and inhibited the protein expression of RhoA,ROCK,MMP-2 and CyclinD1(P<0.05).However,group Evo+RhoA could reverse the effect of Evo on the pro-liferation,migration,invasion and apoptosis of GBM cells,and reverse the inhibitory effect on the expression of related proteins in GBM cells.Conclusions:Evo has been shown to effectively suppress malignant behaviors of GBM cells.The mechanism may be related to the downregulation of RhoA expression.

Objective:We investigated the effects of evodiamine(Evo)on the migration,invasion,proliferation,and apoptosis of glio-blastoma(GBM)cells and explored the relevant molecular mechanisms.Methods:Tumor tissue from 26 GBM patients and normal brain tis-sues from 10 patients resected at the Affiliated Hospital of Shandong Second Medical University from February 2022 to February 2024 were retrospectively analyzed.RhoA expression in GBM tissues and its relationship with clinicopathological features in GBM patients were evalu-ated.A-172 and U-118 GBM cells,were used as experimental models.The study included four groups:a control group transfected with empty vector,an Evo group transfected with empty vector and treated with 30 μmol/L Evo,a RhoA group transfected with pcDNA3.1-RhoA,and an Evo+RhoA group given 30 μmol/L Evo and transfected with pcDNA3.1-RhoA.The effect of Evo on the malignant behaviors of A-172 and U-118 cells was analyzed using cell function experiments.Western blot was used to detect the effect of Evo on the protein expressions of RhoA,ROCK,MMP-2 and CyclinD1.Results:RhoA is highly expressed in GBM tissues.Compared with the control group,group Evo signi-ficantly inhibited the proliferation,colony formation,migration and invasion of A-172 and U-118 cells,induced cell apoptosis,and inhibited the protein expression of RhoA,ROCK,MMP-2 and CyclinD1(P<0.05).However,group Evo+RhoA could reverse the effect of Evo on the pro-liferation,migration,invasion and apoptosis of GBM cells,and reverse the inhibitory effect on the expression of related proteins in GBM cells.Conclusions:Evo has been shown to effectively suppress malignant behaviors of GBM cells.The mechanism may be related to the downregulation of RhoA expression.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.

Objective To observe the efficacy of self-guided attention network for detecting responsible lesions related to cerebral palsy(CP)in children with periventricular white matter injury(PVWMI).Methods Totally 383 children with PVWMI were retrospectively enrolled and divided into CP group(n=243)and non-CP group(n=140),while 214 children without obvious brain abnormality on brain MRI were taken as control group.ROI of 4 key anatomical structures related to CP,i.e.centrum semiovale,posterior limb of internal capsule,cerebral peduncle and thalamus were delineated on T1WI,while responsible lesions related to CP within the key anatomical structures were labeled on T2WI,and the images were then registrated and used as input of the networks.ResNet34 network was adopted combined with attention and self-guided networks to train the network for detecting responsible lesions related to CP in children with PVWMI,and their efficacies were evaluated.The optimal network was screened,and its efficacy for segmenting the key anatomical structures was evaluated.Results Self-guided attention network was the optimal network,its area under the curve(AUC)for detecting lesions was 0.794-0.914,and the Dice similarity coefficient for segmenting the key anatomical structures was 0.702-0.764.Conclusion Self-guided attention network could be used for preliminarily detecting responsible lesions related to CP in children with PVWMI.

OBJECTIVE To explore the efficacy of low temperature plasma(LTP)in treatment of the rats with Pseudomonas aeruginosa(PA)wound infection.METHODS Totally 20 SD rats were assigned to establish the PA wound infection models and were randomly divided into the LTP group with 10 rats and the air control group with 10 rats.The wound healing dynamics,bacterial loading capacity,histopathology,levels of cytokines and microen-vironment features were observed during the healing process.RESULTS LTP accelerates the healing of PA infec-tion wound,the wound area reduced after the treatment for 3 days,and the inflammatory reactions alleviated;the infection symptoms subsided after the treatment for 7 days,and the wounds became dry and scabbed;the wounds reduced in size by day 15,showing favorable healing trends.Repeated measurement analysis of variance(ANOVA)indicated that there was significant difference in the impact of LTP on the covering rate of wounds(Ftime=10.230,P＜0.001;Fbetween-group=11.340,P=0.001;Finteraction=2.890,P=0.042).The result of quantitative bacterial loads analysis showed that the bacterial loads of the LTP group were lower than those of the control group after the treatment for 3,7 and 15 days(P＜0.05).The result of histopathology indicated that the infiltra-ted wound inflammatory cells of the LTP group reduced,the collagen fibers were well-aligned,and the neovascu-larization and formation of granulation tissues were evident.In addition,the pH value of wound tissues and reac-tive oxygen species(ROS)level were improved after the treatment with LTP,which was matched with the process of wound healing.The result of cytokines test showed that LTP could upregulate the levels of VEGF and TGF-β1,downregulate the levels of IL-1β and TNF-α,and promote the wound healing,with statistically signifi-cant differences observed(P＜0.05).CONCLUSION LTP may facilitate the control of infections by reducing the bacterial colony counts,establish the effective microenvironment for tissue healing,and accelerate the healing of wounds with PA infection by regulating the release of healing-related cytokines.

Objective To investigate the relationship between quantitative parameters of the histogram of global fat fraction(FF)in the infrapatellar fat pad(IPFP)and the severity of knee osteoarthritis(KOA).Methods A total of 120 patients were prospectively selected and divided into the non-KOA group(KL grade 0-1),the mild KOA group(KL grade 2),and the severe KOA group(KL grade 3-4)based on the Kellgren-Lawrence(KL)classification criteria of knee X-rays.The FF maps of the IPFP were obtained based on the mDIXON-Quant technique.The region of interest(ROI)was delineated using 3D Slicer software,and global histogram analysis was performed to obtain quantitative parameters,including mean,median,10th percentile(10th),90th percentile(90th),skewness,kurtosis,and entropy.Pearson or Spearman correlation analysis was used to evaluate the correlation between each quanti-tative parameter and the severity of KOA.The diagnostic efficacy was analyzed using the receiver operating characteristic(ROC)curves.Results As the progression of KL classification,the mean,median,percentiles,and kurtosis of the global FF histogram quantitative parameters in the IPFP decreased,while skewness and entropy increased,with statistically significant among the three groups(P＜0.001).The mean,median,10th,90th,and kurtosis showed negative correlations with the KL classification(r=-0.563,-0.448,-0.614,-0.294,-0.450),while skewness and entropy showed positive correlations with the KL classification(r=0.385,0.637),all of which were statistically significant(P＜0.05).The area under the curve(AUC)for diagnosing KOA were 0.799,0.725,0.828,0.636,0.741,0.688,and 0.830,respectively.The sensitivity of the 10th and entropy were 74.4％and 77.9％,respectively,and the specificity were 85.3％and 88.2％,respectively.Conclusion The quantitative parameters of the histogram of global FF in the IPFP are correlated with the severity of KOA and can reflect the pathophysiological changes in the IPFP.They can serve as objective indicators for diagnosing KOA and assessing its severity.