OBJECTIVE To explore the ameliorative effect and potential mechanism of vitexin on inflammation in ulcerative colitis （UC） mice. METHODS The UC mice model was established by continuous administration of 3% dextran sulfate sodium solution for 5 days. Mice with successful modeling were randomly divided into UC group， vitexin low- and high-dose groups （vitexin-L and vitexin-H groups， 40， 80 mg/kg）， mesalazine group （400 mg/kg）， and vitexin-H+recombinant Jagged canonical Notch ligand 1 （rJagged-1） group （vitexin-H+rJagged-1 group， 80 mg/kg vitexin+1 mg/kg rJagged-1）， with 12 mice in each group. Another 12 normal mice were used as the control （CK） group. Mice in each group were administered the corresponding drugs or the corresponding drugs and normal saline by gavage and intraperitoneal injection once daily for 7 consecutive days. General conditions were observed during the experiment. At 24 h after the last administration， the disease activity index （DAI） score was evaluated. Colonic histopathological morphology was observed and scored. Macrophage polarization levels in the spleen and colon tissues were measured. The protein expressions of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， transforming growth factor-β 1 （TGF-β 1 ）， Jagged-1， Notch1 and Notch intracellular domain （NICD） in colonic tissues were determined. RESULTS Compared with the UC group， the symptoms （reduced food and water intake， dull fur， etc.） and pathological changes （epithelial cell shedding， inflammatory cell infiltration， etc.） were significantly improved in the vitexin-L， vitexin-H and mesalazine groups. DAI scores， colonic histopathological scores， M1 macrophage contents in spleen tissue， M1/M2 macrophage ratios， M1 macrophage proportions in colon tissue， and protein expressions of IL-6， TNF-α， Jagged-1， Notch1 and NICD in colon tissue were significantly decreased （ P ＜0.05）. Meanwhile， the M2 macrophage contents in spleen tissue， M2 macrophage proportions in colon tissue， and protein expressions of IL-10 and TGF-β 1 in colon tissue were significantly increased （ P ＜0.05）. Moreover， the improvement effects in the vitexin-H and mesalazine groups were significantly superior to those in the vitexin-L group （ P ＜0.05）. Compared with the vitexin-H group， the above symptoms and pathological changes were aggravated， and all quantitative indicators were significantly reversed in the vitexin-H+rJagged-1 group （ P ＜0.05）. CONCLUSIONS Vitexin can ameliorate the inflammation of UC mice， which is associated with its inhibition of the Jagged-1/Notch1 pathway and regulation of macrophage polarization （inhibition of M1-type polarization and promotion of M2-type polarization）.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

The paper summarizes the authorized invention patents, device registration and the relevant published articles of acupuncture medical devices of TCM in recent 5 years, and analyzes the current status and challenges in this field. It is discovered that the optimization and substitution in diagnosis and treatment of acupuncture are involved in the development of acupuncture medical devices. The technology application of these devices are composed of traditional and emerging engineering technologies; and the theoretical guidance for their development requires the integration of traditional acupuncture principles with modern medical theories. The development of acupuncture medical devices highlights the characteristics of multidimensional integration, treatment for specific ailments, portability and wearability, painlessness and non-invasion, precision and personalization, as well as intelligent automation. Upon analysis, it is shown that in the development and product transformation of acupuncture medical devices in recent years, the theoretical principles of acupuncture of TCM have not been fully utilized yet, the transformation of patented product is low, the clinical evidence of product is insufficient, and the market competitiveness needs improvement. In the future, The theoretic guidance of acupuncture of TCM should be enhanced in the development of acupuncture medical devices, a production-education- research model with the combination of medicine and engineering be constructed, clinical verification of product be emphasized, and product development paradigms be advanced, so as to meet the demands of the medical market.
Acupuncture Therapy/trends* ; Humans ; Medicine, Chinese Traditional/instrumentation* ; Equipment and Supplies

To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology* ; Atractylodes/microbiology* ; Phylogeny ; Plant Roots/microbiology* ; Fusarium/classification* ; China ; Virulence ; Fungal Proteins/genetics*