ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

Erectile Dysfunction(ED)is a relatively common clinical condition characterized by male sexual dysfunction.Macrophages,as key components of the immune and inflammatory response systems,play crucial roles in immune surveillance,tissue repair,and the maintenance of tissue homeostasis in processes related to erectile function.Immune inflammation is recognized as one of the pathological factors contributing to ED,and inflammatory markers—including macrophages—are widely believed to be closely associated with the onset of the disorder.This review summarizes the multifaceted roles of macrophages in vascular injury,neural repair,hormonal balance,and immune microenvironment remodeling in the context of erection.It aims to provide a theoretical foundation for further investigation into the involvement of macrophages in ED and discusses the potential of macrophage-targeted therapies for treating ED.

Objective To investigate the expression of retinoblastoma-binding protein 7(RBBP7)in esophageal cancer and its molecular mechanism affecting its progression.Methods The tumor specimens and corresponding adjacent normal tissue specimens of 65 patients with esophageal cancer undergoing radical resection in the General Hospital of Wanbei Coal and Electricity Group Affiliated to Bengbu Medical University from January 2018 to December 2019 were collected.The expression of RBBP7 in esophageal cancer tissues was detected by immunohistochemistry,and the clinical correlation was analyzed.Eca109 and Kyse510 esophageal cancer cell lines were selected to detect the expression of RBBP7 in esophageal cancer cells by Western blot.The experiments were divided into Vector group,RBBP7 group,NC group and si-RBBP7 group by transfection technology.CCK-8 assay,colony formation assay,Transwell assay,wound healing assay and Western blot were used to detect the effect of RBBP7 on the proliferation,invasion,migration and radioresistance of esophageal cancer cells and its mechanism.Results The results of immunohistochemistry in clinical samples and Western blot in esophageal cancer cell lines showed that RBBP7 was highly expressed in esophageal cancer tissues compared with normal adjacent tissues(P<0.05),and esophageal cancer patients with high expression of RBBP7 had a poor prognosis(P<0.05).In the mechanism study,we found that overexpression of RBBP7 promoted the proliferation of esophageal cancer cells by CCK-8 and colony formation assay in vitro(P<0.05).Overexpression of RBBP7 promoted the invasion,migration,and radioresistance of esophageal cancer cells(P<0.05),and vice versa inhibited the proliferation,invasion,migration,and radioresistance of esophageal cancer cells(P<0.05).The results of Western blot showed that compared with the Vector control group,overexpression of RBBP7 may regulate the malignant progression and radioresistance of esophageal cancer by activating Hippo signaling pathway(P<0.05).Conclusion RBBP7 promotes the development and radioresistance of esophageal cancer through Hippo signaling pathway

Erectile Dysfunction(ED)is a relatively common clinical condition characterized by male sexual dysfunction.Macrophages,as key components of the immune and inflammatory response systems,play crucial roles in immune surveillance,tissue repair,and the maintenance of tissue homeostasis in processes related to erectile function.Immune inflammation is recognized as one of the pathological factors contributing to ED,and inflammatory markers—including macrophages—are widely believed to be closely associated with the onset of the disorder.This review summarizes the multifaceted roles of macrophages in vascular injury,neural repair,hormonal balance,and immune microenvironment remodeling in the context of erection.It aims to provide a theoretical foundation for further investigation into the involvement of macrophages in ED and discusses the potential of macrophage-targeted therapies for treating ED.

Objective To compare the effects of single antiplatelet therapy(SAPT)versus dual antiplatelet therapy(DAPT)on bleeding and ischemic events in patients undergoing transcatheter aortic valve replacement(TAVR)without long-term anticoagulation indications.Methods This randomized controlled trial included 90 post-TAVR patients without anticoagulation indications,who were allocated to the SAPT group(n=46,aspirin 100 mg/d)or DAPT group(n=44,aspirin 100 mg/d+clopidogrel 75 mg/d for 3 months,followed by aspirin monotherapy).Maximum aggregation rates of platelets induced by arachidonic acid(MARAA)and adenosine diphosphate(MARADP)were measured 1,3,6,and 12 months postoperatively.Bleeding and ischemic events were recorded during the follow-up visits.Results The SAPT group exhibited significantly higher MARAA and MARADP scores at 1 and 3 months,and higher MARAA scores at 6 months compared to the DAPT group(P<0.05).At the 12-month follow-up,the SAPT group had a significantly lower inci-dence of bleeding events compared to the DAPT group(13.0%vs.31.8%,P=0.043).No statistically significant difference was observed in ischemic events between the groups(15.2%vs.11.4%,P=0.759).Conclusion For TAVR patients without anticoagulation indica-tions,SAPT significantly reduced the 1-year bleeding risk compared to DAPT,without increasing ischemic events.These findings support the safety and efficacy of SAPT after TAVR.

Anatomy of laboratory animals plays an important role in laboratory animal science,veterinary medicine,and other life sciences.Integrating mind mapping into the entire teaching process can effectively help teachers to optimize the organization of teaching contents and stimulate students' enthusiasm and self-motivation for learning.This manuscript aims to explore the feasibility,advantages,and challenges of applying mind-mapping tools for teaching anatomy of laboratory animals.We analyze the different application scenarios from the perspectives of both teachers and students,with the aim of providing practical teaching tools and methodologies to enhance instructional effectiveness in the teaching of anatomy of laboratory animals.

Objective To compare the effects of single antiplatelet therapy(SAPT)versus dual antiplatelet therapy(DAPT)on bleeding and ischemic events in patients undergoing transcatheter aortic valve replacement(TAVR)without long-term anticoagulation indications.Methods This randomized controlled trial included 90 post-TAVR patients without anticoagulation indications,who were allocated to the SAPT group(n=46,aspirin 100 mg/d)or DAPT group(n=44,aspirin 100 mg/d+clopidogrel 75 mg/d for 3 months,followed by aspirin monotherapy).Maximum aggregation rates of platelets induced by arachidonic acid(MARAA)and adenosine diphosphate(MARADP)were measured 1,3,6,and 12 months postoperatively.Bleeding and ischemic events were recorded during the follow-up visits.Results The SAPT group exhibited significantly higher MARAA and MARADP scores at 1 and 3 months,and higher MARAA scores at 6 months compared to the DAPT group(P<0.05).At the 12-month follow-up,the SAPT group had a significantly lower inci-dence of bleeding events compared to the DAPT group(13.0%vs.31.8%,P=0.043).No statistically significant difference was observed in ischemic events between the groups(15.2%vs.11.4%,P=0.759).Conclusion For TAVR patients without anticoagulation indica-tions,SAPT significantly reduced the 1-year bleeding risk compared to DAPT,without increasing ischemic events.These findings support the safety and efficacy of SAPT after TAVR.

Anatomy of laboratory animals plays an important role in laboratory animal science,veterinary medicine,and other life sciences.Integrating mind mapping into the entire teaching process can effectively help teachers to optimize the organization of teaching contents and stimulate students' enthusiasm and self-motivation for learning.This manuscript aims to explore the feasibility,advantages,and challenges of applying mind-mapping tools for teaching anatomy of laboratory animals.We analyze the different application scenarios from the perspectives of both teachers and students,with the aim of providing practical teaching tools and methodologies to enhance instructional effectiveness in the teaching of anatomy of laboratory animals.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.