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Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative changes of spinal structure that increase the risk of low back pain. Apoptosis in nucleus pulposus (NP) can aggravate IVD degeneration, and increasing studies have shown that interventions targeting NP cell apoptosis can ameliorate IVD degeneration, exhibiting their potential for use as therapeutic strategies. Recent data have shown that advanced glycation end products (AGEs) accumulate in NP tissues in parallel with the progression of IVD degeneration and form a microenvironment of oxidative stress. This study examined whether AGEs accumulation aggravates NP cell apoptosis and IVD degeneration, and explored the mechanisms underlying these effects. We observed that the viability and proliferation of human NP cells were significantly suppressed by AGEs treatment, mainly due to apoptosis. Furthermore, activation of the mitochondrial apoptosis pathway was detected after AGEs treatment. In addition, the molecular data showed that AGEs could significantly aggravate the generation of mitochondrial reactive oxygen species and prolonged activation of the mitochondrial permeability transition pore, as well as the increased level of Bax protein and decreased level of Bcl-2 protein in mitochondria. These effects could be reduced by antioxidant (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (MitoTEMPO) and Visomitin (SKQ1). Importantly, we identified that impairment of Sirtuin3 (SIRT3) function and the mitochondrial antioxidant network were vital mechanisms in AGEs-induced oxidative stress and secondary human NP cell apoptosis. Finally, based on findings that nicotinamide mononucleotide (NMN) could restore SIRT3 function and rescue human NP cell apoptosis through adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor-γ coactivator 1α (AMPK-PGC-1α) pathway in vitro, we confirmed its protective effect on AGEs-induced IVD degeneration in vivo. In conclusion, our data demonstrate that SIRT3 protects against AGEs-induced human NP cell apoptosis and IVD degeneration. Targeting SIRT3 to improve mitochondrial redox homeostasis may represent a potential therapeutic strategy for attenuating AGEs-associated IVD degeneration.

Study Design. A systematic review and meta-analysis. Objective. The objective of this study was to investigate the incidence of surgical site infection (SSI) in patients following spine surgery and the rate of microorganisms in these cases. Summary of Background Data. Many studies have investigated the incidence and risk factors of SSI following spinal surgery, whereas no meta-analysis studies have been conducted regarding the comprehensive epidemiological incidence of SSI after spine surgery. Methods. We searched the PubMed, Embase, and Cochrane Library databases for relevant studies that reported the incidence of SSI after spine surgery, and manually screened reference lists for additional studies. Relevant incidence estimates were calculated. Subgroup analysis, sensitivity analysis, and publication bias assessment were also performed. Results. Our meta-analysis included 27 studies, with 603 SSI cases in 22,475 patients. The pooled SSI incidence was 3.1%. Subgroup analysis revealed that the incidence of superficial SSI was 1.4% and the incidence of deep SSI was 1.7%. Highest incidence (13.0%) was found in patients with neuromuscular scoliosis among the different indications. The incidences of SSI in cervical, thoracic, and lumbar spine were 3.4%, 3.7%, and 2.7%, respectively. Compared with posterior approach surgery (5.0%), anterior approach showed a lower incidence (2.3%) of SSI. Instrumented surgery had a higher incidence of SSI than noninstrumented surgery (4.4% vs. 1.4%). Patients with minimally invasive surgery (1.5%) had a lower SSI incidence than open surgery (3.8%). Lower incidence of SSI was found when vancomycin powder was applied locally during the surgery (1.9%) compared with those not used (4.8%). In addition, the rates of Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant Staphylococci in microbiological culture results were 37.9%, 22.7%, and 23.1%, respectively. Conclusion. The pooled incidence of SSI following spine surgery was 3.1%. These figures may be useful in the estimation of the probability of SSI following spine surgery. Level of Evidence: 3

, a novel coronavirus that is related to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in phylogenetic distance was identified. 1 This virus, which was later designated as SARS-CoV-2, also causes acute respiratory disease syndrome (ARDS) termed coronavirus disease 2019 (COVID-19), which was declared as a pandemic by the World Health Organization in March 2020. Although the majority of patients of COVID-19 show moderate symptoms such as dry cough and fatigue, up to 20% cases develop severe symptoms characterized as ARDS, a clinical pulmonary phenomenon marked by the development of bilateral infiltrates and hypoxemia. 2 The median incubation period of SARS-CoV-2 infection is~4-5 days before symptom onset, and the majority of symptomatic patients develop symptoms within 11.5 days. Within 5-6 days of symptom onset, SARS-CoV-2 viral load reaches its peak, which is much earlier than SARS-CoV. 3 Severe COVID-19 cases progress to ARDS with hypoxemia around 8-12 days after symptom onset. 2 Although various independent factors such as older age and existing diseases contribute to mortality, the majority of fatal patients die of complications such as ARDS, myocardial injury, acute kidney injury, and sepsis. 2,3 The pathogenesis of COVID-19 has been heavily investigated in the past months. Pathophysiology in COVID-19 is characterized by diffuse alveolar damage, focal reactive hyperplasia of pneumocytes, inflammatory cellular infiltration, vasculitis, hypercoagulability, neutrophilia, and lymphopenia. 4 Studies have suggested that hyper-inflammation is linked to more severe disease of COVID-19, which is characterized by a cytokine releasing syndrome (CRS). 3,5 It has been reported that some inflammatory cytokines (such as IL-6, IL-10, and TNF-α) and chemokines (such as CXCL10/ IP-10, CCL2/MCP-1, and CCL3/MIP-1α) are upregulated in COVID-19 patients. 2 However, these studies are limited by the small sample size, narrowed cytokine and chemokine spectrum, and absence of temporal kinetic analysis of these factors with disease progression. Currently, limited information is available on host factors and biomarkers affecting individual outcomes in COVID-19. Identification of host plasma factors that are correlated to COVID-19 progression may provide potential biomarkers and targets for developing therapeutics. To systematically investigate the kinetic changes of plasma levels of cytokines, chemokines and growth factors (CCGFs) over the disease courses in COVID-19 patients as well as the correlations between the CCGF profiles and disease severity, we measured levels of 48 CCGFs in plasma of mild, severe and fatal COVID-19 patients collected at different stages of disease courses. We collected sera from 6 fatal, 7 severe, and 10 mild patients at day 1, 5, 10, and 14 after diagnosis. One sample was collected from each of the 4 healthy donors. We measured the levels of