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.

BACKGROUND:Titanium and its alloys are widely used in orthopedic implants due to their excellent biocompatibility,corrosion resistance,and mechanical properties.However,it has biological inertia itself,cannot provide a good growth environment for osteoblasts,and it is difficult to form good osseointegration. OBJECTIVE:To construct a composite hydrogel material of gelatin methacryloyl and polyacrylamide on the surface of titanium alloy scaffold,and analyze its osteogenic ability in vitro. METHODS:Gelatin methacryloyl was mixed with acrylamide.Crosslinking agent and catalyst were added to synthesize gelatin methacryloyl and acrylamide(Gelma-PAAM)composite hydrogel.The titanium alloy scaffold modified by affinity silane was mixed with the Gelma hydrogel and Gelma-PAAM composite hydrogel to complete the loading(recorded as Ti-Gelma and Ti-Gelma-PAAM,respectively).The swelling ratio and degradation rate of the two hydrogels on the surface of the scaffold were compared.The bonding state between hydrogels and titanium alloy was observed by scanning electron microscope.Rat bone marrow mesenchymal stem cells were inoculated into Ti,Ti-Gelma and Ti-Gelma-PAAM scaffolds,separately.Cell proliferation,adhesion,and osteogenic differentiation were detected. RESULTS AND CONCLUSION:(1)Compared with Gelma hydrogel,Gelma-PAAM hydrogel had higher swelling rate and lower degradation rate.(2)Scanning electron microscope showed that the surface of the two kinds of hydrogels was honeycomb structure.After being combined with porous titanium alloy scaffold,the film was wrapped on the surface of scaffold and filled with pores.Among them,the Gelma-PAAM composite hydrogel coated the scaffold more fully.(3)CCK-8 assay and live/dead fluorescence staining showed that bone marrow mesenchymal stem cells proliferated well after coculture with Ti-Gelma and Ti-Gelma-PAAM scaffolds and maintained high activity.After osteogenic induction culture,alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of titanium alloy scaffold group were the lowest,and alkaline phosphatase activity,calcium deposition,and osteogenic gene expression of cells of Ti-Gelma-PAAM scaffold group were the highest.(4)Phalloidin cytoskeletal staining exhibited that the cells of pure titanium alloy scaffold group and Ti-Gelma scaffold group were sparse and insufficiently extended,while the cells of Ti-Gelatin-PAAM group had the most adequate stretching and the densest filamentous actin.(5)The results show that Gelma-PAAM hydrogel has good biocompatibility and osteogenic ability,and is more suitable for osteogenic modification on the surface of titanium alloy than Gelma hydrogel.

OBJECTIVE To explore the effects of multi-disciplinary comprehensive management team of tertiary hospital collaborated with the pharmacists from community health service center （hereinafter referred to as “community pharmacists”） on elderly patients with hypertension in the community. METHODS Elderly patients with hypertension from May 2020 to May 2021 in Yuhua Community Health Service Center of Nanjing were divided into control group （76 cases） and observation group （76 cases） according to the management style. The control group was treated with regular community medical services and the observation group received regular community medical services plus pharmaceutical care provided by the comprehensive management team collaborated with community pharmacists. The compliance， blood pressure control status and hypertension-related complications were compared between 2 groups before management and after 24 months of management. RESULTS After 24 months of management， the compliance and blood pressure compliance rates in both groups were higher than before management； meanwhile， the observation group was significantly higher than control group at the corresponding period （P＜0.05 or P＜ 0.01）. The blood pressure levels of both groups were significantly lower than before management， and the systolic blood pressure as well as the incidences of the whole complications and cerebrovascular injury in the observation group were significantly lower than control group at the 583867635@qq.com corresponding period （P＜0.05）. There was statistical significance in the effects of the rate of reaching the standard of blood pressure on the complications （P＜0.01）. CONCLUSIONS The hypertension management mode of comprehensive management team collaborated with community pharmacists can significantly improve the compliance and blood pressure compliance rate of elderly patients with hypertension， and reduce the incidence of hypertension-related complications.

BACKGROUND:The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment.On the other hand,although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization,the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE:To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS:SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions(Fe2+)and divalent cobalt ions(Co2+)(Fe-Co/ZIF-8@SLC-0111)was synthesized by ion-exchange reaction and self-assembly,and loaded with hyaluronic acid(HA)by electrostatic adsorption,followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA(abbreviated as FC-S).Meanwhile,nanoparticles Fe-Co/ZIF-8-HA(abbreviated as FC)without SLC-0111 were synthesized by the same method.The nanocomposite platform was tested for particle size,zeta potential,surface morphology,in vitro reactive oxygen species generation,and ability to consume glutathione.Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects.The cytotoxicity of FC-S was detected by CCK-8 assay.Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S.In addition to H2O2,the effects of FC-S and FC on intracellular pH,carbonic anhydrase 9 protein expression,cell viability and apoptosis,intracellular reactive oxygen species and glutathione content,and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION:(1)The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure,uniform size and good dispersion.Its particle size was about 323 nm;zeta potential was about-11.1 mV,and the nanoplatform had a certain reactive oxygen species generation capacity in vitro.(2)FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes.When the mass concentration of FC-S was≤20 μg/mL,there was no obvious cytotoxicity to MG-63 cells and L929 cells,and 20 μg/mL FC-S was selected to act on MG-63 cells in subsequent experiments.(3)Compared with FC group,the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased(P<0.01);the intracellular acidic environment was enhanced;the content of reactive oxygen species was increased(P<0.001);the mitochondrial damage was aggravated;the number of dead cells was increased,and the apoptosis rate was increased(P<0.001).(4)The results indicate that FC-S,as a novel composite nanoplatform,can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production,thus enhancing the efficacy of chemodynamic therapy.

Objective To explore the effect and molecular mechanism of cabozantinib combined with programmed cell death-ligand 1(PD-L1)monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods Subcutaneous tumor-bearing model was constructed using mouse hepatoma cells Hepa1-6.Model mice were divided into the control group,cabozantinib treatment group,PD-L1 monoclonal antibody treatment group,and cabozantinib+PD-L1 monoclonal antibody treatment group according to the intervention methods.The tumor growth rate of mice in each group was analyzed;the proportion of T cell infiltration in tumor tissues of mice in each group was detected by flow cytometry.Multicolor immunofluorescence was used to analyze the infiltration of T cells in tumor tissues of mice in each group.The expression levels of cytokines in the serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA).Results The inhibitory effect of the cabozantinib+PD-L1 monoclonal antibody on the tumorigenic ability of hepatoma cells in vivo was significantly stronger than that of the cabozantinib or PD-L1 monoclonal antibody.The results of flow cytometry and multicolor immunofluorescence detection showed that the proportion of CD8+T cells in the tumor tissues of the cabozantinib+PD-L1 monoclonal antibody treatment group was significantly higher than that of the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of TNF-α,IFN-γ and IL-6 in the serum of mice in the cabozantinib+PD-L1 monoclonal antibody treatment group were significantly higher than those in the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of the in vivo tumorigenesis experiment showed that the CD8 antibody could antagonize the inhibitory effect of cabozantinib combined with PD-L1 on the tumorigenic ability of mouse hepatoma cells.Conclusion Cabozantinib may enhance the anti-hepatocellular carcinoma effect of PD-L1 by recruiting CD8+T cells,and is expected to become a new strategy to enhance the effect of anti-tumor immunotherapy.

Objective To explore the effect and molecular mechanism of cabozantinib combined with programmed cell death-ligand 1(PD-L1)monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods Subcutaneous tumor-bearing model was constructed using mouse hepatoma cells Hepa1-6.Model mice were divided into the control group,cabozantinib treatment group,PD-L1 monoclonal antibody treatment group,and cabozantinib+PD-L1 monoclonal antibody treatment group according to the intervention methods.The tumor growth rate of mice in each group was analyzed;the proportion of T cell infiltration in tumor tissues of mice in each group was detected by flow cytometry.Multicolor immunofluorescence was used to analyze the infiltration of T cells in tumor tissues of mice in each group.The expression levels of cytokines in the serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA).Results The inhibitory effect of the cabozantinib+PD-L1 monoclonal antibody on the tumorigenic ability of hepatoma cells in vivo was significantly stronger than that of the cabozantinib or PD-L1 monoclonal antibody.The results of flow cytometry and multicolor immunofluorescence detection showed that the proportion of CD8+T cells in the tumor tissues of the cabozantinib+PD-L1 monoclonal antibody treatment group was significantly higher than that of the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of TNF-α,IFN-γ and IL-6 in the serum of mice in the cabozantinib+PD-L1 monoclonal antibody treatment group were significantly higher than those in the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of the in vivo tumorigenesis experiment showed that the CD8 antibody could antagonize the inhibitory effect of cabozantinib combined with PD-L1 on the tumorigenic ability of mouse hepatoma cells.Conclusion Cabozantinib may enhance the anti-hepatocellular carcinoma effect of PD-L1 by recruiting CD8+T cells,and is expected to become a new strategy to enhance the effect of anti-tumor immunotherapy.

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.

Spinal cord injury (SCI) is a disabling and destructive central nervous system injury that has not yet been successfully treated at this stage. Three-dimensional (3D) bioprinting has become a promising method to produce more biologically complex microstructures, which fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells, and this is critical in the treatment of SCI. With the development of 3D printing technology and the deepening of research, neural tissue engineering research using different printing methods, bio-inks, and cells to repair SCI has achieved certain results. Although satisfactory results have not yet been achieved, they have provided novel ideas for the clinical treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focuses on 3D bioprinting methods widely used in SCI neural tissue engineering, and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. In addition to introducing the recent progress, this work also describes the existing limitations and highlights emerging possibilities and future prospects in this field.