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 summarize the characteristics and nursing experience of patients of transthyretin amyloid polyneuropathy.Methods:A retrospective study was performed in 9 patients with transthyretin amyloid polyneuropathy from different area in china from February 2018 to October 2021 in the Second Affiliated Hospital Zhejiang University School of Medical, summarized nursing points:used list to popularize disease knowledge, improved the nursing skills of rare diseases; did a good job in the safety nursing of sensory motor disorders to prevent pressure sores, scalds, fall, thrombosis and other complications, paid attention to the nursing of autonomic nerve dysfunction, prevented postural hypotension. Observe and prevent heart failure, manage diarrhea and constipation, and applied the guide to personalized urinary tract management;provided genetic counseling services, personalized continuing care and psychological care.Results:During hospitalization, the clinical symptoms of 9 patients were improved to varying degrees, after 3 months of telephone follow-up after discharge, 9 patients had no adverse events such as pressure ulcer and fall.Conclusions:By improving specialized skills, predictive risk management and symptom care, the symptoms of postural hypotension, urinary retention, constipation, diarrhea and other symptoms of transthyretin amyloid polyneuropathy patients can be prevented and improved, and adverse events such as falls and pressure sores can be avoided.

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 investigate the incidence of post-bronchiolitis recurrent wheezing and its risk factors in children. Methods: This study was conducted on patients with bronchiolitis admitted to the Department of Respiratory Disease, Children′s Hospital of Soochow University between November 2016 and March 2017.Nasopharyngeal secretions were taken from all patients and assessed for respiratory pathogens.After discharge, the patients were followed up every 3 months by outpatient visit or telephone call for 1 year. Results: Eighty-nine patients with bronchiolitis were enrolled in this study.Among those 89 patients, respiratory syncytial virus(RSV) infection accounted for 46.1%(41/89 cases), Mycoplasma pneumonia(MP) for 5.6%(5/89 cases), rhinovirus(RV) for 4.5%(4/89 cases), and human bocavirus(hBoV) for 2.2%(2/89 cases). Eighty-three patients were successfully followed up.At the 3, 6, 9, and 12 months of follow-up, the occurrence of wheezing episodes for only once happened in 20 cases(24.1%), 27 cases(32.5%), 35 cases (42.2%), and 38 cases(45.8%), respectively.At 12 months after initial bronchiolitis, the occurrence of wheezing episodes for only once happened in 21 cases(25.3%), 2 episodes of wheezing in 10 cases(12.0%), and 7 cases (8.4%) had more than 3 episodes of wheezing, and 6 cases lost follow-up.The proportion of eczema and milk-protein allergy in post-bronchiolitis recurrent wheezing group was significantly higher than that of the group with not post-bronchiolitis recurrent wheezing patients (χ²=6.219, 4.855, all P<0.05). Logistic regression analysis showed eczema was the independent risk factor for post-bronchiolitis recurrent wheezing(OR=0.189, 95%CI: 0.047-0.765). There were no significant difference in gender, age, premature birth, birth weight, feeding pa-tterns, family history of asthma, pet contact history, severity of disease, course of disease, total immunoglobulin E of serum and the species of virus infected between 2 groups(all P>0.05). Conclusions The incidence of recurrent wheezing among post-bronchiolitis patients is higher during one-year follow-up period.Eczema is the independent risk factor for post-bronchiolitis recurrent wheezing.The specific pathogens and severity of disease have no correlation with post-bronchiolitis wheezing.

Objective To evaluate the left atrial(LA) function in patients with severe preeclampsia ( SPE) by full-volume imaging technology. Methods Forty-two patients of SPE were randomly chosen as SPE group,34 healthy pregnant women were selected as the control group. LA related function parameters including LA maximum volume( LAVmax),LA minimum volume( LAVmin),LA pre-atrium contraction volume(LAVpre),LA reservoir volume(LARV),LA passive emptying volume(LAPEV),LA contraction volume(LACV),LA expansion index(LAEI),LA passive emptying fraction(LAPEF),LA passive emptying fraction( LAAEF ) were separately required by biplane area-length method and full-volume imaging technology in antepartum and postpartum. Results Compared with control group before delivery,the parameters of SPE group before delivery such as LAVmax,LAVmin,LAVpre were higher,LAEI,LAPEF, LAAEF indexed to body surface area(BSA) were lower(all P ＜0.01).Compared with control group before delivery,the parameters of control group after delivery such as LAVmax,LAVmin,LAVpre were lower( all P ＜0.05),LAEI, LAAEF calculated as ratio to BSA were somewhat reduced,LAPEF calculated as ratio to BSA was relatively higher(all P ＞0.05).Compared with SPE group before delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were lower,LAEI,LAPEF,LAAEF indexed to BSA were higher( all P ＜0.01). Compared with control group after delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were still incresed ( all P ＜ 0.05 ), LAEI,LAPEF, LAAEF indexed to BSA were relatively lower( all P ＞0.05). Conclusions Full-volume imaging technology can quantitatively evaluate the LA function. LA reservoir function,conduit function and booster pump function are reduced in SPE before delivery,LA rereservoir function,conduit function and booster pump function are basically recovery in SPE after delivery.

Objective To explore the relationship between serum HBV DNA level , expression of PD-1 on CTL and liver functions in patients with hepatitis B virus cirrhosis. Methods 109 HBV hepatic cirrhosis patients with , HBV DNA positive , HBeAg positive and HLA-A2 positive were divided into two groups according to their HBV DNA levels,52 cases in group A, HBV DNA 2-4 log10 copies/mL, 57cases in group B, HBV DNA 5-7 log10 copies/mL , differences of HBV specific CTL surface PD-1 expressions , HBV specific CTL levels and liver functions were compared between two groups. Results HBV specific CTL surface PD-1 expressions of group A were lower than that of group B (t = 11.101, P < 0.01), HBV specific CTL levels of group A were higher than that of group B (t = 24.424, P < 0.01), ALT of group A were lower than that of group B (t = 2.652, P < 0.01), ALB of group A were higher than that of group B (t = 2.347, P < 0.05). Child-pugh rating, grade C of group A was lower than that of group B (χ2= 4.262,P < 0.05). Conclusions HBV specific CTL surface PD-1 expression levels were higher in those hepatic cirrhosis patients with , high level of serum HBV DNA, and HBV specific CTL levels were lower, liver functions damage were much serious. So, lower HBV DNA levels , lower HBV specific CTL surface PD-1 expression levels and higher HBV specific CTL levels can product relatively good effect of anti-viral treatment.

Objective To investigate the association between the difference of specific cytotoxic lymphocyte (CTL) and liver function of patients with hepatitis B virus (HBV) genotype B and C infections and interleukin (IL)‐7 induced follicular helper T lymphocytes (Tfh) .Methods Sixty‐seven patients with chronic hepatitis B (CHB) hospitalized at Wuxi No .5 People′s Hospital from August 2013 to January 2015 were collected and 30 healthy blood donors were set as healthy control group .The peripheral blood IL‐7 , Tfh ,IL‐21 ,HBV specific‐CTL ,nonspecific CTL ,levels of HBV DNA ,alanine aminotransferase (ALT) and total bilirubin (TBil) were compared between patients with genotype B and C infection ,hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB ,high ALT level and low ALT level .Multivariate regression analysis was performed to determine the factors associated with IL‐7 .The t test was used for quantitative data and chi‐square test was used for categorical data .Results Of the 67 CHB patients with average age of (35 .1 ± 11 .4) ,48 were male and 19 were female;32 were infected with genotype C and 35 were infected with genotype B ;40 were HBeAg‐positive CHB and 27 were HBeAg‐negative CHB ;17 were with high ALT levels and 50 were with low ALT levels .IL‐7 ,Tfh ,IL‐21 and HBV specific‐CTL levels in the peripheral blood of genotype C‐infected patients were (20 .79 ± 4 .82 ) ng/L , (3 .93 ± 0 .82)% ,(24 .77 ± 7 .52) ng/L and (0 .20 ± 0 .04)% ,respectively ,while in genotype B‐infected patients , those were (29 .13 ± 8 .17) ng/L ,(5 .92 ± 1 .92)% ,(39 .94 ± 24 .00) ng/L and (0 .40 ± 0 .06)% , respectively .Levels of IL‐7 , Tfh ,IL‐21 and HBV specific‐CTL in genotype C‐infected patients were significantly lower than those in genotype B‐infected patients (t= 5 .027 ,5 .595 ,3 .553 and 15 .133 , respectively ;all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of genotype C‐infected patients were all significantly higher than those in genotype B infected‐patients (t=4 .899 ,6 .815 ,2 .763 and 4 .899 ,respectively ;all P< 0 .01) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of HBeAg‐positive patients were significantly lower than those in HBeAg‐negative patients (all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of HBeAg‐positive patients were all significantly higher than those in HBeAg‐negative patients (all P<0 .05) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of patients with high ALT levels were all significantly lower than those in patients with low ALT levels (all P<0 .01) .Nonspecific CTL and HBV DNA levels in the peripheral blood of patients with high ALT levels were both significantly higher than those in patients with low ALT levels (both P<0 .01) .HBV DNA ,IL‐21 and nonspecific CTL were all correlated with IL‐7 (all P<0 .01) .Conclusion The differences of HBV specific‐CTL and liver function in CHB patients infected with genotype B and C may be correlated with interleukin‐7 induced Tfhcells.