Comparison of Delta Spinal Endoscopy and Bilateral Laminotomy for Short-term Patient Outcomes in Degenerative Lumbar Spinal Stenosis.

This prospective randomised controlled trial aimed to compare the clinical efficacy of Delta spinal endoscopy with bilateral laminotomy for degenerative lumbar spinal stenosis (DLSS). Eighty patients with DLSS were randomly assigned to two groups: 40 treatments by Delta spinal endoscopy named (A) and 40 treatments by bilateral laminotomy named (A). Patients were followed up for one year. The incision length, intraoperative bleeding, and hospitalisation time were lower in group A than in B (p <0.01); however, the operation time in group B was lower than in A (p <0.05). The VAS and ODI in both groups improved significantly after surgery, compared with the results before the surgery. The VAS and ODI in group A after surgery were lower than in B, but only for one week after the surgery, (p <0.05). The excellent rate of modified MacNab criteria was not statistically significant between groups A and B (p >0.05). Overall, Delta spinal endoscopy can effectively manage DLSS with faster patient recovery. Key Words: Delta spinal endoscopy, Spinal stenosis, Minimally invasive, Bilateral laminotomy.

Trastuzumab-induced cardiomyopathy via ferroptosis-mediated mitochondrial dysfunction.

Trastuzumab (TRZ) is a first-line chemotherapeutic agent for HER-2 (ErbB2)-positive breast cancer. Unfortunately, its clinical use is limited due to its cardiotoxicity, referred to as TRZ-induced cardiotoxicity (TIC). However, the exact molecular mechanisms underlying the development of TIC remain unclear. Iron and lipid metabolism and redox reactions participate in the development of ferroptosis. Here, we show that ferroptosis-mediated mitochondrial dysfunction is involved in TIC in vivo and in vitro. We first established TIC models with BALB/c mice or neonatal rat cardiomyocytes and confirmed cardiomyopathy with echocardiography and inhibition of cell viability with a cell counting kit-8 examination, respectively. We showed that TRZ downregulated glutathione peroxidase 4 (GPx4) and elevated lipid peroxidation by-products, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), by inactivating the ErbB2/PI3K/AKT/Nrf2 signalling pathway. Additionally, upregulated mitochondrial 4-HNE binds to voltage-dependent anion channel 1 (VDAC1), increases VDAC1 oligomerization, and subsequently induces mitochondrial dysfunction, as evidenced by mitochondrial permeability transition pore (mPTP) opening and decreased mitochondrial membrane potential (MMP) and ATP levels. Concomitantly, TRZ affected the mitochondrial levels of GSH/GSSG and iron ions and the stability of mitoGPx4. Ferroptosis inhibitors, such as ferrostatin-1 (Fer-1) or the iron chelator deferoxamine (DFO), ameliorate TRZ-induced cardiomyopathy. Overexpression of mitoGPx4 also suppressed mitochondrial lipid peroxidation and prevented TRZ-induced ferroptosis. Our study strongly suggests that targeting ferroptosis-mediated mitochondrial dysfunction is a potential cardioprotective strategy.

Short-Term Patient Outcomes Using the Interlaminar Endoscopic Surgical System Ilessys® Delta System versus Bilateral Laminotomy: A Single-Center Study of 80 Patients with Degenerative Lumbar Spinal Stenosis.

BACKGROUND This study from a single center aimed to compare short-term patient outcomes from the Interlaminar Endoscopic Surgical System iLESSYS® Delta system vs bilateral laminotomy in 80 patients with degenerative lumbar spinal stenosis (DLSS). MATERIAL AND METHODS We selected 80 patients with DLSS for the study. Of these, 40 were treated with the iLESSYS® Delta system and 40 were treated with bilateral laminotomy. We followed these patients for 1 year. We recorded and compared data on incision length, operation time and intraoperative blood loss, hospitalization time, postoperative complications, the visual analog scale (VAS), and Oswestry Disability Index (ODI) before, 1 week, 3 months, 6 months, and 12 months after surgery, and the Modified Macnab evaluation criteria. RESULTS The incision length, intraoperative blood loss, and hospitalization time were significantly better in group A than in group B (P<0.05); however, the operation time in group B was shorter than that in group A, and the differences were statistically significant (P<0.05). The VAS and ODI in both groups improved significantly after surgery compared with before the operation. The VAS and ODI in group A patients after surgery were lower than those in group B, and only at 1 week after surgery,(P<0.05). The excellent rate of modified MacNab criteria was not statistically significant between groups A and B (P>0.05). CONCLUSIONS Use of the Interlaminar Endoscopic Surgical System iLESSYS® Delta system can effectively manage DLSS and speed patient recovery.

Cell death regulation in myocardial toxicity induced by antineoplastic drugs.

Homeostatic regulation of cardiomyocytes plays a critical role in maintaining normal physiological activity of cardiac tissue. Severe cardiotoxicity can lead to heart disease, including but not limited to arrhythmias, myocardial infarction and cardiac hypertrophy. In recent years, significant progress has been made in developing new therapies for cancer that have dramatically changed the treatment of several malignancies and continue to improve patient survival, but can also lead to serious cardiac adverse effects. Mitochondria are key organelles that maintain homeostasis in myocardial tissue and have been extensively involved in various cardiovascular disease episodes, including ischemic cardiomyopathy, heart failure and stroke. Several studies support that mitochondrial targeting is a major determinant of the cardiotoxic effects triggered by chemotherapeutic agents increasingly used in solid and hematologic tumors. This antineoplastic therapy-induced mitochondrial toxicity is due to different mechanisms, usually altering the mitochondrial respiratory chain, energy production and mitochondrial kinetics, or inducing mitochondrial oxidative/nitrosative stress, ultimately leading to cell death. This review focuses on recent advances in forms of cardiac cell death and related mechanisms of antineoplastic drug-induced cardiotoxicity, including autophagy, ferroptosis, apoptosis, pyroptosis, and necroptosis, explores and evaluates key proteins involved in cardiac cell death signaling, and presents recent advances in cardioprotective strategies for this disease. It aims to provide theoretical basis and targets for the prevention and treatment of pharmacological cardiotoxicity in clinical settings.

Melatonin inhibits atherosclerosis progression via galectin-3 downregulation to enhance autophagy and inhibit inflammation.

Autophagy deficiency in macrophages exacerbates inflammation in atherosclerosis (AS), and recently, galectin-3 (Gal-3) has been implicated as a critical promoter of inflammation in AS. Further, melatonin (Mel) exerts an autophagy-promoting effect in many chronic inflammatory diseases. In this study, we aimed to investigate whether Mel inhibits AS progression by downregulating Gal-3 to enhance autophagy and inhibit inflammation. Thus, we performed in vivo and in vitro experiments using high-fat diet (HFD)-fed ApoE-/-  mice and THP-1 macrophages, respectively. Smart-seq of AS plaque macrophages revealed that the differentially expressed genes (DEGs) downregulated by Mel were enriched in immune-related processes, and changes in inflammation status were confirmed based on lower levels of proinflammatory factors in Mel-treated HFD-fed ApoE-/-  mice and THP-1 macrophages. Further, via transcriptome-based multiscale network pharmacology platform (TMNP), the upstream target genes of the smart-seq DEGs were identified, and Gal-3 showed a high score. Gal-3 was downregulated both in vivo and in vitro by Mel treatment. Besides, the enrichment of the target genes predicted via the TMNP method indicated that autophagy considerably affected the DEGs. Mel treatment as well as Gal-3 knockdown downregulated most inflammatory response-related proteins could attribute to enhancing autophagy. Mechanistically, Mel treatment inhibited Gal-3 leading to lowering the activity of the nuclear transcription factor-kappa B (NF-κB) pathway, and promoting the nuclear localization of transcription factor EB (TFEB). However, increased secretion of Gal-3 activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway and impaired autophagy via binding to CD98. Thus, Mel promoted autophagy and restrained inflammation by downregulating Gal-3, implying that it holds promise as a treatment for AS.

Preparation of three dimensional bimetallic Cu-Ni/NiF electrodes for efficient electrochemical removal of nitrate nitrogen.

It still remains a hotspot and great challenge to efficiently remove the nitrate nitrogen from high salt wastewater. Herein, a novel three dimensional porous bimetallic copper-nickel alloy electrode was fabricated with Ni foam (NiF) as substrate. The physicochemical and electrochemical characterization results showed Cu-Ni/NiF electrode possessed the smaller particle size (0.3-1.0 µm) and electrode film resistance comparing with Ni/NiF and Cu/NiF electrodes. Besides, higher double layer capacitance (Cdl) for Cu-Ni/NiF electrode indicated more electrochemical active sites could be used in the electrochemical nitrate nitrogen (NO3--N) removal. The electrochemical experiments showed the Cu-Ni/NiF electrode had the optimal NO3--N reduction ability and almost 100% NO3--N removal could be achieved with 30 min. All NO3--N removal processes were in accord with the pseudo-first-order reaction kinetics completely. The gaseous nitrogen selectivity for Cu-Ni/NiF electrode could reach 80.9% within 300 min. Stability assessment experiments indicated the Cu-Ni/NiF electrode all kept an excellent stability with Na2SO4 or NaCl electrolyte and the Cl- addition could significantly improve the gaseous nitrogen selectivity. Finally, a possible removal mechanism of NO3--N was proposed. This work offered a direction for designing non-noble bimetallic electrodes for nitrate removal.