Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

: To explore the relationship between metal exposure level and blood pressure, so as to provide a scientific basis for verifying the relationship between metal exposure and elevated blood pressure among primary school students. Methods: In July 2022, a total of 555 students of second to sixth grade were selected by cluster random sampling method from two primary schools in Zhuxi County, Shiyan City, Hubei Province. A questionnaire survey was conducted to obtain the socio demographic characteristics and living habits of the participants. The height, weight, body mass index(BMI) and blood pressure were obtained by physical examination. At the same time, the urine of the subjects was collected, and the metal mass fraction in urine was detected by inductively coupled plasma mass spectrometry. The relationship between metal mass fraction in urine and blood pressure was analyzed by generalized linear regression. Results: The detection rate of elevated blood pressure in primary school students was 15.86% , and there was a statistically significant difference in the detection rate of elevated blood pressure among obese primary school students (yes:37.25%,no:13.69%, χ 2=19.28, P <0.01).There were statistically significant differences in BMI[15.80( 14.69 ， 17.92 )，17.87(15.49，20.89)kg/m 2] between the non elevated blood pressure group and the elevated blood pressure group of elementary school students ( Z =-4.67, P <0.01). The geometric mean mass fraction of zinc in urine was the highest ( 6 942.86 μg/g), titanium was the lowest (2.20 μg/g). Zinc and lead were positively correlated with elevated systolic blood pressure( β = 0.054 , 0.014), zinc and cadmium were positively correlated with elevated diastolic blood pressure ( β =0.038,0.029) ( P <0.05). Conclusions Metal zinc, lead and cadmium concentration are associated with elevated blood pressure. It is necessary to intervene and control the exposure of zinc, lead and cadmium in the environment to promote the blood pressure health of primary school students.

Objective To assess the influence of inter-implant distances on the accuracy of intraoral scanning im-pressions in vitro.Methods A master cast model with different inter-implant distances was scanned by laboratory and intraoral scanners,which were used as the reference and intraoral scan data.The distance and angular devia-tions of the scan bodies corresponding to the reference and intraoral digital scan standard tessellation language(STL)files were measured and calculated in a three-dimensional analysis software.The one-sample t-test,Spearman's correlation analysis,Brown-Forsythe F test,Games-Howell post-hoc test,and Levene's test were used for comparisons(α=0.05).Results The overall distance and angular deviations of the intraoral digital scan were(27.48±18.14)μm and(0.24±0.19)°,within clinically acceptable limits(P＜0.001).The inter-implant distances exhibited a significant positive correlation with both the scanning distance and angular deviations in terms of scanning trueness.The angular deviation differed significantly between the 1-2 group(8.13 mm)and the other distance groups.Additionally,inter-implant distances affected the precision of the intraoral scanner(P＜0.05).Conclusion The findings of this study indicate that intraoral scanning impressions of complete-arch implant-sup-ported prostheses are within clinically acceptable ranges of accuracy.Inter-implant distances≤8.13 mm can result in a higher accuracy of intraoral scanning.Increased inter-implant distances can adversely affect intraoral scanning accuracy.

Objective To uncover and identify the differences in salivary microbiota profiles and their potential roles between patients with pulmonary nodules(PN)and healthy controls,and to propose new candidate biomarkers for the early warning of PN.Methods 16S rRNA amplicon sequencing was performed with the saliva samples of 173 PN patients,or the PN group,and 40 health controls,or the HC group,to compare the characteristics,including diversity,community composition,differential species,and functional changes of salivary microbiota in the two groups.Random forest algorithm was used to identify salivary microbial markers of PN and their predictive value for PN was assessed by area under the curve(AUC).Finally,the biological functions and potential mechanisms of differentially-expressed genes in saliva samples were preliminarily investigated on the basis of predictive functional profiling of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt2).Results The α diversity and βdiversity of salivary microbiota in the PN group were higher than those in the HC group(P＜0.05).Furthermore,there were significant differences in the community composition and the abundance of oral microorganisms between the PN and the HC groups(P＜0.05).Random forest algorithm was applied to identify differential microbial species.Porphyromonas,Haemophilus,and Fusobacterium constituted the optimal marker sets(AUC=0.79,95％confidence interval:0.71-0.86),which can be used to effectively identify patients with PN.Bioinformatics analysis of the differentially-expressed genes revealed that patients with PN showed significant enrichment in protein/molecular functions involved in immune deficiency and redox homeostasis.Conclusion Changes in salivary microbiota are closely associated with PN and may induce the development of PN or malignant transformation of PN,which indicates the potential of salivary microbiota to be used as a new non-invasive humoral marker for the early diagnosis of PN.

Abernethy malformation， also known as congenital portosystemic shunts， is rare in clinical practice， with less than 300 cases reported in the global literature up to 2019. The disease can have serious complications such as pulmonary hypertension， liver tumor， and liver failure and tends to have an extremely poor prognosis， and early diagnosis and active and effective treatment can reduce and delay the onset of complications. In this case， portography combined with balloon occlusion helped to display the underdeveloped slender portal vein with dysplasia， so that the child who was formerly misdiagnosed with type Ⅰ Abernethy malformation was diagnosed with type Ⅱ Abernethy malformation， and then the child was successfully treated by transcatheter closure. This article gives a detailed report of this case.

Pyroptosis， an atypical new cell death mode other than apoptosis and necrosis， has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins （GSDMs） by Caspases. The activated GSDMs act on the plasma membrane to form a perforation， which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways， including canonical and non-canonical inflammasome pathways， apoptosis-associated Caspases-mediated pathway， and granzyme pathway. In these signaling pathways， GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect， and meanwhile stimulate the tumor immune microenvironment， while it can promote tumor development. Despite the good performance， drug-based anti-tumor therapies such as tumor immunotherapy， chemotherapy， and targeted therapy have some shortcomings such as drug resistance， recurrence， and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner， which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment， and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy， with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.

OBJECTIVE To establish a total quality management system for pharmacy intravenous admixture services （PIVAS）， in order to promote the standardization， accuracy and rationalization of clinical intravenous infusion. METHODS Based on information system in PIVAS， the management system and quality monitoring items of the whole process before， during and after PIVAS infusion preparation were formulated. The quality control and quality improvement were carried out regularly with quality management tools and methods such as PDCA （plan， do， check， process） cycle， quality control circle， and root cause analysis. The main quality control indexes of PIVAS were retrospectively analyzed before （in 2019） and after PDCA cycle management （in 2020 and 2021）. RESULTS The indexes of quality monitoring in the whole process of PIVAS infusion preparation， such as the score of drug quality management， the drug residue qualification rate and the qualified rate of drug content in infusion， were increased from 92 points， 79%， 86.4% in 2019 to 99 points， 92%， 99.8% in 2021， respectively. The indexes of safe and rational drug use， such as the ratio of intravenous irrational medical orders， the rate of drug repercussion， the rate of antibiotics use， and the rate of TCM injection use decreased from 0.98%， 6.1%， 40.55%， 39.70% to 0.23%， 3.2%， 37.18%， 26.00%， respectively. CONCLUSIONS The established total quality management system for PIVAS can improve the quality management level in the infusion preparation process， improve the quality of infusion preparation and promote clinical safe and rational drug use.

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Pyroptosis ; Caspase 3/metabolism* ; Network Pharmacology ; Gasdermins ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism*