Flavonoids, the key active compounds in Epimedii Folium, have both protective and toxic effects on the liver. Their hepatoprotective effects are associated with reducing lipid accumulation and oxidative stress, which contribute to the management of various liver conditions. In contrast, the mechanisms driving Epimedii Folium-induced hepatotoxicity are less understood but likely involve oxidative stress and pyroptosis. Pharmacokinetic studies, especially on icaritin, indicate that it undergoes isopentenyl dehydrogenation, glycosylation, and glucuronidation in vivo, contributing to its pharmacological effects. However, intermediate metabolites of icaritin may interact with biomolecules, potentially leading to liver toxicity. This review offers a detailed examination of the dual effects of Epimedii Folium flavonoids on liver function, emphasizing recent discoveries in their hepatoprotective and hepatotoxic pathways. We also summarize and discuss the pharmacokinetics of these flavonoids, highlighting how their metabolism affects therapeutic efficacy and toxicity. Lastly, we propose strategies to mitigate liver injury, providing new perspectives on the safe use of Epimedii Folium.

Objective:To investigate the effects of Wnt5a on the vasculogenic mimicry(VM)and cancer stem cell(CSC)properties of prostate cancer(PCa)cells by upregulating the expression of miR-141-3p.Methods:Human prostate epithelial cell line RWPE-1 and PCa cell lines PC-3,LNCaP,and DU145 were cultured.qPCR was employed to detect miR-141-3p expression,and Western blotting(WB)was used to measure Wnt5a protein levels.Stable Wnt5a-knockdown or miR-141-3p-knockdown LNCaP and DU145 cell lines were established respectively via plasmid transfection.VM formation ability was assessed by three-dimensional culture assay.Cell proliferation ability and drug sensitivity were measured by CCK-8 assay.Cell migration and invasion abilities were detected using wound healing and Transwell assays,respectively.The expressions of VM-related molecules and CSC markers were detected by qPCR and WB.Colony formation ability was determined by clonogenic assay.The proportion of CD133+cells was sorted and calculated by flow cytometry.The expressions of miR-141-3p and Wnt5a in CD133+and CD133-cells were detected by qPCR and WB.Stable Wnt5a-overexpressing PCa cell lines were constructed via plasmid transfection.The effects of Wnt5a and different Wnt pathway downstream inhibitors on miR-141-3p expression and promoter activity were detected by qPCR and dual-luciferase reporter assays.Expression of c-Jun was knocked down in Wnt5a-overexpressing cells using si-c-Jun transfection.The target binding relationship between c-Jun and the miR-141-3p promoter was verified by qPCR,dual-luciferase reporter assay,and chromatin immunoprecipitation assay.Results:The expressions of miR-141-3p and Wnt5a were significantly higher in PCa cells compared with those in RWPE-1 cells,with the highest relative expression in DU145 cells and the lowest in LNCaP cells(P<0.001).Downregulation of Wnt5a or miR-141-3p significantly inhibited VM formation ability and stemness of PCa cells,and significantly suppressed the proliferation,migration,invasion abilities,and enhanced the sensitivity to bicalutamide of PCa cells(P<0.05 or P<0.01 or P<0.001).Downregulation of Wnt5a significantly inhibited miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.05),whereas upregulation of Wnt5a significantly promoted miR-141-3p expression and promoter transcriptional activity(P<0.01 or P<0.001).The promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity could be inhibited by a JNK/c-Jun pathway inhibitor(P>0.05).Downregulation of c-Jun significantly inhibited the promoting effect of Wnt5a on miR-141-3p expression and promoter transcriptional activity(P>0.05).c-Jun could bind to the-348 to-295 sequence of the miR-141-3p promoter.In absence of this fragment Wnt5a wouldn't promote miR-141-3p expression(P>0.05).Conclusion:The Wnt5a/JNK/c-Jun signaling pathway can upregulate miR-141-3p expression,and thereby promote VM formation in PCa cells,possibly by activating CSC properties.

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.

Objective:To evaluate the effects of different intervention measures on duration of mechanical ventilation and the length of intensive care unit (ICU) stay in critically ill patients using network Meta-analysis.Methods:Randomized controlled trial (RCT) on the effects of different intervention measures on duration of mechanical ventilation and the length of ICU stay in critically ill patients were systematically searched in PubMed, Embase, China Biomedical Literature Database, CNKI, and other databases. The search time limit was from the establishment of the database to November 2023. Literature screening, quality assessment, and data extraction were independently conducted by two researchers. Network Meta-analysis was employed to assess the effects of each intervention on duration of mechanical ventilation and the length of ICU stay, and funnel plots were generated.Results:A total of 37 RCTs were included, involving 3?977 severe patients, 2?041 in the intervention group and 1?936 in the control group. Thirteen types of interventions were analyzed, including usual care (UC), early activity (EA), early comprehensive rehabilitation (ECR), early pulmonary rehabilitation (EPR), cluster intervention strategy (CS), sedation, analgesia and cluster nursing (SACN), music therapy (MT), neuromuscular electrical stimulation (NMES), modified education and visitation (MV), virtual reality (VR), auricular point sticking (APS), acupoint acupuncture (AA), and concerted intervention (COR). Network Meta-analysis showed that MV significantly better than COR [standardized mean difference ( SMD) = -2.35, 95% confidence interval (95% CI) was -4.30 to -0.39], EPR ( SMD = -2.59, 95% CI was -4.81 to -0.37), and UC ( SMD = -4.10, 95% CI was -5.71 to -2.49) in improving duration of mechanical ventilation in critically ill patients. COR was significantly better than UC in shortened length of ICU stay ( SMD = -5.72, 95% CI was -10.07 to -1.37). The efficacy ranking results showed that for duration of mechanical ventilation, the surface under the cumulative ranking curve (SUCRA) was highest for MV (85.4%) and EA (85.4%), followed by AA (74.9%), NMES (63.1%), ECR (51.7%), CS (48.8%), SACN (34.3%), COR (29.4%), EPR (26.1%), and UC (0.7%). For the length of ICU stay, COR had the highest SUCRA (82.3%), followed by APS (79.7%), MV (77.7%), EPR (68.0%), NMES (57.6%), CS (54.4%), ECR (51.1%), SACN (41.9%), MT (39.8%), EA (39.3%), AA (33.0%), VR (15.4%), and UC (9.8%). The funnel plot results of ICU stay showed that the publication bias between studies were relatively small. Conclusions:MV and COR appear to be effective interventions for reducing mechanical ventilation time and ICU stay in critically ill patients. However, due to the number and quality of included studies, these findings require confirmation through additional high-quality research.

Purpose To observe the changes in the brain microstructure of children with global developmental delay(GDD)via MR diffusion kurtosis imaging(DKI).Materials and Methods A total of 34 children with GDD were included as the experimental group,and 34 children with normal development as the control group in the Third Affiliated Hospital of Zhengzhou University from September 2020 to March 2023,retrospectively.DKI and clinical data were collected.After post-processing,DKI parameters were obtained,including fraction anisotropy,mean kurtosis(MK),axial kurtosis and radial kurtosis(Kr).The differences in parameters in each region of interest of the two groups were analyzed,the correlation between DKI parameters and Gesell developmental scale was analyzed,and the receiver operating characteristic curve was drawn to analyze the diagnostic efficacy of DKI parameters.Results Compared with the control group,the MK value of the centrum semiovale decreased(Z=-2.723,P<0.01),the MK value and Kr value of the thalamus decreased(t/Z=-3.220,-3.128,both P<0.01),the MK value and axial kurtosis value of the anterior and posterior limb of internal capsule decreased(t/Z=-2.958,-2.573,-2.085,-2.403,all P<0.05),the Kr value of the anterior limb of internal capsule decreased(t=-2.155,P<0.05),the MK value and Kr value of frontal white matter decreased(Z=-2.177,-2.711,both P<0.05).The correlation analysis showed that the MK and Kr value of the anterior limb of the internal capsule and the MK value of the posterior limb of the internal capsule were positively correlated with the score of the gross motor functional area(r=0.379,0.378,0.405,all P<0.05),and the MK value of the posterior limb of the internal capsule was positively correlated with the fine motor functional area(r=0.461,P=0.006).The Kr value of the thalamus had the largest area under the curve at 0.721 when diagnosing GDD.Conclusion Children with GDD have changes in brain microstructure,and DKI has a certain value for diagnosis.

Background: Peste des petits ruminants (PPR), caused by the PPR virus (PPRV), is an acute and fatal contagious disease that mainly infects goats, sheep, and other artiodactyls.Peripheral blood mononuclear cells (PBMCs) are considered the primary innate immune cells. Objectives: PBMCs derived from goats were infected with PPRV and analyzed to detect the relationship between PPRV replication and apoptosis or the inflammatory response. Methods: Quantitative real-time polymerase chain reaction was used to identify PPRV replication and cytokines expression. Flow cytometry was conducted to detect apoptosis and the differentiation of CD4+ and CD8+T cells after PPRV infection. Results: PPRV stimulated the differentiation of CD4+ and CD8+ T cells. In addition, PPRV induced apoptosis in goat PBMCs. Furthermore, apoptosis and the inflammatory response induced by PPRV could be suppressed by Z-VAD-FMK and Z-YVAD-FMK, respectively.Moreover, the virus titer of PPRV was attenuated by inhibiting caspase-1-dependent apoptosis and inflammation. Conclusions This study showed that apoptosis and the inflammatory response play an essential role in PPR viral replication in vitro, providing a new mechanism related to the cell host response.

Objective Health education resource allocation is one of the basic indicators for evaluating health equity. At present, the research on the equity of health education resource allocation in China is mostly limited to a single year or regional data. This study was aimed to understand the equity of health education resources in the whole China from 2015-2019, and to provide a corresponding basis for further rational allocation of health education resources. Methods The data was obtained based on the number of health education training work, health education publicity work, distribution of health education publicity materials and the annual use of funds carried out mainly by the CDC or health education centers in each province according to the 2016-2020 China Health Statistics Yearbook. The inequality coefficient (Gini coefficient) and Lorenz curve were applied to study the selected data. Results The total number of health education resources in China from 2015-2019 was 1 789 735 and 1 933 336, respectively. The Gini coefficients of health education resource allocation by population distribution were all below the warning line of 0.4, which were in an equitable state. Conclusion The equity of health education resources in China is good according to demographic indicators, and there is no significant inequity. Especially, the aspects of health education services, such as technical consultation and media cooperation, are relatively good, but there is still much room for improvement in the construction of websites.

Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.

Cutaneous hemangioma is a kind of benign skin vascular tumor caused by congenital abnormal vascular development. The rays emitted by 90Sr has a good effect on it. Meanwhile, 90Sr application is easy to operate, effective, with less side effects and painless. It is a method worthy of promotion in the treatment of skin hemangioma. This article reviews the application of 90Sr application in cutaneous hemangioma treatment.

Objective:To investigate the clinical effect of 90Sr application on superficial hemangioma in hair area and its effect on the volume of hair. Methods:A total of 136 pediatric patients (55 males, 81 females, 1-30 months old; 136 lesions) with head hemangioma in the First Affiliated Hospital of Guangxi Medical University between February 2018 and October 2019 were enrolled. They were divided into 3 groups according to the hair density of tumor sites. Group A ( n=63, 3(2, 6) months old, male/female=27/36): the hair in tumor sites was as thick as the surrounding hair. Group B ( n=40, 3(2, 5) months old, male/female=17/23): the hair in tumor sites was thinner than the surrounding area. Group C ( n=33, 3(2, 6) months old, male/female=11/22): there was no hair growth in the tumor sites. All groups were treated with 90Sr application, and the total absorbed dose of each course was 10-30 Gy, which was divided into 8 times. Three to four months after the treatment, the efficacy and adverse reactions were evaluated and the volume of hair was divided into 3 grades according to the hair density of the tumor sites: flourishing, good growth and no growth. If the clinical effect was unsatisfied, a second course of treatment was conducted. Kruskal-Wallis rank sum test or χ 2 test was used for data analysis. Results:The differences of age ( H=0.01), gender ( χ 2=0.92) among group A, group B and group C were not significant (both P>0.05). The total recovery rates of 3 groups after two-course treatment were 88.9%(56/63), 95.0%(38/40) and 93.9%(31/33) respectively ( χ 2=1.49, P>0.05). Besides, the incidences of adverse reactions were 6.3%(4/63), 7.5%(3/40) and 9.1%(3/33) respectively ( χ 2=0.24, P>0.05). Three to four months after treatment, the hair on tumor sites in group A and B was rated as flourishing, 28 children in group C were rated as flourishing, 5 children were rated as good growth, and none of the children showed no growth. Conclusions:The 90Sr application has a good treatment effect on the small superficial hemangioma in the hair area of infants, and the amount of hair in the affected area can be restored to normal after treatment. This treatment is worthy of clinical application.