Magnolol, a compound extracted from Magnolia officinalis, demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases. Its biological activities encompass anti-inflammatory, antioxidant, anticoagulant, and anti-diabetic effects. Growth/differentiation factor-15 (GDF-15), a member of the transforming growth factor β superfamily, is considered a potential therapeutic target for metabolic disorders. This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism. The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo, and determined the involvement of endoplasmic reticulum (ER) stress signaling in this process. Luciferase reporter assays, chromatin immunoprecipitation, and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4 (ATF4), CCAAT enhancer binding protein γ (CEBPG), and CCCTC-binding factor (CTCF). The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene, as well as the influence of single nucleotide polymorphisms (SNPs) on magnolol and ATF4-induced transcription activity. Results demonstrated that magnolol triggers GDF-15 production in endothelial cells (ECs), hepatoma cell line G2 (HepG2) and hepatoma cell line 3B (Hep3B) cell lines, and primary mouse hepatocytes. The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene. SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15. In high-fat diet ApoE^-/- mice, administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15. These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity, indicating its potential as a drug for the treatment of metabolic disorders.
Lignans/pharmacology* ; Growth Differentiation Factor 15/metabolism* ; Animals ; Biphenyl Compounds/pharmacology* ; Endoplasmic Reticulum Stress/drug effects* ; Activating Transcription Factor 4/genetics* ; Mice ; Humans ; Male ; Magnolia/chemistry* ; CCAAT-Enhancer-Binding Proteins/genetics* ; Mice, Inbred C57BL

Objective To investigate the effect of deoxyelephantopin(Deo)on regulation of cell apoptosis pathway by reactive oxygen species(ROS)in human non-small cell lung cancer A549 cells.Methods A549 cells were treated with different concentrations of Deo.Cell counting kit 8(CCK-8)assay was used to detect the cell viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)staining was used to measure cellular ROS content,and Hoechst 33342 staining was used to detect apoptotic bodies.Cell apoptosis and mitochondrial membrane potential were examined by flow cytometry.Quantitative polymerase chain reaction and Western blotting were used to detect the expression of apoptosis-related proteins.A549 xenograft tumor model in nude mice was used to evaluate the anti-tumor effect of Deo in vivo.Hematoxylin-eosin staining and TUNEL assay were used to observe the necrosis and cell apoptosis in tumor tissues.Results With the increase of Deo concentration(1,2,4,8,16,32 μmol/L),the viability of A549 cells showed a decreasing trend.Deo at 10 μmol/L could increase the ROS content in A549 cells,reduce mitochondrial membrane potential and promote cell apoptosis.Deo at 10 and 20 μmol/L promoted the mRNA and protein expression of Bax and caspase-3 and inhibited the mRNA and protein expression of Bcl-2,accompanied by significantly increased protein expression of cytochrome C in the cytoplasm.The volume and weight of transplanted tumor in nude mice were significantly inhibited after 17 d of administration of Deo of 10 and 20 mg·kg-1·d-1,and the necrotic area and the number of apoptotic cells in the tumor tissue were increased.Conclusion Deo can induce intracellular ROS production,and then activate the mitochondrial apoptosis pathway and consequently promote the apoptosis of A549 cells.

Objective:To exploring the application effect of doctors-nurses-patients theory of goal attainment combined with StMarys cluster intervention mode in patients with tracheotomy after stroke.Methods:Using convenient sampling method, a total of 130 stroke patients with tracheostomy who were admitted to Shangqiu First People's Hospital from August 2020 to February 2022 were selected as the research objects. The patients were divided into the control group and the observation group using the random number table method, with 65 cases in each group. The control group received routine nursing care, while the observation group applied doctors-nurses-patients theory of goal attainment combined with StMarys cluster nursing intervention mode on the basis of the control group. After intervention, scores of Self Rating Anxiety Scale (SAS) and Self Rating Depression Scale (SDS) and patient nursing satisfaction were compared between the two groups.Results:After intervention, the SAS and SDS scores of the observation group were lower than those of the control group, and the nursing satisfaction was higher than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The doctors-nurses-patients theory of goal attainment combined with StMarys cluster intervention mode can help improve the psychological state of patients and increase nursing satisfaction.

Objective:To evaluate the effects of left ventricular remodeling on systolic synchronization in patients with severe preeclampsia(SPE) by full-volume imaging technology.Methods:One hundred and nine patients with SPE were randomly selected as SPE group in the First Hospital of Shanxi Medical University from December 2016 to December 2019, which were further divided into systolic synchrony(SS) group ( n=35) and systolic dyssynchrony(SD) group( n=74). And 34 healthy pregnant women during the same period were selected as normal pregnancy(NP) group. The clinical datas were collected. Parameters including left ventricular end diastolic volume(LVEDV), left ventricular end systolic volume(LVESV), left ventricular ejection fraction(LVEF), spherical index(SpI), left ventricular mass index(LVMI) and systolic dyssynchrony index(SDI) were obtained by full-volume imaging technology. The effects of left ventricular remodeling on systolic synchronization in patients with SPE were analyzed by bivariate correlation, multiple linear stepwise regression analysis and binary Logistic regression analysis, respectively. Results:①Bivariate correlation analysis showed that LVEDV, LVESV, SpI and LVMI were positively correlated with SDI( r=0.335, 0.361, 0.635, 0.680; all P<0.01). ②After adjustment for age, body mass index, systolic blood pressure, course of hypertension, antihypertensive and antispasmodic treatments, gestational diabetes mellitus, subclinical hypothyroidism, LVEF, multiple linear regression analysis showed that SpI and LVMI were independent predictors of SDI (β=0.228, 0.319; all P<0.01). ③Binary Logistic regression analysis showed that SpI and LVMI were independently correlated with left ventricular systolic dyssynchrony [ OR(95% CI)=1.288(1.039-1.598), 1.102(1.019-1.192); all P<0.05]. Conclusions:Left ventricular remodeling in patients with SPE leads to the decrease of left ventricular systolic synchronization, which can reflect subclinical myocardial dysfunction early. Full volume imaging technology can accurately evaluate left ventricular systolic synchronization in patients with SPE.

Objective To evaluate the clinical efficacy of Yangxue-Pinggan decoction on intractable headache. Methods A total of 66 patients with intractable headache who met the inclusion criteria were randomly divided into two groups by random number table method, 33 in each group. The control group was given flunarizine hydrochloride capsule orally, while the treatment group was given professor Guan Youbo's Yangxue-Pinggan decoction. Both groups were treated for 4 weeks. The improvement rates of headache were observed. The headache attacks, the degree of headache, the duration of headache and the accompanying symptoms were scored, and the clinical efficacy was evaluated. Results The total effective rate was 97.0％ (32/33) in the treatment group and 63.6％ (21/33) in the control group, which there was significant difference between the two groups (χ2=11.591, P=0.001). After treatment, the scores of the headache attacks, the degree of headache, the duration of headache and the accompanying symptoms in the treatment group were significantly lower than those in the control group (t=17.689, 12.523, 26.907, 25.569, P<0.001). Conclusions The Yangxue-Pinggan decoction can obviously improve the clinical symptoms of intractable headache, relieve the pain degree and reduce the number of attacks, and its clinical efficacy is better than oral flunarizine hydrochloride capsule.

Objective In order to verify the validation of the industry standard WS/T 405‐2012 about adult blood cell analysis reference range ,and ensuring their clinical application .Methods According to Clinical and Laboratory Standards Institute(CLSI) C28‐A3 recommendation method ,40 health reference individuals were enrolled in the study whose blood samples were collected ,de‐tected and analyzed .Results The blood cell analysis indicators involved in the validation included WBC ,RBC ,hemoglobin(HGB) , hematocrit(HCT) ,mean corpuscular volume(MCV) ,mean corpuscular hemoglobin(MCH) ,mean corpuscular hemoglobin concen‐tration(MCHC) ,platelet(PLT ) ,etc .The probability of all results of selected 40 reference individuals beyond the WS/T 405‐2012 blood cell analysis reference interval were no more than 10% (value 90% or higher) .Conclusion The WS/T 405‐2012 blood cell a‐nalysis reference range is suitable for the laboratory .A perfective verification system should be established to ensure its application .

Objective To investigate the effects of Triptolide on apoptosis of cultured rat mesangial cells treated by TGF-β1 and the role of Smac in this process. Methods The mesangial cells were pre-treated with different concentrations of Triptolide for 24 hours, then stimulated with TGF-β1 for 24 hours. Apoptotic cells were detected by TUNEL assay. Smac transcription level was determined by Real time-PCR analyses. Smac expression level was assessed using Western blot anal-yses. Localization of Smac was shown by confocal fluorescence microscopy. Results Compared with control group, TGF-β1 inhibited apoptosis and Smac transcription and expression in rat mesangial cells. By contrast, Triptolide promoted mesangial cells apoptosis. In Triptolide groups, Smac mRNA and protein levels were up-regulated. Additionally, in normal and TGF-β1 groups Smac protein was mainly localized in mitochondriawhile in Triptolide groupit was mainly localized in cytoplasm and nucleus with increased fluorescence intensity. Conclusion Triptolide could promote the effect that TGF-β1 inhibited apop-tosis of mesangial cells, through both up-regulation the expression of Smac and stimulating it translocation from mitochon-dria to cytoplasm and nucleus.

Objective To evaluate the impacts of health management on quality of life of patients with chronic obstructive pulmonary disease (COPD).Methods Ninety COPD in-or out-patients were assigned to two groups according to visit date.The control group was treated with conventional therapy,and the observation group obtained conventional therapy + standard health management for 6 months.Cigarette smoking,6 MWT/m and The St George's Respiratory Questionnaire (SGRQ) were evaluated before and after the intervention.Results At 6 months,the ratio of current cigarette smoking of the observation group was much lower than that at baseline (x2=4.464,P＜0.05),6 MWD/m was significantly increased (337.2±82.6 vs 372.0±76.3,t=-7.14,P=0.00),and the scores of respiratory symptoms,limitation of motion and influence of disease and total score of SGRQ were significantly reduced (t values were 6.15,5.18,4.70 and 5.07,respectively; all P＜0.05).Conclusion Standard health management could decrease the rate of current cigarette smoking and improve exercise tolerance and the quality of life of COPD patients.