Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death.

Enhanced glutamine catabolism is one of the main metabolic features of cancer, providing energy and intermediate metabolites for cancer progression. However, the functions of glutamine catabolism in cancer under nutrient deprivation need to be further clarified. Here, we discovered that deacetylation of glutamate dehydrogenase 1 (GLUD1), one of the key enzymes in glutamine catabolism, maintains the survival of lung adenocarcinoma (LUAD) cells under glucose starvation by inhibiting autophagic cell death. We found that glucose starvation increased GLUD1 activity by reducing its acetylation on Lys84 and promoted its active hexamer formation. Besides, deacetylation of GLUD1 induced its cytoplasmic localization, where GLUD1 was ubiquitinated in K63-linkage by TRIM21, leading to the binding of GLUD1 with cytoplasmic glutaminase KGA. These two effects enhanced glutamine metabolism both in mitochondria and cytoplasm, increased the production of alpha-ketoglutarate (α-KG). Meanwhile, cytoplasmic GLUD1 also interacted with p62 and prevented its acetylation, leading to the inhibition of p62 body formation. All these effects blocked autophagic cell death of LUAD cells under glucose starvation. Taken together, our results reveal a novel function of GLUD1 under glucose deprivation in LUAD cells and provide new insights into the functions of glutamine catabolism during cancer progression.

Linear polyubiquitylation of Gli protein regulates its protein stability and facilitates tumor growth in colorectal cancer.

The linear ubiquitin chain assembly complex (LUBAC) mediates the linear ubiquitination of various proteins and is involved in NF-κB signaling and immune regulation. However, the function and mechanism of linear ubiquitination in regulating oncogenic signaling and tumor growth have remained poorly understood. Herein, we identified Gli proteins, key transcription factors in the Hedgehog (Hh) signaling pathway, as novel substrates of LUBAC. Linear ubiquitination stabilizes Gli proteins, leading to the noncanonical activation of Hh signaling in CRC cells. Furthermore, LUBAC facilitates tumor growth in CRC cells. Additionally, elevated expression of LUBAC components in CRC tissues was observed, and higher expression levels of these components correlated with poor prognosis in CRC patients. Interestingly, inhibition of LUBAC using either a small molecule agonist or RNA silencing specifically suppressed cell growth in CRC cells but had no effect on normal intestinal cells. Taken together, aberrant expression of LUBAC components activates Hh signaling noncanonically by mediating linear ubiquitination, promoting tumor growth in CRC, demonstrating the novel function of linear ubiquitination in regulating the protein stability of its substrates and highlighting the potential of targeting LUBAC as a therapeutic strategy in CRC.

Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering.

Intervertebral disc degeneration (IVDD) stands as the foremost contributor to low back pain (LBP), imposing a substantial weight on the world economy. Traditional treatment modalities encompass both conservative approaches and surgical interventions; however, the former falls short in halting IVDD progression, while the latter carries inherent risks. Hence, the quest for an efficacious method to reverse IVDD onset is paramount. Biomaterial delivery systems, exemplified by hydrogels, microspheres, and microneedles, renowned for their exceptional biocompatibility, biodegradability, biological efficacy, and mechanical attributes, have found widespread application in bone, cartilage, and various tissue engineering endeavors. Consequently, IVD tissue engineering has emerged as a burgeoning field of interest. This paper succinctly introduces the intervertebral disc (IVD) structure and the pathophysiology of IVDD, meticulously classifies biomaterials for IVD repair, and reviews recent advances in the field. Particularly, the strengths and weaknesses of biomaterials in IVD tissue engineering are emphasized, and potential avenues for future research are suggested.

Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.

PURPOSE: The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth. METHODS: Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting. RESULTS: Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth. CONCLUSION: Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Enhanced Hemostatic and Procoagulant Efficacy of PEG/ZnO Hydrogels: A Novel Approach in Traumatic Hemorrhage Management.

Managing severe bleeding, particularly in soft tissues and visceral injuries, remains a significant challenge in trauma and surgical care. Traditional hemostatic methods often fall short in wet and dynamic environments. This study addresses the critical issue of severe bleeding in soft tissues, proposing an innovative solution using a polyethylene glycol (PEG)-based hydrogel combined with zinc oxide (ZnO). The developed hydrogel forms a dual-network structure through amide bonds and metal ion chelation, resulting in enhanced mechanical properties and adhesion strength. The hydrogel, exhibiting excellent biocompatibility, is designed to release zinc ions, promoting coagulation and accelerating hemostasis. Comprehensive characterization, including gelation time, rheological properties, microstructure analysis, and swelling behavior, demonstrates the superior performance of the PEG/ZnO hydrogel compared to traditional PEG hydrogels. Mechanical tests confirm increased compression strength and adhesive properties, which are crucial for withstanding tissue dynamics. In vitro assessments reveal excellent biocompatibility and enhanced procoagulant ability attributed to ZnO. Moreover, in vivo experiments using rat liver and tail bleeding models demonstrate the remarkable hemostatic performance of the PEG/ZnO hydrogel, showcasing its potential for acute bleeding treatment in both visceral and peripheral scenarios.

DLP-printed GelMA-PMAA scaffold for bone regeneration through endochondral ossification.

Intramembranous ossification (IMO) and endochondral ossification (ECO) are two pathways of bone regeneration. The regeneration of most bone, such as limb bone, trunk bone, and skull base bone, mainly occurs in the form of endochondral ossification, which has also become one of the effective ways for bone tissue engineering. In this work, we prepared a well-structured and biocompatible methacrylated gelatin/polymethacrylic acid (GelMA/PMAA) hydrogel by digital light processing (DLP) printing technology, which could effectively chelate iron ions and continuously activate the hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway to promote the process of endochondral ossification and angiogenesis. The incorporation of PMAA endowed the hydrogel with remarkable viscoelasticity and high efficacy in chelation of iron ions, giving rise to the activation of HIF-1α signaling pathway, improving chondrogenic differentiation in the early stage, and facilitating vascularization in the later stage and bone remodeling. Therefore, the findings have significant implications on DLP printing technology of endochondral osteogenesis induced by the iron-chelating property of biological scaffold, which will provide an effective way in the development of novel bone regeneration.

First-Aid Hydrogel Wound Dressing with Reliable Hemostatic and Antibacterial Capability for Traumatic Injuries.

First-aid for severe traumatic injuries in the battlefield or pre-hospital environment, especially for skin defects or visceral rupture, remains a substantial medical challenge even in the context of the rapidly evolving modern medical technology. Hydrogel-based biomaterials are highly anticipated for excellent biocompatibility and bio-functional designability. Yet, inadequate mechanical and bio-adhesion properties limit their clinical application. To address these challenges, a kind of multifunctional hydrogel wound dressing is developed with the collective multi-crosslinking advantages of dynamic covalent bonds, metal-catechol chelation, and hydrogen bonds. The mussel-inspired design and zinc oxide-enhanced cohesion strategy collaboratively reinforce the hydrogel's bio-adhesion in bloody or humoral environments. The pH-sensitive coordinate Zn2+ -catechol bond and dynamic Schiff base with reversible breakage and reformation equip the hydrogel dressing with excellent self-healing and on-demand removal properties. In vivo evaluation in a rat ventricular perforation model and Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect model reveal excellent hemostatic, antibacterial and pro-healing effectiveness of the hydrogel dressing, demonstrating its great potential in dealing with severe bleeding and infected full-thickness skin wounds.

Application of photocrosslinkable hydrogels based on photolithography 3D bioprinting technology in bone tissue engineering.

Bone tissue engineering (BTE) has been proven to be an effective method for the treatment of bone defects caused by different musculoskeletal disorders. Photocrosslinkable hydrogels (PCHs) with good biocompatibility and biodegradability can significantly promote the migration, proliferation and differentiation of cells and have been widely used in BTE. Moreover, photolithography 3D bioprinting technology can notably help PCHs-based scaffolds possess a biomimetic structure of natural bone, meeting the structural requirements of bone regeneration. Nanomaterials, cells, drugs and cytokines added into bioinks can enable different functionalization strategies for scaffolds to achieve the desired properties required for BTE. In this review, we demonstrate a brief introduction of the advantages of PCHs and photolithography-based 3D bioprinting technology and summarize their applications in BTE. Finally, the challenges and potential future approaches for bone defects are outlined.

3D-Printed GelMA/PEGDA/F127DA Scaffolds for Bone Regeneration.

Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution and gentle printing process. As commonly used bioinks, synthetic polymers such as polyethylene glycol diacrylate (PEGDA) and Pluronic F127 diacrylate (F127DA) have satisfactory printability and mechanical properties but usually lack sufficient adhesion to cells and tissues. Here, a compound BTE scaffold based on PEGDA, F127DA, and gelatin methacrylate (GelMA) was successfully prepared using DLP printing technology. The scaffold not only facilitated the adhesion and proliferation of cells, but also effectively promoted the osteogenic differentiation of mesenchymal stem cells in an osteoinductive environment. Moreover, the bone tissue volume/total tissue volume (BV/TV) of the GelMA/PEGDA/F127DA (GPF) scaffold in vivo was 49.75 ± 8.50%, higher than the value of 37.10 ± 7.27% for the PEGDA/F127DA (PF) scaffold and 20.43 ± 2.08% for the blank group. Therefore, the GPF scaffold prepared using DLP printing technology provides a new approach to the treatment of bone defects.

A Super Tough, Rapidly Biodegradable, Ultrafast Hemostatic Bioglue.

Death happening due to massive hemorrhage has been involved in military conflicts, traffic accidents, and surgical injuries of various human disasters. Achieving rapid and effective hemostasis to save lives is crucial in urgent massive bleeding situations. Herein, a covalent cross-linked AG-PEG glue based on extracellular matrix-like amino-gelatin (AG) and PEG derivatives is developed. The AG-PEG glue gelatinizes fast and exhibits firm and indiscriminate close adhesion with various moist tissues upon being dosed. The formed glue establishes an adhesive and robust barrier to seal the arterial, hepatic, and cardiac hemorrhagic wounds, enabling it to withstand up to 380 mmHg blood pressure in comparison with normal systolic blood pressure of 60-180 mmHg. Remarkably, massive bleeding from a pig cardiac penetrating hole with 6 mm diameter is effectively stopped using the glue within 60 s. Postoperative indexes of the treated pig gradually recover and the cardiac wounds regrow significantly at 14 days. Possessing on-demand solubility, self-gelling, and rapid degradability, the AG-PEG glue may provide a fascinating stop-bleeding approach for clinical hemostasis and emergency rescue.

Hydrogel-Based Biomaterials Engineered from Natural-Derived Polysaccharides and Proteins for Hemostasis and Wound Healing.

Rapid and effective hemostasis is of great importance to improve the quality of treatment and save lives in emergency, surgical practice, civilian, and military settings. Traditional hemostatic materials such as tourniquets, gauze, bandages, and sponges have shown limited efficacy in the management of uncontrollable bleeding, resulting in widespread interest in the development of novel hemostatic materials and techniques. Benefiting from biocompatibility, degradability, injectability, tunable mechanical properties, and potential abilities to promote coagulation, wound healing, and anti-infection, hydrogel-based biomaterials, especially those on the basis of natural polysaccharides and proteins, have been increasingly explored in preclinical studies over the past few years. Despite the exciting research progress and initial commercial development of several hemostatic hydrogels, there is still a significant distance from the desired hemostatic effect applicable to clinical treatment. In this review, after elucidating the process of biological hemostasis, the latest progress of hydrogel biomaterials engineered from natural polysaccharides and proteins for hemostasis is discussed on the basis of comprehensive literature review. We have focused on the preparation strategies, physicochemical properties, hemostatic and wound-healing abilities of these novel biomaterials, and highlighted the challenges that needed to be addressed to achieve the transformation of laboratory research into clinical practice, and finally presented future research directions in this area.

Graphene and its Derivatives for Bone Tissue Engineering: In Vitro and In Vivo Evaluation of Graphene-Based Scaffolds, Membranes and Coatings.

Bone regeneration or replacement has been proved to be one of the most effective methods available for the treatment of bone defects caused by different musculoskeletal disorders. However, the great contradiction between the large demand for clinical therapies and the insufficiency and deficiency of natural bone grafts has led to an urgent need for the development of synthetic bone graft substitutes. Bone tissue engineering has shown great potential in the construction of desired bone grafts, despite the many challenges that remain to be faced before safe and reliable clinical applications can be achieved. Graphene, with outstanding physical, chemical and biological properties, is considered a highly promising material for ideal bone regeneration and has attracted broad attention. In this review, we provide an introduction to the properties of graphene and its derivatives. In addition, based on the analysis of bone regeneration processes, interesting findings of graphene-based materials in bone regenerative medicine are analyzed, with special emphasis on their applications as scaffolds, membranes, and coatings in bone tissue engineering. Finally, the advantages, challenges, and future prospects of their application in bone regenerative medicine are discussed.

Second sacral sacralalar-iliac (S2AI) screw placement in adult degenerative scoliosis (ADS) patients: an imaging study.

BACKGROUND: The imaging characteristics of sacral sacralalar-iliac (S2AI) screw trajectory in adult degenerative scoliosis (ADS) patients will be determined. METHODS: S2AI screw trajectories were mapped on three-dimensional computed tomography (3DCT) reconstructions of 40 ADS patients. The starting point, placement plane, screw template, and a circle centered at the lowest point of the ilium inner cortex were set on these images. A tangent line from the starting point to the outer diameter of the circle was selected as the axis of the screw trajectory. The related parameters in different populations were analyzed and compared. RESULTS: The trajectory length of S2AI screws in ADS patients was 12.00 ± 0.99 cm, the lateral angle was 41.24 ± 3.92°, the caudal angle was 27.73 ± 6.45°, the distance from the axis of the screw trajectory to the iliosciatic notch was 1.05 ± 0.81 cm, the distance from the axis of the screw trajectory to the upper edge of the acetabulum was 1.85 ± 0.33 cm, and the iliac width was 2.12 ± 1.65 cm. Compared with females, the lateral angle of male ADS patients was decreased, but the trajectory length was increased (P < 0.05). Compared to patients without ADS in previous studies, the lateral angle of male patients was larger, the lateral angle of female patients was increased, and the caudal angle was decreased (P < 0.05). CONCLUSIONS: There is an ideal trajectory of S2AI screws in ADS patients. A different direction should be noticed in the placement of S2AI screws, especially in female patients.

A novel integrated global coronal aligner helps prevent post-operative standing coronal imbalance in adult spinal deformity patients fused to pelvis: technical notes and preliminary results.

BACKGROUND: Chieving postoperative coronal balance in adult spinal deformity correction surgeries can be challenging. Even with T square rod technique, there were still some cases with good intraoperative coronal alignment but unsatisfactory post-operative standing coronal imbalance. Thus, the novel techniques to obtain global coronal balance are still in great needs. The purpose of this study was to describe a novel integrated global coronal aligner (IGCA) and evaluate its efficacy on avoidance of post-operative coronal imbalance in adult spinal deformity patients fused to pelvis. METHODS: A detailed description of IGCA technique was presented. 52 ASD patients fused to pelvis were divided into two groups (IGCA group, n = 27; and non-IGCA group, n = 25) according to whether intraoperative IGCA was used or not. Preoperative demographics and postoperative outcomes were compared. RESULTS: There were no significant differences regarding coronal balance difference (CBD) and imbalance/balance ratio between IGCA and non-IGCA groups preoperatively. After surgery, CBD in IGCA group was significantly improved from 24.7 ± 20.3 mm preoperatively to 12.6 ± 6.4 mm postoperatively (t = 3.185 p = 0.004), and imbalance/balance ratio decreased significantly from 55.6% (15/27) preoperatively to 11.1% (3/27) postoperatively (χ2 = 12.000, p = 0.001), while CBD and imbalance/balance ratio in non-IGCA group were not significantly improved. Compared to non-IGCA group, the amount of correction in CBD was significantly larger in IGCA group (t = 3.274, P = 0.002), and imbalance/balance ratio in IGCA group was significantly lowered (χ2 = 8.606 p = 0.003). Further logistic regression analysis revealed IGCA technique was associated with increased odds ratio for postoperative coronal balance (odds ratio: 7.385; 95% confidence interval 1.760-30.980; P = 0.006). CONCLUSIONS: The novel intraoperative IGCA technique could help improve CBD and reduce imbalance/balance ratio. It could help prevent post-operative coronal imbalance in adult spinal deformity patients fused to pelvis. LEVEL OF EVIDENCE: 3.

In vivo evaluation of bending strengths and degradation rates of different magnesium pin designs for oral stapler.

Magnesium alloys have been potential biodegradable implants in the areas of bone, cardiovascular system, gastrointestinal tract, and so on. The purpose of this study is to evaluate Mg-2Zn alloy degradation as a potential suture material. The study included Sprague-Dawley (SD) rats in vivo. In 24 male SD rats, tests in the leg muscle were conducted using traditional surgical incision and insertion of magnesium alloys of different designs into the tissue. The material degradation topography, elemental composition, and strength of the pins were analyzed. This paper explores magnesium pins with different cross-sectional shapes and diameters to establish a suitable pin diameter and shape for use as an oral stapler, which must have a good balance of degradation rate and strength. The results showed there were good bending strengths over different degradation periods in groups with diameters of 0.8 mm and 0.5 mm, and no significantly different bending strength between the groups of triangle and round cross-section shapes with same diameter of 0.3 mm, although the degradation rate still needs to be improved.

Spontaneous Remodeling of Spinal Canal After Sagittal Translation in Pedicle Subtraction Osteotomy for Correction of Thoracolumbar Kyphosis in Ankylosing Spondylitis.

BACKGROUND: Sagittal translations (STs) secondary to osteotomy for the correction of ankylosing spondylitis (AS) kyphosis have drawn great attention, which is considered closely related to neurologic deficits and terrible fusion. Despite being discussed in several cases, there were no relevant reports about the transformation of ST and the spinal canal remodeling in AS patients. METHODS: Retrospective analysis was conducted on 16 patients with ST for the treatment of AS kyphosis through pedicle subtraction osteotomy during January 2011 to December 2014 in our hospital. Full-length free-standing spinal radiographs were available for all patients before and after surgery and also at the final follow-up. Radiologic parameters including global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA), and ST were measured. Rates of ST transformation after the surgery and at 1-year follow-up were compared. RESULTS: The average follow-up was 22 months, ranging from 12-36 months. There was no internal fixation failure during this period. The preoperative GK was 59.9 ± 21.0°, TLK was 38.0 ± 13.0°, LL was 7.4 ± 26.5°, and SVA was 27.2 ± 8.6 mm. The postoperative GK was 15.7 ± 2.1°, TLK was 5.6 ± 2.6°, LL was -36.1 ± 2.9°, and SVA was 6.1 ± 4.3 mm. ST was 7.1 ± 2.7 mm after surgery and 1.2 ± 1.0 mm at 1-year follow-up. The difference was statistically significant (P < 0.05). The rate of ST transformation was 84.9% ± 9.7%. According to Scoliosis Research Society surveys, the preoperative and the final follow-up satisfaction score was 1.6 ± 0.3 and 4.7 ± 0.4 respectively (P < 0.05). Remodeling of the spinal canal happened to all the patients with different degrees. CONCLUSIONS: All patients with ST after pedicle subtraction osteotomy for AS kyphosis occurred with spontaneous remodeling of the spinal canal at 1-year follow-up, by which ST can decrease in different degrees or even disappear, and favorable fusion can be achieved even without bone grafting into the osteotomy vertebra.

Optimal Pelvic Incidence Minus Lumbar Lordosis Mismatch after Long Posterior Instrumentation and Fusion for Adult Degenerative Scoliosis.

OBJECTIVE: To evaluate the influence of Scoliosis Research Society (SRS)-Schwab sagittal modifiers of pelvic incidence minus lumbar lordosis mismatch (PI-LL) on clinical outcomes for adult degenerative scoliosis (ADS) after long posterior instrumentation and fusion. METHODS: This was a single-institute, retrospective study. From 2012 to 2014, 44 patients with ADS who underwent posterior instrumentation and fusion treatment were reviewed. Radiological evaluations were investigated by standing whole spine (posteroanterior and lateral views) X-ray and all radiological measurements, including Cobb's angle, LL, PI, and the grading of vertebral rotation, were performed by two experienced surgeons who were blind to the operations. The patients were divided into three groups based on postoperative PI-LL and the classification of the SRS-Schwab: 0 grade PI-LL (<10°, n = 13); + grade PI-LL (10°-20°, n = 19); and ++ grade PI-LL (>20°, n = 12). The clinical outcomes were assessed according to Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), Visual Analog Scale (VAS), Lumbar Stiffness Disability Index (LSDI), and complications. Other characteristic data of patients were also collected, including intraoperative blood loss, operative time, length of hospital stay, complications, number of fusion levels, and number of decompressions. RESULTS: The mean operative time, blood loss, and hospital stay were 284.5 ± 30.2 min, 1040.5 ± 1207.6 mL, and 14.5 ± 1.9 day. At the last follow-up (2.6 ± 0.6 years), the radiological and functional parameters, except the grading of vertebral rotation, were all significantly improved in comparison with preoperative results (P < 0.05), but it was obvious that an ideal PI-LL (≤10°) was not achieved in some patients. Significant differences were only observed among the three groups in the ODI and LSDI. Patients with + grade PI-LL seemed to have the best surgical outcome compared to those with 0 and ++ grade PI-LL, with the lowest ODI score (+ grade vs 0 grade, 17.3 ± 4.9 vs 26.0 ± 5.4; + grade vs ++ grade, 17.3 ± 4.9 vs 32.4 ± 7.3; P < 0.05) and lower LSDI (+ grade vs 0 grade, 1.6 ± 1.0 vs 3.5 ± 0.5, P < 0.05; + grade vs ++ grade, 1.6 ± 1.0 vs 0.6 ± 0.5, P > 0.05). A Pearson correlation analysis further demonstrated that LSDI was negatively associated with PI-LL. Furthermore, the incidence rate of postoperative complications was lower in patients with + grade PI-LL (1/19, 5.26%) than that in patients with 0 (2/13, 15.4%) and ++ grade PI-LL (3/12, 25%). CONCLUSION: Our present study suggest that the ideal PI-LL may be between 10° and 20° in ADS patients after long posterior instrumentation and fusion.

Hepatic stellate cells in inflammation-fibrosis-carcinoma axis.

Almost 80% of hepatocellular carcinoma (HCC) cases are associated with chronic hepatitis and cirrhosis resulting from inflammation and fibrosis. A three-step process of "inflammation-fibrosis-carcinoma" is believed to be involved in hepatocarcinogenesis. The activation of hepatic stellate cells (HSCs) may serve as an important mediator in the process of inflammation-fibrosis-carcinoma axis, even in tumor metastasis. A remarkable knowledge of activated HSCs in the pathology of HCC development is mostly focused on the liver fibrosis. The molecular links that connects inflammation and cancer in the activation of HSC are not completely known. This highlights urgent need to increase our understanding of the cellular and molecular mechanisms, by which activation of HSCs is involved in the hepatic inflammation, carcinogenesis, and metastasis.