The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVES: To investigate the predictive value of myocardial strain for cardiotoxicity associated with fluorouracil-based chemotherapies in gastrointestinal cancer patients. METHODS: Patients with diagnosis of gastrointestinal cancers, who were hospitalized for chemotherapy involving antimetabolic drugs, were eligible in this prospective study. Echocardiography was performed before and after each chemotherapy cycle during hospitalization until the completion of chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) was identified if there was a decrease in left ventricular ejection fraction (LVEF) by at least 5% to an absolute value of < 53% from the baseline, accompanied by symptoms or signs of heart failure; or a decrease in LVEF of at least 10% to an absolute value of < 53% from the baseline, without symptoms or signs of heart failure. Subclinical cardiac impairment is defined as a decrease in the left ventricular global longitudinal strain (GLS) of at least 15% from baseline.Clinical data and myocardial strain variables were collected. Changes of echocardiographic indexes after chemotherapy at each cycle were observed and compared to those of pre-chemotherapy. Cox regression analysis was used to determine the associated indexes to CTRCD, and receiver operating characteristic (ROC) curves were plotted for evaluation of their predicting efficacy. RESULTS: Fifty-one patients completed 4 cycles of chemotherapy and were enrolled in the study analysis. LVEF, GLS, GLS epicardium (GLS-epi), and GLS endocardium (GLS-endo) were decreased after the 4 cycles of chemotherapy. Throughout the chemotherapy period, 6 patients (11.8%) progressed to CTRCD. The Cox regression analysis revealed that the change in left atrial ejection fraction (LAEF) and LAS during the reservoir (LASr) phase after the first cycle of chemotherapy (C1v-LAEF and C1v-LASr, respectively) were significantly associated with the development of CTRCD [C1v-LAEF (HR=1.040; 95%CI: 1.000-1.082; P=0.047); C1v-LASr (HR=1.024; 95%CI: 1.000-1.048; P=0.048)]. The sensitivity and specificity were 50.0% and 93.3%, respectively, for C1v-LAEF predicting CTRCD when C1v-LAEF > 19.68% was used as the cut-off value, and were 66.7% and 75.6%, respectively, for C1v-LASr predicting CTRCD when C1v-LASr > 14.73% was used as the cut-off value. The areas under the ROC curve (AUC) for C1v-LAEF and C1v-LASr predicting CTRCD were 0.694 and 0.707, respectively. CONCLUSIONS GLS changes among patients with subclinical impairment of cardiac function who were treated with fluorouracil-based chemotherapies, and C1v-LAEF and C1v-LASr of the left atrium are early predictors of cardiac function deterioration.
Humans ; Fluorouracil/adverse effects* ; Male ; Female ; Middle Aged ; Gastrointestinal Neoplasms/drug therapy* ; Aged ; Echocardiography ; Prospective Studies ; Adult ; Heart/diagnostic imaging*

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate

OBJECTIVES: To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. METHODS: The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. RESULTS: After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). CONCLUSIONS The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.
Infant, Newborn ; Infant ; Child ; Humans ; Birth Weight ; Infant, Large for Gestational Age ; Infant, Small for Gestational Age ; Gestational Age ; Child Health

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective:To explore the protective effect and underlying mechanism of hyperbaric oxygen (HBO) on delayed encephalopathy after carbon monoxide poisoning (DEACMP) in mice.Methods:Totally 225 adult male Kunming mice were selected to establish CO poisoning model via intraperitoneal injection carbon monoxide (CO), and were randomly divided into the air control group, CO poisoning group, and HBO group. Each group was further divided into five time points group, that was 1, 3, 7, 14 and 21 d. The mice in the air control group were injected intraperitoneally with the same amount of air, and the HBO group received HBO treatment at the same time every day. DEACMP mice model was screened by behaviors using the open field test, new object recognition test and nesting test, and the content of myelin basic protein (MBP) were assayed. The mouse brain tissue and mitochondrial were prepared and malonialdehyde (MDA) and adenosine triphosphate (ATP) content were measured with ultraviolet spectrophotometer. MBP content in brain tissue and cytochrome C (CytC) content in the mitochondrial were measured by ELISA. The mitochondria membrane potential (MMP) was measured by flow cytometry.Results:Compared with the air control group, the content of carboxyhemoglobin (COHB) in blood increased significantly and the content of MBP in brain tissue decreased significantly in CO poisoning mice. CO poisoning mice showed motor ability and cognitive dysfunction. Compared with the air control group, the contents of MMP, CytC and ATP were significantly decreased ( P<0.01) in the CO poisoning group; while the MDA content was significantly increased ( P<0.01). Compared with the CO poisoning group, mice behaviors were improved significantly ( P<0.05), the content of MBP, MMP, CytC and ATP were increased ( P<0.05), while the MDA content decreased significantly ( P<0.01) in the HBO group. Conclusions:The abnormal mitochondrial function might be closely related to the occurrence and development of DEACMP, and HBO therapy plays an effective role in preventing and treating the DEACMP mice model via the mitochondrial pathway.