Background The paraspinal and psoas muscles have been considered to be essentially important for stabilizing the spinal column, and the muscle degeneration was found to exist in degenerative spinal kyphosis (DSK) patients. However, it is still not clear the relationship between muscle degeneration and spinal-pelvic alignment. The purpose of this study was to determine the correlations between the individual muscle degeneration at each lumbar spinal level and spinal-pelvic parameters in DSK patients. Methods The imaging data of 32 patients with DSK were retrospectively analyzed. The fat infiltration (FI) and relative cross-sectional area of muscle (RCSA) were quantitatively measured for multifidus (MF), erector spinae (ES) and psoas (PS) at each spinal level from L1/2 to L5/S1. The correlations were analyzed between RCSA and the sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). Results The FI of MF and ES at L3/4, L4/5 and L5/S1 were higher than that at L1/2 and L2/3. The FI of PS at L4/5 and L5/S1 were lower than that of L1/2, L2/3 and L3/4. The RCSA of ES and PS from L1/2 to L5/S1 gradually increased, whereas the RCSA of ES from L1/2 to S5/S1 gradually decreased. The RCSA of MF at the L1/2 level was negatively correlated SVA (r = − 0.397,p = 0.024); the RCSA at L3/4, L4/5 and L5/S1 levels were negatively correlated with TK (r = − 0.364, p = 0.04; r = − 0.38, p = 0.032; r = − 0.432, p = 0.014); the RCSA at L4/5 level was positively correlated with LL (r = 0.528, p = 0.002). The RCSA of ES at L3/4 and L4/5 levels were positively correlated with PI (r = 0.377, p = 0.037) and SS (r = 0.420, p = 0.019). Conclusions FI of MF and ES at lower lumbar level is higher than that at upper level, but FI of PS at upper lumbar level is higher than that at lower level. MF and ES have different roles for maintaining the sagittal spinal-pelvic balance.

Graphical Abstract Highlights d Secreted PKM2 is a potential serum biomarker for diagnosing lung cancer d Secreted PKM2 promotes lung cancer progression d Integrin b1 functions as a receptor for secreted PKM2 d Targeting secreted PKM2 and integrin b1 can attenuate lung cancer metastasis SUMMARYCancer cell-derived secretomes have been documented to play critical roles in cancer progression. Intriguingly, alternative extracellular roles of intracellular proteins are involved in various steps of tumor progression, which can offer strategies to fight cancer. Herein, we identify lung cancer progression-associated secretome signatures using mass spectrometry analysis. Among them, PKM2 is verified to be highly expressed and secreted in lung cancer cells and clinical samples. Functional analyses demonstrates that secreted PKM2 facilitates tumor metastasis. Furthermore, mass spectrometry analysis and functional validation identify integrin b1 as a receptor of secreted PKM2. Mechanistically, secreted PKM2 directly bound to integrin b1 and subsequently activated the FAK/SRC/ERK axis to promote tumor metastasis. Collectively, our findings suggest that PKM2 is a potential serum biomarker for diagnosing lung cancer and that targeting the secreted PKM2-integrin b1 axis can inhibit lung cancer development, which provides evidence of a potential therapeutic strategy in lung cancer.

BackgroundAnterior cervical discectomy and fusion (ACDF) has been widely used in cervical spondylosis, but adjacent segment degeneration/disease (ASD) was inevitable. Cervical total disc replacement (TDR) could reduce the stress of adjacent segments and retard ASD in theory, but the superiority has not been determined yet. This analysis aimed that whether TDR was superior to ACDF for decreasing adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis).MethodsA meta-analysis was performed according to the guidelines of the Cochrane Collaboration with PubMed, EMBASE, Cochrane Library and CBM (China Biological Medicine) databases. It included randomized controlled trials (RCTs) that reported ASDeg, ASDis, and reoperation on adjacent segments after TDR and ACDF. Two investigators independently selected trials, assessed methodological quality, and evaluated the quality of this meta-analysis using the grades of recommendation, assessment, development, and evaluation (GRADE) approach.ResultsEleven studies with 2632 patients were included in the meta-analysis. The overall rate of ASD in TDR group was lower than ACDF group (OR = 0.6; 95% CI [0.38, 0.73]; P < 0.00001). Both the incidence of ASDeg and the reoperation rate were statistically lower in the TDR group than in the ACDF group (OR = 0.58, P < 0.00001; OR = 0.52, P = 0.01, respectively). Subgroup analysis was performed according to the follow-up time and trial site; the rate of ASDeg was lower in patients underwent TDR no matter the follow-up time, and TDR tended to increase the superiority across time. The rate of ASDeg was also lower with TDR both in the USA and China (P < 0.0001, P = 0.03, respectively). But the cost-effectiveness result might be prone to neither of the two surgery approaches. According to GRADE, the overall quality of this meta-analysis was moderate.ConclusionsTDR decreased the rates of ASDeg and reoperation compared with that of ACDF, and the superiority may become more apparent over time. We cautiously and slightly suggest adopting TDR according to the GRADE but may not believe it excessively.Electronic supplementary materialThe online version of this article (10.1186/s13018-018-0940-9) contains supplementary material, which is available to authorized users.

Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase–CCAAT/enhancer-binding protein-homologous protein (PERK–CHOP) signaling, thus inducing apoptosis. Furthermore, we found that the first two EF-hand calcium-binding motifs of RCN1 specifically interact with inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) on loop 3 of its ER luminal domain and inhibit ER calcium release and apoptosis. Together, these data indicate that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis.

Disturbance of endoplasmic reticulum (ER) homeostasis causes ER stress and leads to activation of the unfolded protein response, which reduces the stress and promotes cell survival at the early stage of stress, or triggers cell death and apoptosis when homeostasis is not restored under prolonged ER stress. Here, we report that Cab45S, a member of the CREC family, inhibits ER stress-induced apoptosis. Depletion of Cab45S increases inositol-requiring kinase 1 (IRE1) activity, thus producing more spliced forms of X-box-binding protein 1 mRNA at the early stage of stress and leads to phosphorylation of c-Jun N-terminal kinase, which finally induces apoptosis. Furthermore, we find that Cab45S specifically interacts with 78-kDa glucose-regulated protein/immunoglobulin heavy chain binding protein (GRP78/BiP) on its nucleotide-binding domain. Cab45S enhances GRP78/BiP protein level and stabilizes the interaction of GRP78/BiP with IRE1 to inhibit ER stress-induced IRE1 activation and apoptosis. Together, Cab45S, a novel regulator of GRP78/BiP, suppresses ER stress-induced IRE1 activation and apoptosis by binding to and elevating GRP78/BiP, and has a role in the inhibition of ER stress-induced apoptosis.