OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

BACKGROUND: Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. METHODS: A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. RESULTS: At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046). CONCLUSIONS For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Humans ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Coronary Occlusion/surgery* ; Prognosis ; Angina, Unstable/surgery* ; Chronic Disease ; Risk Factors

Objective : To explore the influence and mechanism of different types of proteins on the corrosion resistance of alloy to provide a reference for the safe application and surface modification of nickel-titanium (Ni-Ti) and stainless steel bow wires in the clinic. Methods: The effects of fibrinogen, IgG and mucin on the electrochemical corrosion resistance of Ni-Ti and stainless steel arch wires were tested by the potentiodynamic polarization method, and the repair ability of passive films on surfaces treated with the three proteins were tested by the cyclic polarization method. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to determine the types of corrosion products, and the surface morphology after corrosion was analyzed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Results : The addition of fibrinogen, IgG or mucin to an alloy has different effects on its corrosion resistance. Adding protein can reduce the corrosion resistance of stainless steel alloys and slow the corrosion process of Ni-Ti alloys. The addition of mucin can improve the corrosion resistance of Ni-Ti alloy and the repair ability of passive film. Compared with mucin and IgG, fibrinogen can reduce the pitting resistance of Ni-Ti and stainless steel alloys. Conclusion Different types of proteins interact differently with the arch wire, form different deposition morphologies on the surface, and participate differently in the corrosion process of the alloy.

Objective To establish a qualitative and quantitative determination of glyphosate in serum using ultraviolet spectro-photometry(UV) to provide basis for clinical diagnosing and treating glyphosate poisoning .Methods The mixture of 0 .5 mL serum and 0 .2 mL 10% methanol solution of perchloric acid was shocked and centrifuged with 10 000 r/min for 5 min .A nitrosyla-tion reaction conducted on supernatant and 50 μL serum nitrosylation liquid was detected by UV scanning .Results The results of serum theophylline absorption maxima was(243 ± l) nm and the concentration of 10 .0-60 .0 μg/mL range linear regression equa-tion was Y=0 .0173 8X+0 .036 3(r= 0 .999 8) .The recovery rate was from 85 .5% to 102 .4% and the relative standard deviation (RSD) was from 3 .50% to 4 .90% .The intra-day and inter-day RSD were 3 .79% -5 .10% and 3 .88% -4 .55% .The minimum de-tectable concentration was 5μg/mL .Conclusion This method is simple ,rapid and accurate results for detecting glyphosate poison-ing .

Objective To evaluate the role and efficacy of preventing bone mineral loss in patients with endometriosis treated by gonadotrophin-releasing hormone analogues (GnRH-a) combined with addback therapy.Methods Prospective,randomized controlled studies of the use of GnRHa with add-back therapy in treatment of endometriosis were enrolled in this study from Medline,Embase,Cochrane library,China National Knowledge Internet (CNKI),Chinese Biological Medicine Disk (CBM) and Data Base of Wanfang.After quality assessment and data extraction,meta-analysis were conducted in the change of BMD,reproductive hormone (E2) and visual pain score (VAS) by Stata 11.0 software.Results A total of 785patients from 13 randomized controlled trail (RCT) studies enrolled in this study after exclude no following up,poor quality and repeat published studies.377 patients were in group of GnRH-a with add-back treatment and 408 patients were in group of GnRna alone.The findinds were showed in meta-analysis:(1) there was a significant difference in percentage change of bone mineral density (BMD) between two groups,the addback therapy was more effective in prevention of bone loss which was (SMD =0.223,95％ CI:0.003 to 0.443,P =0.047).(2) There was no significant difference in the level of reproductive hormone between two groups (SMD =-0.053,95％ CI:-0.479 to 0.373,P =0.807).(3) There was also no significant difference in the visual pain score between the two groups (SMD =-0.157,95％ CI:-0.474 to 0.160,P=0.332).Conclusions GnRH-a with add-back therapy have been shown to be more effective in preventing loss of BMD than GnRH-a treatment alone.However,the long term effect of preventing BMD should be studied.