Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P＜0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P＜0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.