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

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVES: We aimed to compare the apical sealing properties of three endodontic sealers, namely, C-Root SP (C-R), iRoot SP, and GuttaFlow Bioseal (GFB) in vitro. METHODS: Eighty-two single-rooted premolars and anterior teeth were prepared by using M3 machine with nickel-titanium file and randomly divided into six experimental groups (n=12) and two control groups (n=5). Group A1: single-cone technique (SC)+C-R; group B1: SC+iRoot SP; group C1: SC+GFB; group A2: single-cone with ultrasonic activation (SU)+C-R; group B2: SU+iRoot SP; group C2: SU +GFB; group D: positive control group, and group E: negative control group. Dye penetration length and lateral root canal filling in each group were measured by dye penetration test. A scanning electron microscope (SEM) was used to observe the interface between gutta pertscha, root canal sealer, and dentin wall. Dye penetration length was measured and analyzed by Kruskal-Wallis test, and data on lateral root canal filling were evaluated using Chi-square. RESULTS: The dye penetration length in group A1 was lower than that in groups C1 and A2 (P<0.05) but was not significantly different from the other groups (P>0.05). Lateral root canal filling was not significantly different among all groups (P>0.05). SEM showed that GFB was slightly better than C-R and iRoot SP in binding to gutta pertcha and dentin wall. CONCLUSIONS GFB, C-R, and iRoot SP demonstrate excellent apical sealing ability. Under the conditions tested in this study, SU did not yield significantly improve the apical sealing ability of the three root canal sealers.
Root Canal Filling Materials/chemistry* ; Humans ; Gutta-Percha ; Microscopy, Electron, Scanning ; Root Canal Obturation/methods* ; Ceramics ; Dimethylpolysiloxanes ; Drug Combinations

OBJECTIVES: This study aimed to evaluate the filling effects of three biomaterial root canal sealers [iRoot SP, C-Root SP, and GuttaFlow Bioseal (GFB)] by using Micro-CT. METHODS: Sixty single-canal detached premolars were selected. After crown amputation, their uniform working length was set at 12 mm and prepared to a 06 taper 30# with M3 nickel-titanium file. The samples were randomly divided into six groups with different sealers and obturation techniques: iRoot SP+single-cone technique (SC), C-Root SP+SC, GFB+SC, iRoot SP+single cone-mediated ultrasonic technique (SU), C-Root SP+SU, and GFB+SU. Samples were scanned by Micro-CT, and the total and segmented filling rates were calculated with Mimics 22.0 software after 3D reconstruction. RESULTS: The overall filling rate of the three biomaterial root canal sealers was higher than 90%. The overall and coronal third and middle third segment filling rate of groups iRoot SP+SC, C-Root SP+SC was higher than that of group GFB+SC (P<0.01), with no significant difference between groups iRoot SP+SC and C-Root SP+SC (P>0.05). On the apical third, no significant difference was found among each group (P>0.05). The overall and segment filling rate of groups iRoot SP+SU and C-Root SP+SU was higher than that of GFB+SU (P<0.01), with no significant difference between groups iRoot SP+SU and C-Root SP+SU (P>0.05). The filling rate of the apical 1/3 of group C-Root+SC was lower than that of group C-Root+SU (P<0.01), and the filling rate of the coronal 1/3 of group GFB+SC was higher than that in the GFB+SU (P<0.01). Nevertheless, no significant difference was found in other filling rate of two obturation techniques (P>0.05). CONCLUSIONS The overall filling rate of the three biomaterial root canal sealers using SC and SU are satisfactory. iRoot SP and C-Root SP have similar filling rates, which are significantly higher than that of GFB. C-Root SP combined with SU technique can improve the filling quality of the root apical.
Root Canal Filling Materials ; X-Ray Microtomography ; Humans ; Root Canal Obturation/methods* ; Gutta-Percha ; Dimethylpolysiloxanes ; Drug Combinations ; Dental Pulp Cavity/diagnostic imaging* ; Bicuspid

OBJECTIVE: To investigate the molecular mechanism and explore blood transfusion strategies for a proband exhibiting the JK (a-b-) phenotype and anti-JK³ high frequency antigen antibody and her eight family members. METHODS: The Kidd blood phenotype and irregular antibodies in a family were identified by serologic tests. Exon 4-11 and intron region of SLC14A1 gene were sequenced by Sanger method. RESULTS: The combination of the gene JK*B (c.499A>G,c.512G>A,c.588A>G) and gene JK*B (c.342-1G>A,588A>G) in this family were considered to result in the JK (a-b-) phenotype in two members. The members carrying gene JK*A(c.130G>A,588A>G) all present serological JK^a+W. Members carrying gene JK*B (c.499A>G,c.588A>G) all present serological JK^b+W, which has not been previously reported to cause antigenic weakening. The proband with JK (a-b-) phenotype produced anti-JK³ antibodies, the hospital formulated a number of blood preparation strategies for the patient and she was discharged after recovery. CONCLUSION In this study, the molecular mechanism of JK (a-b-) in this family was identified, the transfusion strategy of rare blood group was established in our institution preliminary, and the necessity of establishing a rare blood group bank was revealed in this region. It is suggested that JK*B (c.499A>G,c.588A>G) may be a new genetic pattern leading to the weakening of Kidd antigenicity, which lays a foundation for the study of population genetics.
Humans ; Blood Transfusion ; Female ; Kidd Blood-Group System/genetics* ; Phenotype ; Pedigree

The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

Osteoarthritis (OA) is a prevalent degenerative joint disease predominantly affecting the elderly and is characterized by cartilage degradation, synovitis, and subchondral bone sclerosis. Despite its widespread occurrence, no effective pharmacological interventions currently exist to halt or reverse disease progression. Polyphenolic compounds, a diverse class of plant-derived substances, have attracted considerable attention for their potent anti-inflammatory and antioxidant activities. This review summarizes recent advances in understanding the multifaceted roles of polyphenols in OA. Specifically, polyphenols protect chondrocytes and preserve the extracellular matrix by mitigating oxidative stress, suppressing inflammation, regulating autophagy and cholesterol metabolism, and inhibiting programmed cell death pathways, including apoptosis, pyroptosis, and ferroptosis. Furthermore, they exert protective effects on synovial tissue by regulating macrophage polarization and inhibiting pathogenic fibroblast activation, while also contributing to the maintenance of subchondral bone homeostasis. Recent progress in nanotechnology-based delivery systems, designed to overcome the poor solubility and limited bioavailability of polyphenols, is also highlighted. Collectively, this review integrates mechanistic insights with emerging therapeutic strategies, underscoring the potential of polyphenolic compounds as disease-modifying agents for OA.

Breast cancer is the most prevalent malignancy among women worldwide.In recent years,immune checkpoint inhibitors(ICIs)have emerged as a promising therapeutic strategy across different molecular subtypes of breast cancer,demonstrating significant clinical potential.This review systematically summarized the progress and clinical applications of ICIs in hormone receptor-positive(HR-positive),human epidermal growth factor receptor 2-overexpressing(HER2-positive),and triple-negative breast cancer(TNBC).In HR-positive breast cancer,the KEYNOTE-756 and CheckMate 7FL trials demonstrated that ICIs combined with neoadjuvant chemotherapy significantly improved the pathological complete response(pCR)rate,with greater benefits observed in programmed cell death-ligand 1(PD-L1)-positive patients.Furthermore,the PROMENADE study indicated that estrogen receptor(ER)-low HER2-negative breast cancer patients achieved a pCR rate closer to that of TNBC rather than HR-positive breast cancer following ICIs treatment.In metastatic HR-positive breast cancer,the SACI-IO and DOLAF studies suggested that ICIs combined with antibody-drug conjugates(ADC)or poly(ADP-ribose)polymerase(PARP)inhibitors may provide clinical benefits for specific subgroups of patients.For HER2-positive breast cancer,the Keyriched-1 and Neo-PATH studies revealed that ICIs combined with anti-HER2 therapy might improve pCR rates in HR-negative/HER2-positive patients.However,the Impassion-050 and KATE2 trials failed to demonstrate widespread clinical benefits of ICIs in HER2-positive breast cancer.In TNBC,long-term follow-up data from the KEYNOTE-522 study showed that ICIs combined with neoadjuvant chemotherapy not only improved pCR rates but also conferred long-term survival benefits.Additionally,the Impassion-130,KEYNOTE-355,and TORCHLIGHT studies confirmed that ICIs combined with chemotherapy prolonged both progression-free survival(PFS)and overall survival(OS)in PD-L1-positive advanced TNBC patients.Meanwhile,treatment strategies combining ICIs with anti-angiogenic therapy,PARP inhibitors and ADCs have demonstrated promising efficacy in TNBC(SPARK and BEGONIA trial).Currently,ICIs combined with chemotherapy remains the primary treatment approach,while combination strategies involving ICIs with anti-HER2 therapy,endocrine therapy,ADCs,and anti-angiogenic therapy are actively being explored.However,challenges remain,including complex resistance mechanisms,heterogeneous treatment responses,and the management of immune-related adverse events.Future research should focus on refining patient stratification strategies and developing more precise combination therapies to improve long-term survival outcomes for breast cancer patients.

Objective:To analyze the value of 18F-FDG PET/CT combined with MRI in the diagnosis and differential diagnosis of ductal carcinoma in situ (DCIS) and early stage invasive ductal carcinoma (IDC). Methods:From September 2019 to December 2023, 12 patients with DCIS (all females; age 36-67 years) and 34 patients with early stage IDC (all females; age 36-73 years) in Qingdao Central Hospital were retrospectively analyzed. The general clinical information, MRI features, and 18F-FDG PET/CT features of patients were analyzed. χ2 test, Fisher exact test, and Mann-Whitney U test were used to analyze the data. The independent predictors of DCIS were analyzed by logistic regression analysis. The value of different indicators in diagnosing DCIS was analyzed using ROC curves analysis, and Delong test was used to assess the differences among AUCs. Results:The differences in tumor metabolic volume (MTV; 18.55(10.90, 76.30) vs 4.00(2.00, 11.45)cm 3) and total lesion glycolysis (TLG; 44.85(25.30, 125.30) vs 9.40(6.68, 22.35)g) of breast lesion, enhancement pattern (non-mass enhancement (NME); 8/12 vs 29.4%(10/34)), lobulation sign (0/12 vs 58.8%(20/34)), and apparent diffusion coefficient (ADC; 1.33 (1.16, 1.63)×10 -3vs 1.08 (0.75, 1.28)×10 -3mm 2/s) between DCIS and early stage IDC groups were statistically significant ( Z values: from -3.91 to -2.56, χ2=5.17, all P<0.05). When differentiating DCIS from early stage IDC, NME (odds ratio ( OR)=36.50, 95% CI: 2.15-618.52, P=0.013), ADC ( OR=7.85, 95% CI: 1.11-55.46, P=0.044), and TLG ( OR=1.06, 95% CI: 1.02-1.11, P=0.007) were independent predictors. The AUC of the three predictors combination was 0.941, which was higher than those of single predictors ( Z values: 2.00-2.80, P values: 0.005-0.046). Conclusion:The combination of 18F-FDG PET/CT and MRI improves the efficacy of differential diagnosis between DCIS and early stage IDC, thereby providing a basis for developing personalized treatment plans for patients.