Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes were found to be effective in promoting neural repair in spinal cord injury.OBJECTIVE:To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells are able to attenuate neuroinflammation and promote recovery of motor function by promoting polarization of microglia toward the M2 type.METHODS:Totally 48 SD rats were randomly divided into a sham operation group,a model group,and an exosome group(n=16 per group).A rat spinal cord injury model was established using the modified Allen method.The exosome group was injected with 20 μL of human umbilical cord mesenchymal stem cell-derived exosomes intrathecally via neuroendoscopy 24 hours after injury.At 3,7,14,and 21 days after modeling,the recovery of the motor function of the hind limbs of the rats was assessed by BBB scoring method combined with Rivlin's slant plate test.The damage of spinal cord tissues was detected by using hematoxylin-eosin staining and Nissl staining.The expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor A proteins were detected by western blot assay.The expression proportion of M1-type markers(inducible nitric oxide synthase)and M2 markers(arginase-1)in the spinal cord tissues was detected by immunofluorescence method.qRT-PCR and western blot assay were used to detect the expression levels of inducible nitric oxide synthase and arginase-1 in spinal cord tissues.ELISA was utilized to detect the levels of pro-inflammatory factors(tumor necrosis factor α,interleukin 1β,and interleukin 6)and anti-inflammatory factors(interleukin 10)levels in spinal cord tissues.RESULTS AND CONCLUSION:(1)At 3,7,and 14 days postoperatively,the BBB scores of the exosome group were better than those of the model group(P＜0.05).The angles of the Rivlin slanting plate experiments of the exosome group were significantly higher than those of the model group at 7 and 14 days postoperatively(P＜0.05).The results of hematoxylin-eosin staining and Nissl staining indicated that the spinal cord tissues and nerve injuries of the exosome group were reduced in comparison with those of the model group,and the levels of brain-derived neurotrophic factor and vascular endothelial growth factor A in spinal cord tissues of the exosome group were higher than those in the model group at 7 days postoperatively(P＜0.05).(2)Immunofluorescence experiments showed that the number of inducible nitric oxide synthase-positive microglial cells in the lesion area of the exosome group was significantly reduced and the level of Arg1-positive microglial cells increased in the lesion area of the exosome group compared with the model group at 7 days postoperatively(P＜0.05).qRT-PCR and western blot assay also confirmed the results of immunofluorescence experiments.(3)The secretion of pro-inflammatory factors tumor necrosis factor α,interleukin 1β,and interleukin 6 in spinal cord tissues of the exosome group was reduced compared with the model group(P＜0.05),whereas the secretion of the inflammation-suppressing factor interleukin 10 was increased compared with the model group(P＜0.05).These findings conclude that human umbilical cord mesenchymal stem cell-derived exosomes could promote the polarization of microglial cells from the M1 to the M2 type and decrease the release of pro-inflammatory factors,thereby reducing the secondary damage of neuroinflammation in spinal cord injury.

BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes were found to be effective in promoting neural repair in spinal cord injury.OBJECTIVE:To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells are able to attenuate neuroinflammation and promote recovery of motor function by promoting polarization of microglia toward the M2 type.METHODS:Totally 48 SD rats were randomly divided into a sham operation group,a model group,and an exosome group(n=16 per group).A rat spinal cord injury model was established using the modified Allen method.The exosome group was injected with 20 μL of human umbilical cord mesenchymal stem cell-derived exosomes intrathecally via neuroendoscopy 24 hours after injury.At 3,7,14,and 21 days after modeling,the recovery of the motor function of the hind limbs of the rats was assessed by BBB scoring method combined with Rivlin's slant plate test.The damage of spinal cord tissues was detected by using hematoxylin-eosin staining and Nissl staining.The expression levels of brain-derived neurotrophic factor and vascular endothelial growth factor A proteins were detected by western blot assay.The expression proportion of M1-type markers(inducible nitric oxide synthase)and M2 markers(arginase-1)in the spinal cord tissues was detected by immunofluorescence method.qRT-PCR and western blot assay were used to detect the expression levels of inducible nitric oxide synthase and arginase-1 in spinal cord tissues.ELISA was utilized to detect the levels of pro-inflammatory factors(tumor necrosis factor α,interleukin 1β,and interleukin 6)and anti-inflammatory factors(interleukin 10)levels in spinal cord tissues.RESULTS AND CONCLUSION:(1)At 3,7,and 14 days postoperatively,the BBB scores of the exosome group were better than those of the model group(P＜0.05).The angles of the Rivlin slanting plate experiments of the exosome group were significantly higher than those of the model group at 7 and 14 days postoperatively(P＜0.05).The results of hematoxylin-eosin staining and Nissl staining indicated that the spinal cord tissues and nerve injuries of the exosome group were reduced in comparison with those of the model group,and the levels of brain-derived neurotrophic factor and vascular endothelial growth factor A in spinal cord tissues of the exosome group were higher than those in the model group at 7 days postoperatively(P＜0.05).(2)Immunofluorescence experiments showed that the number of inducible nitric oxide synthase-positive microglial cells in the lesion area of the exosome group was significantly reduced and the level of Arg1-positive microglial cells increased in the lesion area of the exosome group compared with the model group at 7 days postoperatively(P＜0.05).qRT-PCR and western blot assay also confirmed the results of immunofluorescence experiments.(3)The secretion of pro-inflammatory factors tumor necrosis factor α,interleukin 1β,and interleukin 6 in spinal cord tissues of the exosome group was reduced compared with the model group(P＜0.05),whereas the secretion of the inflammation-suppressing factor interleukin 10 was increased compared with the model group(P＜0.05).These findings conclude that human umbilical cord mesenchymal stem cell-derived exosomes could promote the polarization of microglial cells from the M1 to the M2 type and decrease the release of pro-inflammatory factors,thereby reducing the secondary damage of neuroinflammation in spinal cord injury.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective To explore the mediating effect of facial emotion recognition on prosocial behavior of medical students in mask-obscured scenes.Methods Fifty-three medical students from a medical university in Chongqing were enrolled from July to September 2023 to complete the facial emotion recognition task,the dictator gaming task and the state empathy test.Spearman correlation analysis was used to examine the correlation between mask wearing and state empathy,trait empathy and prosocial behaviours,and the PROCESS procedure was used to test the mediation of state empathy and the moderating effect of mask wearing or not.Results ①mask wearing,state empathy and prosocial behaviour were significantly correlated(P＜0.01);② State empathy exerted mediated effect between facial emotion recognition and prosocial behavior,with the largest effect size(47％)for the relative mediating effect of sadness;③The interaction terms of facial emotion recognition and mask wearing had a significant effect on state empathy(P＜0.05).Conclusion Facial emotion recognition can influence prosocial behavior directly and also exert indirect effect on prosocial behavior through state empathy.Compared to the condition without mask wearing,mask wearing can significantly facilitate the effect of happy,sad and neutral emotions on state empathy.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Glioma serves as a highly complex and lethal brain tumor,its treatment has been a major challenge in neurosurgery and oncology.In recent years,the in-depth studies of glioma microenvironment have provided new perspectives for understanding its pathogenesis and developing new therapeutic strategies.This article introduces the major components of glioma microenvironment,regulation signaling pathways and possi-ble therapeutic targets,aiming to provide a comprehensive perspective to understand and treat this complex tumor and emphasizing the importance of the glioma microenvironment in glioma research and treatment.

Objective:To evaluate the quality of the published breast cancer screening guidelines to provide a reference for domestic studies in the future.Methods:PubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched to identify breast cancer screening guidelines on until August 2020. Two reviewers screened literature and extracted data independently. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREEⅡ) and Reporting Items for Practice Guidelines in Healthcare(RIGHT) tools were used to evaluate the quality of the included guidelines.Results:A total of 15 breast cancer screening guidelines were included, of which seven were published in the United States, with publication years focusing on 2015 to 2019, and 11 guidelines had updated versions. "Rigour of development" (47.0%±22.1%) and "Applicability" (44.0%±15.1%) of AGREEⅡ scored lower than other domains. "Review and quality assurance" (46.7%±39.9%) and "Funding, declaration, and management of interests" (41.7%±24.4%) of RIGHT were reported poorer than others. There were six guidelines recommended and another nine recommended with modifications based on the overall AGREEⅡ score. There were four guidelines with a good level, and another 11 were with a moderate level of RIGHT. The National Comprehensive Cancer Network published the best overall quality guidelines in 2018 (AGREEⅡ: 83.3%, RIGHT: 80.0%) and by the American Cancer Society in 2015 (AGREEⅡ: 83.3%, RIGHT: 85.7%).Conclusion:The quality of breast cancer screening guidelines was predominantly of moderate quality, and greater attention should be paid to the guideline development process and quality control of the guidelines.