ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

Objective To explore the application value of serum heat shock protein 90α(Hsp90α)combined with β2-microglobulin(β2-MG)detection in the early diagnosis and prognosis of colorectal cancer(CRC).Methods A total of 101 patients with CRC who received their first treatment were selected as the CRC group(no surgery,radiotherapy or chemotherapy before enrollment),100 patients with benign colon tumor admitted to our hospital during the same period were selected as the benign tumor group and 94 healthy individuals who underwent physical examinations in our hospital were used as the control group.The levels of serum Hsp90α and β2-MG in all subjects were detected by ELISA.Follow-up was conducted every three months within the first two years after surgery,and every six months in the third year,for a total follow-up period of 3 years,and the survival status of CRC patients within 3 years was recorded.ROC curve analysis was used to evaluate the diagnostic value of serum Hsp90α and β2-MG for CRC.The Kaplan-Meier method was used to draw the survival curves of CRC patients with different expression levels of Hsp90α and β2-MG.Results The serum levels of Hsp90α and β2-MG increased successively in the control group,the benign tumor group and the CRC group(P＜0.05).There were no significant differences in serum levels of Hsp90α and β2-MG between CRC patients of different genders,ages and lesion locations.The levels of serum Hsp90α and β2-MG in patients with tumor diameter＞5 cm,low differentiation degree,TNM stage Ⅲ and lymph node metastasis were higher than those in patients with tumor diameter≤5 cm,moderate to high differentiation degree,TNM stage Ⅰ-Ⅱ and no lymph node metastasis(P＜0.05).The ROC results showed that the combined diagnostic efficacy of serum Hsp90α and β2-MG was superior to that of serum Hsp90α or β2-MG alone(Z=2.433,2.435,P＜0.05).Based on the average expression levels of serum Hsp90α and β2-MG in CRC patients(76.66 μg/L and 6.52 μg/L),patients were divided into the high expression group of Hsp90α(59 cases),the low expression group of Hsp90α(42 cases),the high expression group of β2-MG(63 cases)and the low expression group of β2-MG(38 cases).Among the 101 CRC patients,31 died and 70 survived,with a total survival rate of 69.31％.The Kaplan-Meier survival curve showed that the 3-year survival rates of patients with high expression levels of Hsp90α and β2-MG were lower than theose of patients with low expression levels of Hsp90α and β2-MG(P＜0.01).Conclusion The expression levels of serum Hsp90α and β2-MG are both elevated in CRC patients,and they are closely related to the occurrence,development and prognosis of CRC.

Objective:To identify HLA-G-binding proteins(HGBPs)by screening targeting ankyrin sequences from a phage display-based ankyrin protein library using human leukocyte antigen G(HLA-G)as the target,and to evaluate their functions.Methods:The expression of HLA-G in tumor tissues and its correlation with clinical prognosis and immune infiltration were analyzed using bioinformatics tools such as TCGA and GTEx databses.The extracellular domain of HLA-G was subjected to biopanning with a phage-displayed ankyrin protein library,followed by random selection and sequencing of monoclonal phage clones.The functional properties of dominant phage clones were validated using ELISA and immunofluorescence staining.HGBPs were produced and purified using a prokaryotic expression system,and their affinity and tumor-specific binding ability were evaluated using ELISA,surface plasmon resonance(SPR),and immunofluorescence staining.Results:Bioinformatics analysis revealed that HLA-G is widely overexpressed in tumor tissues and is correlated with overall survival(OS)and immune cell infiltration(P<0.05).After five rounds of biopanning,dominant clones were obtained.Both ELISA and immunofluorescence staining results showed that these dominant phages had a significantly higher affinity to HLA-G positive cells compared to HLA-G negative cells(P<0.05,P<0.001).The purified HGBPs exhibited an affinity of up to 17 nmol/L for HLA-G.ELISA results showed significant binding of HGBP to HLA-G(P<0.05),and immunofluorescence staining confirmed that HGBP could specifically bind to HLA-G-positive cells(P<0.01).Conclusion:The HGBPs identified via phage display exhibit high affinity and specificity to HLA-G on tumor cells.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Objective To observe the clinical efficacy and safety of filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome.Methods Seventy patients with acne of damp-heat due to spleen deficiency syndrome admitted to the seventh clinical Medical School of Guangzhou University of Chinese Medicine from May 2023 to March 2024 were randomly divided into the observation group and the control group according to random number table method,with 35 patients in each group.Health education was given to the patients in both groups.The control group was given oral administration of Doxycycline Hyclate Tablets combined with filiform-heated needle for treatment,and the observation group was treated with filiform-heated needle combined with Qingbu Huacuo Decoction orally,the course of treatment for the two groups covered six weeks.After six weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in Global Acne Grading System(GAGS)score and Quality of Life-Acne(Qol-Acne)score,as well as the traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed.The changes of skin barrier function indicators such as trans epidermal water loss(TEWL)content,skin moisture content,and sebum content before and after treatment were compared between the two groups of patients.Moreover,the safety of the two groups and the occurrence of adverse reactions were evaluated.Results(1)After treatment,the GAGS scores of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(2)After treatment,the Qol-Acne scores of the patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the three aspects of self-perception,emotional functioning,and self-assessment,with a statistically significant difference(P<0.05),and the observation group was slightly superior to the control group in improving social functioning,but the difference being not statistically significant(P>0.05).(3)After treatment,the content of TEWL,skin moisture,and sebum of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TCM syndrome scores of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(5)The total effective rate was 94.29%(33/35)in the observation group and 74.29%(26/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(6)Comparison of the incidence of adverse reactions between the two groups,the difference being not statistically significant(P>0.05).Conclusion Filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome can significantly improve the clinical symptoms of patients,thus improving their quality of life,with good safety.

Objective To explore the application value of serum heat shock protein 90α(Hsp90α)combined with β2-microglobulin(β2-MG)detection in the early diagnosis and prognosis of colorectal cancer(CRC).Methods A total of 101 patients with CRC who received their first treatment were selected as the CRC group(no surgery,radiotherapy or chemotherapy before enrollment),100 patients with benign colon tumor admitted to our hospital during the same period were selected as the benign tumor group and 94 healthy individuals who underwent physical examinations in our hospital were used as the control group.The levels of serum Hsp90α and β2-MG in all subjects were detected by ELISA.Follow-up was conducted every three months within the first two years after surgery,and every six months in the third year,for a total follow-up period of 3 years,and the survival status of CRC patients within 3 years was recorded.ROC curve analysis was used to evaluate the diagnostic value of serum Hsp90α and β2-MG for CRC.The Kaplan-Meier method was used to draw the survival curves of CRC patients with different expression levels of Hsp90α and β2-MG.Results The serum levels of Hsp90α and β2-MG increased successively in the control group,the benign tumor group and the CRC group(P＜0.05).There were no significant differences in serum levels of Hsp90α and β2-MG between CRC patients of different genders,ages and lesion locations.The levels of serum Hsp90α and β2-MG in patients with tumor diameter＞5 cm,low differentiation degree,TNM stage Ⅲ and lymph node metastasis were higher than those in patients with tumor diameter≤5 cm,moderate to high differentiation degree,TNM stage Ⅰ-Ⅱ and no lymph node metastasis(P＜0.05).The ROC results showed that the combined diagnostic efficacy of serum Hsp90α and β2-MG was superior to that of serum Hsp90α or β2-MG alone(Z=2.433,2.435,P＜0.05).Based on the average expression levels of serum Hsp90α and β2-MG in CRC patients(76.66 μg/L and 6.52 μg/L),patients were divided into the high expression group of Hsp90α(59 cases),the low expression group of Hsp90α(42 cases),the high expression group of β2-MG(63 cases)and the low expression group of β2-MG(38 cases).Among the 101 CRC patients,31 died and 70 survived,with a total survival rate of 69.31％.The Kaplan-Meier survival curve showed that the 3-year survival rates of patients with high expression levels of Hsp90α and β2-MG were lower than theose of patients with low expression levels of Hsp90α and β2-MG(P＜0.01).Conclusion The expression levels of serum Hsp90α and β2-MG are both elevated in CRC patients,and they are closely related to the occurrence,development and prognosis of CRC.

Objectives:To investigate the predictive value of the hemoglobin to serum creatinine ratio(Hb/SCr)for all-cause mortality within 3 years after percutaneous coronary intervention(PCI)in patients with ST-segment elevation myocardial infarction(STEMI).Methods:A total of 687 STEMI patients who successfully underwent the first PCI at the Department of Cardiology,Gansu Provincial People's Hospital,from June 2016 to June 2020 were retrospectively enrolled.Patients were divided into survival and non-survival groups according to their vital status at 3 years post-PCI.Cox regression analysis was performed to identify predictive factors of all-cause mortality.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive value of Hb/SCr for all-cause mortality,and Kaplan-Meier survival curves were used to compare cumulative survival rates between subgroups stratified by Hb/SCr levels.Results:The median follow-up duration was 37(25,50)months.Among the 663 patients(96.51%)with complete follow-up data,41 cases(6.18%)experiencing all-cause death.Multivariable Cox regression analysis revealed that age(HR=1.086,95%CI:1.037-1.137,P=0.000),body mass index(HR=1.195,95%CI:1.128-1.266,P=0.000),fasting blood glucose(HR=1.069,95%CI:1.007-1.135,P=0.030),fibrinogen(HR=1.418,95%CI:1.120-1.795,P=0.004),TIMI flow grade 1(HR=4.968,95%CI:1.194-20.667,P=0.028),TIMI flow grade 2(HR=3.861,95%CI:1.336-11.156,P=0.013),and Hb/SCr(HR=0.858,95%CI:0.766-0.961,P=0.008)were the independent predictors of all-cause mortality.ROC curve analysis demonstrated that the area under the curve(AUC)of Hb/SCr was 0.721(95%CI:0.645-0.798)for predicting all-cause mortality,with a sensitivity of 65.9%and specificity of 71.2%,at the optimal cut-offvalue of 16.627.Kaplan-Meier analysis showed that patients with Hb/SCr<16.627 had significantly lower survival rates than those with Hb/SCr≥16.627(log-rank P=0.000).Conclusions:Hb/SCr is an independent predictor of 3-year all-cause mortality in STEMI patients after PCI and this indicator could be used as risk stratification parameter and patients with lower Hb/SCr might benefit comprehensive post-PCI management to improve their outcome.

Objectives:To investigate the predictive value of the hemoglobin to serum creatinine ratio(Hb/SCr)for all-cause mortality within 3 years after percutaneous coronary intervention(PCI)in patients with ST-segment elevation myocardial infarction(STEMI).Methods:A total of 687 STEMI patients who successfully underwent the first PCI at the Department of Cardiology,Gansu Provincial People's Hospital,from June 2016 to June 2020 were retrospectively enrolled.Patients were divided into survival and non-survival groups according to their vital status at 3 years post-PCI.Cox regression analysis was performed to identify predictive factors of all-cause mortality.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive value of Hb/SCr for all-cause mortality,and Kaplan-Meier survival curves were used to compare cumulative survival rates between subgroups stratified by Hb/SCr levels.Results:The median follow-up duration was 37(25,50)months.Among the 663 patients(96.51%)with complete follow-up data,41 cases(6.18%)experiencing all-cause death.Multivariable Cox regression analysis revealed that age(HR=1.086,95%CI:1.037-1.137,P=0.000),body mass index(HR=1.195,95%CI:1.128-1.266,P=0.000),fasting blood glucose(HR=1.069,95%CI:1.007-1.135,P=0.030),fibrinogen(HR=1.418,95%CI:1.120-1.795,P=0.004),TIMI flow grade 1(HR=4.968,95%CI:1.194-20.667,P=0.028),TIMI flow grade 2(HR=3.861,95%CI:1.336-11.156,P=0.013),and Hb/SCr(HR=0.858,95%CI:0.766-0.961,P=0.008)were the independent predictors of all-cause mortality.ROC curve analysis demonstrated that the area under the curve(AUC)of Hb/SCr was 0.721(95%CI:0.645-0.798)for predicting all-cause mortality,with a sensitivity of 65.9%and specificity of 71.2%,at the optimal cut-offvalue of 16.627.Kaplan-Meier analysis showed that patients with Hb/SCr<16.627 had significantly lower survival rates than those with Hb/SCr≥16.627(log-rank P=0.000).Conclusions:Hb/SCr is an independent predictor of 3-year all-cause mortality in STEMI patients after PCI and this indicator could be used as risk stratification parameter and patients with lower Hb/SCr might benefit comprehensive post-PCI management to improve their outcome.