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OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

OBJECTIVE: To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). METHODS: A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. RESULTS: Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated. CONCLUSIONS Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

Objective To investigate the effect of tamoxifen on the estrogen receptor α36 (ERα36) in breast cancer patients and its mechanism.Methods The patients with breast cancer treated from January 2010 to January 2015 were randomly selected.Among the 100 patients treated with tamoxifen,20 mg · d-1 tamoxifen was given daily for the treatment group.And receive starch slices of 100 patients,as the control group.After 5 d of treatment,ERα36 cells were sorted out of the breast cancer suppressor cell population of the two groups by fluorescence activated cell sorting device from the ERα36 membrane-targeting receptor.The expression of ERα36 was detected by immunohistochemistry.Then the proliferation and metastasis of ERα36 cells were compared between the two groups.Finally,combined with disease-free surial (DSF) and average no transfer surial (MFS) in two groups.Results The positive expression of ERα36 in treatment group and control group were 42,53 cases;the less than 2 cm in tumor size in the 2 group were 11,24 cases;comparison between two groups,the difference was statistically significant (all P ＜ 0.05).It indicating that the expression of ERα36 was associated with the deterioration of breast cancer cells.Of the treatment group of patients with 58 cases of metastatic cases,significantly higher than the control group of 42 cases,and the treatment group died in 28 cases,while the control group died in 19 cases,the difference was statistically significant between the 2 groups (all P ＜ 0.05).Multivariate regression analysis showed that tamoxifen treatment was negatively correlated with DFS and MFS in these patients.It indicating that compared with the absence of tamoxifen treatment,the prognosis of patients treated with tamoxifen was worse,and the mortality and metastasis were higher in patients treated with tafloxacin,the absence of metastatic survival of ERα36 tumors treated with tamoxifen was significantly shorter.Conclusion Selective tamoxifen will result in acquired and primary drug resistance in breast cancer patients,with significant side effects on ERα36 in patients with breast cancer.

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Adolescent ; Adult ; Anesthesia, General ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Septal Defects, Atrial ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Septal Occluder Device ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the epidemiological features of severe chest trauma (SCT) and investigate the risk factor of its mortality in the Three Gorges Area of China.

METHODSThe clinical data of 1834 SCT patients who were admitted in three hospitals in this area from January 1990 to December 2009 were retrospectively reviewed. Th epidemiological features of SCT were analyzed using a database. Stepwise logistic regression analysis was used to analyze 15 possible risk factors affecting mortality.

RESULTSThe morbidity rates of blunt trauma (68.5% vs. 74.7%,p=0.006) and sharp instrument injury (12.2% vs. 15.9%,p=0.039) showed significant differences before and after 2000. The pre-hospital time [(3.45±2.38)h vs. (2.20±4.39)h,p<0.01] and transfer rate (32.39% vs. 36.80%,p=0.01) significantly improved. The thoracic Abbreviated Injury Scale (AIS)(3.56±0.71vs. 3.43±0.58,p<0.01)score and Revised Trauma Score (RTS)(7.14±2.18 vs. 6.93±1.07,p<0.01) significantly increased. Treatment for pulmonary infection (12.63±4.79 vs. 17.16±6.41,p=0.019) and hemorrhagic shock (2.4±0.75 vs. 3.4±1.34,p=0.008 )was significantly improved. The leading cause of death was hypovolemic shock (59.41%). The independent rik factors of death among these SCT patients included: hemorrhagic shock (B=1.710,OR=1.291,p=0.001), multiple organ dysfunction syndrome (B=3.453,OR=1.028,p<0.001), pulmonary infection(B=2.396,OR=10.941,p<0.001), abdominal organ injury(B=1.542,OR=1.210,p=0.005), and thorax AIS(B=0.487,OR=1.622,p<0.001).

CONCLUSIONSThe prevalence of SCT shows an increasing trend in the Three Gorges Area in recent years, but with a decreased rate of complications and improved treatment. Age, complications, thorax AIS, and GCS are useful prognostic indicators.

China ; epidemiology ; Humans ; Logistic Models ; Retrospective Studies ; Thoracic Injuries ; epidemiology ; mortality

Objective To explore the effect of continue nursing out of hospital on the rehabilitation patients with first onset schizophrenia and to provide theoretical guidance for the development of hospital extended care.Methods Totals of 120 patients with first onset schizophrenia were randomly divided into study group and control group,each group 60 cases. Study group received continue nursing interventions out of hospital in two stages,control group only received conventional treatment,nursing,discharge instruction,and followed up one year.Medication compliance,disease recurrence and reemployment of patients were recorded.After patients discharged six months and one year,they were investigated with Brief psychotic symptoms scale (BPRS) and comprehensive assessment of quality of life questionnaire (GQOLI-74).Results In study group,there was 39 patients complied doctors' advice,7 patients' disease recurred and 13 patients were reemployment,while 26 patients complied doctors' advice,17 patients' disease recurred and 4 patients were reemployment in control group,and the differences were statistically significant (x2 =5.673,5.208,5.551,respectively;P＜0.05).There was no significant difference on the BPRS scores in two groups before implemented continue nursing outside hospital ( P ＞ 0.05 ) ; while after implemented continue nursing,the total score of BPRS in study group was (54.34 ± 6.608 ) higher than ( 43.63 ± 5.47 ) in control group,and the differences were statistically significant(t =6.749,P ＜ 0.01 ).One year later,the EQOL-74 score in physical function (62.14 ± 7.16),psychological function ( 61.54 ± 7.14) and social function ( 60.42 ± 5.28 ) in study group were higher than that of control group that was (62.14 ± 7.16),( 61.54 ± 7.14 ),( 60.42 ± 5.28 )respectively,and the differences were statistically significant ( t =3.304,3.259,3.959,respectively; P ＜ 0.01 ).Comparison of medication compliance,and ratio between two groups,the differences were statistically significant (P ＜ 0.05).Condusions Continue nursing care can improve the social function of patients with first onset schizophrenia,improve their quality of life,promote their recovery and return to society.

OBJECTIVETo investigate the polymorphisms of cluster of differentiation 14(CD14)gene promoters and explore whether such polymorphisms are associated with the susceptibility to multiple organ dysfunction syndrome(MODS) in Chongqing population.

METHODSThe single nucleotide polymorphisms of the promoter region of CD14 gene at position -1145 and -159 were detected using polymerase chain reaction-restriction fragment length polymorphism method in 106 patients with severe chest trauma, among whom 47 were with MODS.

RESULTSTrauma patients carrying G allele tended to have a higher risk of MODS than those carrying A allele at position-1145, the MODS scores in trauma patients carrying G allele were significantly higher than those carrying A allele (P=0.217 for dominant effect and P=0.037 for recessive effect), and the MODS scores in trauma patients carrying T allele were significantly higher than those carrying C allele at position -159 (P=0.048 for dominant effect and P=0.198 for recessive effect). The genotypes of CD14 gene at positions -1145 and -159 were significantly correlated with the MODS scores (P=0.043,P=0.046). Compare with single-point mutation, simultaneous two-point mutation had significantly higher risk of MODS (Pü0.01), while the difference of MODS scores showed no statistical significance (P=0.239).

CONCLUSIONThe polymorphisms of CD14 gene promoters are associated with MODS after severe chest trauma in Chongqing population.

Adult ; Female ; Genotype ; Humans ; Lipopolysaccharide Receptors ; genetics ; Male ; Multiple Organ Failure ; etiology ; genetics ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; Thoracic Injuries ; complications

BACKGROUNDEnhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+).

METHODSGrowth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively.

RESULTSA porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P < 0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P < 0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P < 0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups.

CONCLUSIONSThe results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.

Animals ; Arteriosclerosis ; physiopathology ; Blotting, Western ; Chemokine CXCL12 ; metabolism ; Counterpulsation ; methods ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Granulocyte Colony-Stimulating Factor ; blood ; metabolism ; Humans ; Hypercholesterolemia ; metabolism ; surgery ; Immunohistochemistry ; Male ; Myocardium ; metabolism ; Neovascularization, Pathologic ; metabolism ; surgery ; Random Allocation ; Recombinant Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; cytology ; Swine ; Vascular Endothelial Growth Factor A ; blood ; metabolism

Adult ; Epithelioid Cells ; pathology ; Fatal Outcome ; Female ; Humans ; Hysterectomy ; Middle Aged ; Trophoblastic Neoplasms ; pathology ; surgery ; Uterine Neoplasms ; pathology ; surgery