Clinical outcomes of S2 Alar-Iliac screw technique in the treatment of severe spinal sagittal imbalance: a retrospective 2-year follow-up study

Background: The treatment of adult spinal deformity (ASD) remains a significant challenge, especially in elderly patients. This study aimed to evaluate the outcomes of the S2AI screw technique in the treatment of severe spinal sagittal imbalance with a minimum 2-year follow-up.Methods: From January 2015 to December 2018, 23 patients with severe degenerative thoracolumbar kyphosis who underwent placement of S2AI screws for long segment fusion were retrospectively reviewed. Patients were divided into group A (no mechanical complications, 13 cases) and group B (with mechanical complications, 10 cases) according to the occurrence of mechanical complications at the last follow-up. Radiographic parameters were compared between groups preoperatively, 1 month postoperatively and at the last follow-up. Risk factors for mechanical complications were analyzed.Results: The incidence of mechanical complications was 43.5% and the revision rate was 17.4%. At 1 month postoperatively, sagittal correction was better in group A than in group B (p<0.05). The area under the curve for predicting mechanical complications of sacral slope (SS), lumbar lordosis (LL), PI (pelvic incidence)-LL at 1 month postoperatively were 0.762 (p=0.035), 0.896 (p=0.001) and 0.754 (p=0.041) respectively and the best cut-off values were 24.1°, 32.8°and 12.0°. The sagittal correction of both groups was partially lost at the last follow-up.Conclusions: A high incidence of mechanical complications was observed in long-segment corrective surgery with the S2AI screw technique for severe spinal sagittal imbalance. Inadequate sagittal correction is a risk factor for the development of mechanical complications.

The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity

T regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that glutathione peroxidase 4 (Gpx4) prevents Treg cells from lipid peroxidation and ferroptosis in regulating immune homeostasis and antitumor immunity. Treg-specific deletion of Gpx4 impairs immune homeostasis without substantially affecting survival of Treg cells at steady state. Loss of Gpx4 results in excessive accumulation of lipid peroxides and ferroptosis of Treg cells upon T cell receptor (TCR)/CD28 co-stimulation. Neutralization of lipid peroxides and blockade of iron availability rescue ferroptosis of Gpx4-deficient Treg cells. Moreover, Gpx4-deficient Treg cells elevate generation of mitochondrial superoxide and production of interleukin-1β (IL-1β) that facilitates T helper 17 (TH17) responses. Furthermore, Treg-specific ablation of Gpx4 represses tumor growth and concomitantly potentiates antitumor immunity. Our studies establish a crucial role for Gpx4 in protecting activated Treg cells from lipid peroxidation and ferroptosis and offer a potential therapeutic strategy to improve cancer treatment

The Effects of Warfarin on the Pharmacokinetics of Senkyunolide I in a Rat Model of Biliary Drainage After Administration of Chuanxiong

The aim of this study was to elucidate the effects of warfarin on senkyunolide I in a rat model of biliary drainage after oral administration Chuanxiong extract based on pharmacokinetics. Thirty-two rats were randomly divided into four groups: CN, healthy rats after a single administration of Chuanxiong; CO, rats with biliary drainage after a single administration of Chuanxiong; WCN, healthy rats after the administration of Chuanxiong and warfarin; WCO, rats with biliary drainage after the administration of Chuanxiong and warfarin. A series of blood samples were collected at different time points before and after oral administration. An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for quantification of the main components of Chuanxiong and methyclothiazide (internal standard) have been established. The validated method was successfully applied to a comparative pharmacokinetics study. After calculated by the DAS 2.1.1 software, the pharmacokinetics parameters of senkyunolide I showed a significant difference between the CN and CO groups, the AUC0−t, and Cmax of CO group increased by 5.45, 4.02 folds, respectively. There was a significant difference between the WCO and WCN groups, the Tmax of WCO group prolonged 67%; compared to the CN group, the AUC0−t, and Cmax of WCN group raised 4.84, 3.49 folds, respectively; the Tmax and Cmax between the CO and WCO groups also showed a significant difference. The drug warfarin significantly affected the senkyunolide I disposition, which partly due to its enterohepatic circulation process in rat plasma after oral administration of Chuanxiong. The present study highlights an urgent evidence for drug-herb interactions

Transcriptional Repression of CYP3A4 by Increased miR-200a-3p and miR-150-5p Promotes Steatosis in vitro

Hepatic cytochrome P450 enzyme activities correlate with non-alcoholic fatty liver disease (NAFLD) and hepatic steatosis. The decreased activity of CYP3A4, an important drug-metabolizing enzyme, is associated with the progression of NAFLD. CYP3A4 is predicted as a target gene of miR-200a-3p and miR-150-5p by MicroInspector and TargetScan algorithms analyses. Here, we found decreased CYP3A4 and increased miR-200a-3p and miR-150-5p in LO2 cells with free fatty acid (FFA)-induced steatosis. Dual-luciferase assay confirmed that both miR-200a-3p and miR-150-5p targeted the 3′-untranslated region (3′-UTR) of CYP3A4 and that such interaction was abolished by miRNA binding site mutations in 3′-UTR of CYP3A4. Using miR-200a-3p and miR-150-5p mimics and inhibitors, we further confirmed that endogenous CYP3A4 was regulated posttranscriptionally by miR-200a-3p or miR-150-5p. Moreover, miR-200a-3p and miR-150-5p inhibitors attenuated FFA-induced steatosis in LO2 cells, and such effect was dependent on CYP3Y4 expression. These results suggest that miR-200a-3p and miR-150-5p, through directly targeting 3′-UTR of CYP3A4, contribute to the development of FFA-induced steatosis

Role of matrix Metalloproteinases in pituitary adenoma invasion

Abstract Though pituitary adenomas are benign tumors in most cases, a considerable fraction of PAs behave in a malignant-like manner and invade to the adjacent structures in sellar region, especially the cavernous sinuses. Cancer-cell invasion and metastasis remain a great challenge for physicians and surgeons in spite of emerging advances in drug therapy and surgical Treatment. matrix metalloproteinases, as a family of zinc-dependent endopeptidases, have long been known to be associated with tumor invasion and metastasis mainly via breaking down basement membrane in different tissues. Aberrant expression and activation of matrix metalloproteinases have been detected in invasive pituitary adenomas as in malignancy and correlated to tumor invasion. Therefore, matrix metalloproteinases are considered as promising biomarkers for predicting tumor behavior and even drug targets for novel therapeutic strategies. In this review, we give an overview of the expression, function, regulation and clinical prospects of matrix metalloproteinases, especially focusing on the biological network in which matrix metalloproteinases may be abnormally activated in promoting pituitary adenoma invasion