ObjectiveTo investigate the effects of exogenous nitric oxide （NO） on the accumulation and quality formation mechanism of flavonoids in Scutellariae Radix. MethodsFresh roots of Scutellaria baicalensis were treated with sodium nitroprusside （SNP） solutions at concentrations of 0.0， 7.5， and 20 mmol·L^-1， respectively. Kits and supporting reaction systems were used to determine the following indicators of samples in each group， including （1） reactive oxygen species： changes in the content of nitric oxide （NO）， superoxide anion （O2-·）， and hydrogen peroxide （H₂O₂）， （2） lipid oxidation products： changes in the content of malondialdehyde （MDA）， （3） antioxidant enzymes： changes in the activity of superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）， and （4） metabolic key enzymes and metabolic intermediates： Changes in the activity of phenylalanine ammonia-lyase （PAL） and the content of 1，3-diphosphoglycerate （1，3-DPG）. High-performance liquid chromatography （HPLC） was used to determine the changes in the content of secondary metabolites in flavonoids such as baicalin， wogonoside， baicalein， and wogonin in each group. ResultsCompared with that on day 0， during the treatment with 20 mmol·L^-1 SNP solution， the content of NO， O2-·， H₂O₂， and MDA in fresh roots of Scutellaria baicalensis increased significantly （P<0.01）， by 138.7%， 75.7%， 292.9%， and 140.3% respectively. The activity of SOD， CAT， and POD increased by 100.7%， 41.4%， and 70.4% respectively （P<0.01）， and that of PAL increased by 111.1% （P<0.01）. The content of the secondary metabolites baicalin and wogonoside remained basically unchanged， while that of baicalein and wogonin increased by 401.3% and 457.9% respectively （P<0.01）. The content of 1，3-DPG increased by 165.0% （P<0.01）. In the 7.5 mmol·L^-1 SNP solution treatment group， the stress degree was relatively mild. Compared with that on day 0， the content of NO， O2-·， H₂O₂， and MDA increased by 76.2%， 57.7%， 221.4%， and 99.7% respectively （P<0.01）. The activity of antioxidant enzymes SOD， CAT， and POD increased by 79.5%， 55.6%， and 51.9% respectively （P<0.01）， and that of PAL increased by 69.0% （P<0.01）. The content of baicalein and wogonin increased by 204.7% and 272.2% respectively （P<0.01）， and that of 1，3-DPG increased by 128.0% （P<0.01）. The 20 mmol·L^-1 SNP group showed better performance than the 7.5 mmol·L^-1 SNP group. ConclusionSNP can simulate the physiological state of Scutellaria baicalensis under stress conditions， activate the antioxidant protection mechanism， promote the biosynthesis of flavonoids in Scutellariae Radix， and significantly improve the quality of medicinal materials in Scutellariae Radix.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

OBJECTIVE: To investigate the effects of combined platelet-rich plasma (PRP) and arterial supercharging technique on the survival rate and functional restoration of cross-body region skin flaps in rabbits. METHODS: Twelve healthy 6-month-old New Zealand White rabbits were randomly assigned to 4 groups ( n=3): sham group, PRP group, anastomosis group, and combined treatment group. An axial skin flap with an area of 12 cm×6 cm on the inner side of the hind limbs of all animals were prepared, with the saphenous artery as the main blood supply. Following the ligation of both the proximal and distal ends of the saphenous artery across all groups, the sham group received no further intervention, the PRP group was subjected to PRP injection, the anastomosis group underwent in situ end-to-end anastomosis of the distal saphenous artery, and the combined treatment group received both in situ distal saphenous artery anastomosis and PRP administration. Flap survival was evaluated and recorded on postoperative days 1, 3, and 7, with survival rates calculated accordingly. On day 7, flap tissue samples were harvested for HE staining to assess basal tissue morphology. Additionally, immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and CD31 in the flap tissues. RESULTS: At postoperative day 1, no significant difference in flap survival rates were observed among the 4 groups ( P>0.05). At day 3, the PRP group showed no significant difference compared to the sham group ( P>0.05); however, both the anastomosis and combined treatment groups exhibited significantly higher survival rates than the sham group ( P<0.05), the combined treatment group further demonstrated superior survival rates compared to both the PRP and anastomosis groups ( P<0.05). At day 7, the combined treatment group maintained significantly higher survival rates than all other groups ( P<0.05), while both the PRP and anastomosis groups exceeded the sham group ( P<0.05). HE staining at day 7 revealed persistent inflammatory cell infiltration, sheet-like erythrocyte deposition, and disordered collagen fibers in the sham group. The PRP group showed nascent microvessel formation and early collagen reorganization, whereas the anastomosis group displayed mature microvasculature with resolved interstitial edema. The combined treatment group exhibited differentiated microvessels with densely packed collagen bundles. Immunohistochemical analysis at day 7 demonstrated significantly larger relative area percentages of α-SMA, VEGF, and CD31 positive cells in the combined treatment group compared to all other groups ( P<0.05). Both the PRP and anastomosis groups also showed significantly higher values than the sham group ( P<0.05). CONCLUSION The combination of PRP and arterial supercharging techniques significantly enhances flap healing, potentially through mechanisms involving augmented angiogenesis and improved blood supply.
Animals ; Rabbits ; Platelet-Rich Plasma ; Surgical Flaps/blood supply* ; Graft Survival ; Anastomosis, Surgical/methods* ; Ischemia/surgery* ; Arteries/surgery* ; Skin/blood supply* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Skin Transplantation/methods*

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Objective Based on the Ancient and Modern Medical Case Cloud Platform V2.3.7,analyze the medication pattern and mechanism of action of Chinese medicines commonly used in famous medical cases for the treatment of Alzheimer's disease(AD).Methods The core Chinese medicines for AD were screened according to the inclusion and exclusion criteria by searching the famous Chinese medicine cases in the platform,then established the disease-core Chinese medicines-active ingredients-common targets network.The protein-protein interaction network(PPI)was established through the common targets.Gene oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed by David platform.Molecular docking and dynamics simulations were employed to evaluate the binding affinity and stability between key targets and active ingredients.Results Data mining was performed on all the famous medical cases from the time of database construction to October 2023,and the results were summarized as follows.The high-frequency regulating Qi medications and tonifying Qi medications were Citri Reticulatae Pericarpium and Aurantii Fructus Immaturus;Panax ginseng,Ziziphi Jujubae Fructus,Codonopsis pilosula,Astragali Radix,Atractylodis Macrocephalae Rhizoma,Dioscoreae Rhizoma,and Glycyrrhizae Radix et Rhizoma.The core herbs contained 778 active ingredients and 377 targets;1986 disease targets;79 common targets were obtained after intersection with AD targets,and 7 core targets were identified through PPI network topology analysis,including TNF,AKT1,TP53,PPARG,etc.GO and KEGG pathway enrichment analyses confirmed that the targets of the active ingredients of the core herbs involved 138 pathways,and the core herbs could regulate chemical carcinogenesis-receptor activation、serotonergic synapse、chemical carcinogenesis-reactive oxygen species pathways to treat AD.Molecular docking and molecular dynamics simulation results showed good binding ability and stability between the key targets and the core components.Conclusion Through data mining to analyze the core herbs for the treatment of AD,the present investigation showing the pharmacological mechanism of 12-O-Nicotinoylisolineolone and Odoratin in the treatment of Alzheimer's disease at the molecular level,lay a certain theoretical foundation of 12-O-Nicotinoylisolineolone and Odoratin in the future.

Objective To explore whether miR-146b can participate in the brain injury process of diabetic rats with cerebral infarction(DM-CI)by regulating the extracellular regulatory protein kinase(ERK1/2)-activated protein-1(AP-1)signaling pathway.Methods 80 SD rats were randomly divided into sham operation group,DM-CI group,low miR-146b expression group and ERK1/2 inhibition group,with 20 rats in each group.The National Institutes of Health Stroke Scale(NIHSS)score measures brain function in rats.The mRNA levels of miR-146b,ERK1/2 and AP-1 in rat brain tissue were detected by RT-qPCR.Western blotting detected ERK1/2,AP-1 protein levels in rat brain tissue.TTC staining was used to detect cerebral infarction volume in rats.H&E staining was used to detect brain histopathological changes.Random blood glucose levels were detected by glucose meter in rats.Results Compared with sham operation group,mRNA expression levels of miR-146b,ERK1/2 and AP-1 in brain tissue of rats in DM-CI group were significantly increased,with statistically differences(t=10.86,15.62,9.87,all P<0.05).ERK1/2 and AP-1 protein levels increased,with statistically differences(t=11.18,23.81,P<0.05).NIHSS score increased and random blood glucose level increased(t=44.49,30.02,all P<0.05),and increased cerebral infarction volume(t=51.05,P<0.05),the structure of brain tissue was disorganized and loose,and edema can be seen in the pericellular space.Compared with the DM-CI group,the mRNA expression levels of miR-146b,ERK1/2 and AP-1 in the brain tissue of rats with low expression of miR-146b were decreased,with statistically differences(t=38.00,20.03,24.25,all P<0.05).the protein expression of EPK1/2 and AP-1 decreased,and the differences were statistically significant(t=12.30,26.70,all P＜0.05).NIHSS score and random blood glucose level were decreased,with statistically differences(t=38.11,33.77,all P<0.05),cerebral infarction volume decreased(t=16.70,P<0.05),the degree of brain tissue in jury and edema was improved,and the expression levels of ERK1/2 and AP-1 protein and mRNA in brain tissue of rats inhibited by ERK1/2 were decreased,with statistically differences(t=13.61～38.00,all P<0.05),the NIHSS score of rats was decreased,and the random blood glucose level was decreased,with statistically differences(t=16.48,26.61,all P<0.05).Conclusion MiR-146b may be involved in brain functional and structural damage in DM-CI rats by regulating ERK1/2-AP-1 signaling pathway.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Objective:To investigate the alterations of individual metabolic brain network properties in patients with mild cognitive impairment (MCI) and their correlations with cognitive function.Methods:One hundred and five participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) database enrolled from March 2012 to February 2016 were chosen, including 61 MCI patients and 44 normal controls (NC). Cognitive assessments, including mini-mental state examination (MMSE), auditory verbal learning test (AVLT), trail making test (TMT), and semantic verbal fluency (SVF) score, were performed in both groups; differences of above scores and clinical data between the participants from the two groups were compared. T1-weighted imaging and fluorodeoxyglucose positron emission tomography (FDG-PET) images were collected in both groups; individual metabolic brain networks were constructed based on differences in effect sizes between brain regions and network properties were calculated. Spatial correlation analysis was used to compare the correlations of metabolic brain networks at the individual and group levels. General linear model was employed to compare the differences in network properties between the two groups. Partial correlation analysis was used to examine the correlations of differential network properties with cognitive function in MCI patients. A support vector machine (SVM) classification model was constructed based on individual metabolic brain network properties, and receiver operating characteristic (ROC) curve was used to explore the diagnostic value of this SVM classification model in MCI.Results:(1) Compared with the NC group, the MCI group had significantly lower MMSE and AVLT-immediate recall scores, and longer TMT-A completion time ( P<0.05). (2) Spatial correlation analysis revealed a positive correlation between individual metabolic brain networks and group-level metabolic brain networks in patients of the MCI group ( r=0.825, P<0.001). No significant differences in global network properties were noted between the two groups ( P>0.05). Compared with the NC group, the MCI group significantly decreased degree centrality in the left A8vl, right A39c, and right V5/MT+ regions, increased degree centrality in the left anterior cuneus, decreased nodal efficiency in the left A8vl, right V5/MT+, and right caudal hippocampus regions, increased nodal shortest path length and nodal clustering coefficient in the left A8vl region ( P<0.05). (3) The degree centrality at the A8vl of ventral part of the left middle frontal gyrus and nodal efficiency in right caudal hippocampus region were positively correlated with AVLT-immediate recall scores ( r=0.331, P=0.010; r=0.282, P=0.030), nodal efficiency in the left A8vl region was negatively correlated with TMT-A completion time ( r=-0.470, P<0.001), and nodal efficiency in the left A8vl region was positively correlated with SVF score ( r=0.263, P=0.044). (4) Area under the curve of SVM classification model in diagnosing MCI was 0.880 (95% CI: 0.813-0.945, P<0.001), with an accuracy rate of 0.790. Conclusions:Patients with MCI have alterations in individual metabolic brain network properties, among which the degree centrality and nodal efficiency of some nodes are closely related to cognitive function changes. Models constructed based on individual metabolic brain network properties can help to effectively diagnose MCI.

Objective To analyze the association between plasma circulating tumor DNA(ctDNA)TP53 mutation status and survival outcomes in breast cancer patients.Methods PubMed,Embase,and the Cochrane Library were searched for relevant literature published between 2000 and 2025,examining the impact of plasma ctDNA TP53 mutations on survival outcomes in breast cancer patients,including overall survival(OS),progression-free survival(PFS),or disease-free survival(DFS).Two researchers independently screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data.The Newcastle-Ottawa scale and Cochrane Risk of Bias Assessment Tool were used to evaluate study quality.Meta-analysis,publication bias assessment,and sensitivity analysis were performed using Review Manager 5.3 and STATA 18.0 software.Results A total of 14 studies(13 cohort studies and 1 randomized controlled trial)in-volving 3521 breast cancer patients were included,among whom 921 had TP53 mutations.All studies were as-sessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS(I2=77%,HR=1.82,95%CI:1.15-2.88,P=0.010),PFS(I2=63%,HR=1.68,95%CI:1.30-2.17,P＜0.001),and DFS(I2=85%,HR=1.98,95%CI:1.05-3.75,P=0.040).Funnel plots indicated no significant publication bias,and sensitivity analysis confirmed the stabil-ity and reliability of the results.Subgroup analyses based on study design,breast cancer stage and molecular subtype revealed that TP53 mutations were associated with worse prognosis in prospective studies(OS:HR=2.32,95%CI:1.84-2.92,P＜0.001;PFS:HR=1.83,95%CI:1.47-2.27,P＜0.001),metastatic/ad-vanced breast cancer(OS:HR=2.03,95%CI:1.44-2.87,P＜0.001;PFS:HR=1.90,95%CI:1.57-2.31,P＜0.001),and hormone receptor-positive and human epidermal growth factor receptor 2-negative(HR+HER2-)patients(OS:HR=2.11,95%CI:1.56-2.85,P＜0.001;PFS:HR=1.94,95%CI:1.62-2.33,P＜0.001).Among different treatment regimens,patients with TP53 mutations receiving trastuzumab combined with paclitaxel exhibited relatively better prognosis(PFS:HR=0.08,95%CI:0.02-0.30,P＜0.001).Conclusion Plasma ctDNA TP53 mutations are closely associated with survival outcomes in breast cancer patients and may serve as a potential predictor of poor prognosis,providing support for clinical manage-ment and prognostic assessment.