Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

AIM: To explore the diagnostic value of 18 MHz color Doppler ultrasonography for epiretinal membrane.METHODS: A total of 44 cases(80 eyes)of patients with proposed diagnosis of cataract and vitreous opacity by fundus examination in our hospital between January 2020 and January 2022 were collected, and the affected eyes were examined by optical coherence tomography(OCT)and 18 MHz color Doppler ultrasonography, and the differences in the diagnostic sensitivity, specificity, and accuracy were compared between 18 MHz color Doppler ultrasonography and OCT for the diagnosis of epiretinal membrane.RESULTS: In the 80 eyes detected by 18 MHz color Doppler ultrasonography, 62 had epiretinal membrane and 18 had non epiretinal membrane. Totally 54 eyes were confirmed to have epiretinal membrane by OCT, 13 eyes were not diagnosed with epiretinal membrane, 5 eyes were missed diagnosis, and 8 eyes were misdiagnosed. The diagnostic consistency between 18 MHz color Doppler ultrasonography and OCT was high(Kappa=0.892, P<0.05); the 18 MHz color Doppler ultrasonography detection sensitivity of epiretinal membrane was 92%, specificity was 62%, missed diagnosis rate was 8%, misdiagnosis rate was 38%, and accuracy was 84%; compared with OCT detection, 18 MHz color Doppler ultrasonography detected a lower specificity, correct rate, positive prediction accuracy, negative prediction accuracy, and higher misdiagnosis rate(all P<0.05), and the difference in diagnostic sensitivity compared with leakage rate was not statistically significant(all P>0.05).CONCLUSION: 18 MHz color Doppler ultrasonography has some value in identifying epiretinal membrane lesions and is consistent with OCT testing.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China

OBJECTIVES: To investigate the clinical sub-phenotype (SP) of pediatric acute kidney injury (AKI) and their association with clinical outcomes. METHODS: General status and initial values of laboratory markers within 24 hours after admission to the pediatric intensive care unit (PICU) were recorded for children with AKI in the derivation cohort (n=650) and the validation cohort (n=177). In the derivation cohort, a least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify death-related indicators, and a two-step cluster analysis was employed to obtain the clinical SP of AKI. A logistic regression analysis was used to develop a parsimonious classifier model with simplified metrics, and the area under the curve (AUC) was used to assess the value of this model. This model was then applied to the validation cohort and the combined derivation and validation cohort. The association between SPs and clinical outcomes was analyzed with all children with AKI as subjects. RESULTS: In the derivation cohort, two clinical SPs of AKI (SP1 and SP2) were identified by the two-step cluster analysis using the 20 variables screened by LASSO regression, namely SP_d1 group (n=536) and SP_d2 group (n=114). The simplified classifier model containing eight variables (P<0.05) had an AUC of 0.965 in identifying the two clinical SPs of AKI (P<0.001). The validation cohort was clustered into SP_v1 group (n=156) and SP_v2 group (n=21), and the combined derivation and validation cohort was clustered into SP1 group (n=694) and SP2 group (n=133). After adjustment for confounding factors, compared with the SP1 group, the SP2 group had significantly higher incidence rates of multiple organ dysfunction syndrome and death during the PICU stay (P<0.001), and SP2 was significantly associated with the risk of death within 28 days after admission to the PICU (P<0.001). CONCLUSIONS This study establishes a parsimonious classifier model and identifies two clinical SPs of AKI with different clinical features and outcomes.The SP2 group has more severe disease and worse clinical prognosis.
Humans ; Acute Kidney Injury/diagnosis* ; Prognosis ; Male ; Female ; Child ; Child, Preschool ; Phenotype ; Infant ; Logistic Models ; Adolescent

OBJECTIVE: To analyze the correlation between baseline ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and circulating tumor DNA (ctDNA) parameters in diffuse large B-cell lymphoma (DLBCL) and compare the value of the two methods in the prognosis assessment of DLBCL. METHODS: A total of 50 DLBCL patients confirmed by pathology, including 26 males and 24 females, with a median age of 55.5(43.5, 64.0) years from August 2018 to April 2021 were retrospectively analyzed. PET/CT parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), ctDNA parameters, including mutation number, mutation gene number, mean variant allele frequency (meanVAF), and clinical data of patients were collected. The relationship between PET/CT, ctDNA parameters and patient clinical features was analyzed, as well as the correlation between PET/CT and ctDNA parameters. The diagnostic efficacy of PET/CT and ctDNA parameters was compared. Patients were followed up for 36-69 months. Progression-free survival (PFS) was calculated, and survival analysis was performed. RESULTS: PET/CT parameters all had good correlation with ctDNA parameters, among which MTV was moderately correlated with mutation number, mutation gene number, and meanVAF (r_s=0.72, 0.64, 0.71), TLG was strongly correlated with mutation number (r_s=0.83) and moderately correlated with mutation gene number and mean VAF (r_s=0.72, 0.79), while SUVmax was weakly correlated with mutation number, mutation gene number and meanVAF (r_s=0.47, 0.46, 0.47). PET/CT parameters and ctDNA parameters showed no statistically significant differences in predicting the prognosis of DLBCL and area under the curve (AUC) of receiver operating characteristic (ROC) (P >0.05). However, the specificity of MTV and TLG in predicting prognosis of 1-, 2- and 3-year PFS was better than that of meanVAF (all P < 0.05), while the sensitivity of meanVAF in predicting prognosis of 1-, 2- and 3-year PFS was better than that of MTV (all P < 0.05). The optimal cut-off values of SUVmax, MTV, TLG, mutation number, mutation gene number and meanVAF in predicting tumor progression were obtained using ROC curve analysis. Patients were divided into high and low expression groups according to the cut-off values and survival analysis was performed. The results of survival analysis showed that there were statistically significant differences in PFS between the high and low expression groups (all P < 0.05). CONCLUSION Baseline ¹⁸F-FDG PET/CT and ctDNA parameters can both predict the prognosis of DLBCL, and are equally valuable in the evaluation of DLBCL prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Middle Aged ; Prognosis ; Female ; Male ; Circulating Tumor DNA ; Retrospective Studies ; Adult ; Mutation

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds.Search Genecards,OMIM,Drugbank,TTD,and PharmGKB databases to obtain targets for gastric cancer.The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer.The String database was utilized construct a protein-protein interaction(PPI)network.Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the shared targets.This process revealed significant regulatory pathways crucial for jolkinolide B's efficacy in treating gastric cancer.Cytoscape 3.7.1 software was utilized create the core network of"Potential Targets of Triptolide B in Gastric Cancer Treatment",and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.Results Jolkinolide B may target multiple proteins,including MAPK1,glycogen synthase kinae-3β(GSK-3β),and JUN,impacting the proliferation,invasion,and metastasis of gastric cancer,ultimately inhibiting its growth.Conclusion We predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Objective To explore the mechanism of cinobufagin(CBG)in treating gastric cancer based on network pharmacology combined with bioinformatics and molecular docking technology.Methods Active ingredients and potential targets of CBG in treating gastric cancer were collected from PubChem,TCMSP,and SwissTargetPrediction databases.Transcriptional data of gastric cancer samples were obtained from TGGA database,and gastric cancer-related targets were identified through differential gene analysis.Intersection of targets between CBG and gastric cancer diseases was subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Protein-protein interaction(PPI)network of common targets was constructed using STRING database,and core targets were selected using Cytoscape software.Molecular docking verification of core targets screened with SYBYL-X 2.1.1 software was conducted with CBG.Results CBG treatment of gastric cancer involved 59 targets,with 19 key targets identified.Key targets such as aurora kinase A(AURKA),cyclin-dependent kinase 1(CDK1),enhancer of zeste homolog 2(EZH2),hepatocyte growth factor receptor(MET),matrix metallopeptidase 3(MMP-3),progesterone receptor(PGR),prostaglandin-endoperoxide synthase 1(PTGS1),and thymidylate synthase(TYMS)which exhibited good binding activity with CBG and were closely associated with gastric cancer prognosis.Conclusion CBG may exert anti-gastric cancer effects through multiple targets and pathways.