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During the Rituximab era, high dose intravenous methotrexate (HD) and intrathecal methotrexate (IT) are recommended prophylaxis in preventing central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) patients. However, the optimal CNS prophylaxis strategies remained uncertain. This meta-analysis research explored the findings of previous studies and highlighted the efficacy of HD and/or IT on CNS prophylaxis of DLBCL patients at intermediate to high risk. Specifically, it aims to answer the following research questions: (1) Is there a difference on CNS relapse rate between HD and IT cohorts? (2) Is there a correlation between CNS prophylaxis and survival? This meta-analysis research performed an in-depth examination of pertinent studies available in PubMed, Embase, and Cochrane databases. The primary endpoints included: CNS relapse rate and 2-year or 3-year survival rate. The findings of the qualified studies were reviewed and analyzed using 5.3 version of the Review Manager software. After thorough analysis of 12 studies involving 5950 DLBCL patients, it was revealed that in comparison with IT alone, HD with or without additional IT (HD ± IT) significantly reduced the risk of CNS relapse (Risk Ratio (RR)= 0.41, 95 % CI (0.24-0.68), P = 0.0007). Besides, the efficacy of HD alone was comparable to HD + IT (RR = 1.08, 95 % CI (0.19-6.32), P = 0.93), which was also considered to be more optimal than IT alone on CNS prophylaxis (RR = 0.39, 95 % CI (0.15-1.06), P = 0.06).Based on these results, IT alone or no-prophylaxis were viewed as a group of inadequate prophylaxis. Comparing to HD ± IT, the 3-year survival rate of inadequate prophylaxis group was lower (RR = 1.17, 95 % CI (1.03-1.32), P = 0.01). The results of this study reveals that in the Rituximab Era, prophylaxis strategies containing HD is better than IT alone or no-prophylaxis on preventing CNS relapse of DLBCL patients with intermediate to high risk.

The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors.

Background To compare the diseased verses the non-diseased intervertebral surgery used in the treatment of thoracolumbar and lumbar spinal tuberculosis and to explore the best choice of fusion of fixation range. Methods Two hundred twenty-one patients with thoracolumbar and lumbar tuberculosis were categorized into two groups. One hundred eighteen patients underwent the diseased intervertebral surgery (lesion vertebral pedicle fixation, Group A) and 103 patients underwent the non-diseased intervertebral surgery (1 or 2 vertebral fixation above and below the affected vertebra, group B). Spinal tuberculosis diagnosis was confirmed in both groups of patients before lesion removal, bone graft fusion, and internal fixation. Clinical data and efficacy of the two surgical methods were then evaluated. Results The mean follow-up duration for both procedures was 65 months (50–68 months range). There were no significant differences in laboratory examinations, VAS scores, and the Cobb angle correction rate and the angle loss. However, significant differences existed in the operation time, blood loss, serosanguineous drainage volume, and blood transfusion requirement between the two groups. The diseased intervertebral surgery group performed significantly better than the non-diseased intervertebral surgery group in all of these areas. In both cases, the bone graft fused completely with the normal bone by the last follow-up, occuring at 50–86 months post surgery. Conclusion The diseased intervertebral surgery is a safe and feasible option for the treatment of thoracolumbar and lumbar tuberculosis. It effectively restores the physiological curvature of the spine and reduces the degeneration of adjacent vertebral bodies in the spinal column.

Background Infrapatellar fat pad (IPFP) is regarded as an essential knee tissue involved in osteoarthritis (OA) for its potential structural-related or metabolism-related function. This cross-sectional study aims to identify which part is more related to OA. Methods Patients with knee OA ( n = 53) and healthy controls ( n = 54) were prospectively recruited. Based on high-resolution magnetic resonance imaging with a slice thickness of only 0.35 mm, IPFP structural-related parameters (volume and maximal area), metabolism-related parameter (signal), degeneration indicators, and patellar maltracking indicators (patellar translation, patellofemoral angle, and Insall-Salvati ratio) were measured. IPFP volume (maximal area, and signal) was compared between healthy controls and OA patients. The level of significance for all comparisons was set as .05. Results OA patients had higher IPFP signal (672.9 ± 136.9 vs 567.3 ± 63.6, p = .009), but no significant difference in IPFP volume or maximal area compared with healthy controls. In healthy controls, IPFP signal was positively associated with age ( β = 1.481; 95% CI: 0.286–2.676; p = .018); IPFP maximal area was positively related to Insall-Salvati ratio ( β = 0.001; 95% CI: 0.0003–0.0017; p = .039), but not associated with patellar translation and patellofemoral angle. In OA patients, IPFP signal was positively associated with cartilage loss ( β = 0.005; 95% CI: 0.003–0.007; p = .013); no correlation between knee pain and IPFP volume or maximal area was observed. Conclusions The metabolism-related function of IPFP, which can be reflected by the IPFP signal, might play a more critical role in OA progression than its structural function.

Purpose Liquid biopsy refers to the detection and analysis of the components from biological fluids non-invasively, including circulating tumor cells, nucleic acids, and extracellular vesicles (EVs). It is necessary to review the clinical value of liquid biopsy assays in PC and explore its potential application. Materials and methods We systematically reviewed of PubMed was performed to identify relevant literature on potential clinical applications of circulating tumor cells, circulating nucleic acids, and EVs in prostate cancer (PC). Results Liquid biopsy has emerged as a powerful tool to elucidate dynamic genomic, transcriptomic, and epigenomic tumor profiling in real-time. Here, the potential clinical applications of liquid biopsy include early detection, prognosis of survival, assessment of treatment response, and mechanisms of drug resistance in PC. Conclusions Liquid biopsy provides great value in diagnosis, prognosis, and treatment response in PC. Characterization of liquid biopsy components provides benefits both to unravel underlying resistance mechanisms and to exploit novel clinically actionable targets in PC. In addition, we suggest that analysis of multiparametric liquid biopsies should be analyzed comprehensively, assisting in monitoring tumor characteristics in real-time, guiding therapeutic selection, and early therapeutic switching during disease progression.

BACKGROUND The L1-2 vertebral segment is the most common site of spinal tuberculosis. Traditional thoracoabdominal surgery in this segment risks trauma and complications. This study analyzed the surgical efficacy of the subdiaphragmatic extraperitoneal approach in the treatment of L1-2 spinal tuberculosis. MATERIAL AND METHODS Retrospective analysis of 67 patients with L1-2 vertebral tuberculosis who underwent posterior internal fixation was performed: 35 patients underwent the subdiaphragmatic extraperitoneal approach (group A) and 32 underwent the thoracoabdominal approach (group B). Operation time, intraoperative blood loss, postoperative hospital stay, postoperative nerve function recovery, deformity correction, bone graft fusion, lesion healing, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complications were observed. RESULTS In group A and group B, intraoperative blood loss was 712.00±64.66 mL and 1104.38±131.34 mL; average operation time was 3.16±0.67 h and 5.16±1.07 h; and postoperative hospital stay was 9.60±2.64 days and 13.69±3.87 days, respectively. At 6 months and 5 years after surgery, neurological function, visual analog scale score, and Cobb angle of all patients were significantly improved compared with those before surgery; ESR and CRP decreased to normal levels; lesions completely cured; and all patients had good bone graft fusion. Pulmonary complications occurred in 2 patients in group A and in 14 patients in group B. CONCLUSIONS The efficacy of subdiaphragmatic extraperitoneal approach was similar to that of the thoracoabdominal approach for L1-2 spinal tuberculosis, but the former has the advantages of less surgical trauma, shorter operation time, less intraoperative bleeding, and fewer postoperative pulmonary complications.

To observe anatomic relationships between lumbar bicortical pedicle screws (BPSs) at 2 sagittal section angles (SSAs) and lumbar artery (LA).We observed 2 SSAs, vertical angle and cephalic angle, of the BPS. The positions at which the BPS breaks through the anterior vertebral cortex were defined as point A and point B. Distances from point A and point B to LAs were measured. The percentage of risk of injury to LAs was calculated according to these distances.At the same transverse section angle on the left and right side in L1 and L2, distance from point A to LA was significantly greater than distance from point B to LA (P0.001) except at a transverse section angle of 0° on the right side in L2 (P0.05). At the same transverse section angle on the left in L3 and L4, distance from point B to LA was significantly greater than distance from point A to LA (P0.001). The percentages of high risk of injury to the LA resulting from BPSs at the vertical angle in L1 and L2 were 0%-6.2%. The percentages of high risk of injury to the LA resulting from BPSs at the cephalic angle on the left side in L3 and L4 were 0%-18.5%.Lumbar BPSs present a risk of injury to the LA. The vertical angle is the recommended SSA for BPSs in L1 and L2, and the cephalic angle is the recommended SSA in L3 and L4.

The present retrospective comparative analysis was conducted to assess the effectiveness of affected-vertebrae fixation versus short-segment fixation to treat thoracic spinal tuberculosis.The present study included 110 patients receiving treatment for thoracic spinal tuberculosis at our hospital from January 2006 to June 2013. All cases involved the use of posterior spinal correction, posterior lateral fusion, internal fixation, anterior decompression, radical debridement, and intervertebral supporting bone grafts. The cases were divided by the scope of posterior internal fixation into the affected-vertebrae fixation group (n = 62) and the short-segment fixation group (n = 48). Statistical analysis was used to compare the clinical effectiveness, laboratory test results, and imaging findings.The mean surgical blood loss, mean operating time, and mean inpatient expenditures were all significantly less in the affected-vertebrae fixation group than in the short-segment fixation group (P0.05). The affected-vertebrae fixation group had a lower mean graft fusion time (5.21 vs. 5.06 months), mean healing time (5.73 vs. 5.91 months), mean degree of correction of thoracic vertebrae kyphosis Cobb angle (16.9° vs. 18.4°), and mean loss of angle (2.6° vs. 2.1°) compared with the short-segment fixation group. However, these differences all lacked statistical significance. Postoperatively, neurological deficits and pain were effectively relieved in all patients, and the lesion had healed at the final follow-up evaluation (≥5 years postoperatively).As long as the surgical indications are strictly observed, posterior affected-vertebrae fixation in posterior-anterior surgery for thoracic spinal tuberculosis is safe, effective, and feasible; entails minimal surgical trauma; and has a lower inpatient cost.

Herein, N-(4-aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal-organic frameworks (ABEI/MIL-101(Fe)) with intrinsic mimic peroxidase activity was synthesized and utilized as highly efficient ECL indicator to construct sensitive immunosensor for mucin1 (MUC1) detection. Firstly, compared with the traditional method for ABEI immobilization, the proposed strategy could successfully achieve the highly efficient ABEI immobilization as ABEI coupled 2-aminoterephhalic acid was used as organic bridge ligand. Moreover, the ABEI/MIL-101(Fe) containing the same luminescent group as luminol could emit strong light when using hydrogen peroxide (H2O2) as a co-reactant. It is worth noting that the ECL signal of ABEI/MIL-101(Fe) could be greatly heightened due to the intrinsic mimic peroxidase activity of ABEI/MIL-101(Fe) that could accelerate the decomposition of H2O2 and produce considerable numbers of reactive oxygen radicals to participate in the ECL reaction of ABEI. The fabricated ECL immunosensor displayed a low detection limit of 1.6 fg mL−1 for MUC1, indicating that the synthesized ABEI/MIL-101(Fe) with intrinsic mimic peroxidase activity may be applied to realize ultrasensitive detection of other biomarkers in early diagnosis.

Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.

Background Percutaneous vertebroplasty (PVP) has been widely used to treat vertebral pathological fractures in recent decades, and the modified PVP instrument is very suitable for percutaneous biopsy of diseases promoting vertebral bone destruction. The purpose of this study was to evaluate the relevance of the clinical application of the modified PVP instrument in computed tomography-guided (CT-guided) biopsies of the vertebral body. Methods Retrospective analysis of clinical data obtained by percutaneous biopsy using a modified PVP outer shell of a bone filler device (OSBF) from 161 patients presenting vertebral body destruction was conducted. The rate of correctly performed biopsy diagnosis was evaluated from three aspects: imaging performance, histological type, and vertebral segment. Results The results of 149 biopsy cases were consistent with the final clinical diagnosis. From those cases, 92 were diagnosed as vertebral body metastasis, 45 cases presented primary spinal tumors and tumor-like changes, 7 cases presented vertebral body infections, and 5 cases displayed normal bones or fractures. From the remaining 12 patients, whose biopsy results were inconsistent with the final clinical diagnosis, 4 presented vertebral metastases, 4 displayed primary vertebral tumors, and 4 presented vertebral infections. The diagnostic rate of the modified PVP OSBF biopsy was 92.5%. The rate of correct biopsy diagnosis for vertebral metastases was 95.8%. The rate of correct diagnosis of primary vertebral tumors and tumor-like biopsy was 91.8%, and the rate of correct diagnosis for vertebral infectious diseases was 63.6%. Conclusion The modified PVP OSBF allows obtaining more lesion tissue, in multiple directions and multiple angles, during the biopsy of vertebral bones presenting destructive lesions. The technique displays appropriate safety and high diagnostic accuracy and presents a desirable reference value for the preoperative diagnosis of diseases that yield vertebral bone destruction, especially for vertebral tumor lesions.

Adhesive hydrogels have been developed for wound healing applications. However, their adhesive performance is impaired dramatically due to their high swelling on wet tissues. To tackle this challenge, we fabricated a new type of non‐swelling protein adhesive for underwater and in vivo applications. In this soft material, the electrostatic complexation between supercharged polypeptides with oppositely charged surfactants containing 3,4‐dihydroxylphenylalanine or azobenzene moieties plays an important role for the formation of ultra‐strong adhesive coacervates. Remarkably, the adhesion capability is superior to commercial cyanoacrylate when tested in ambient conditions. Moreover, the adhesion is stronger than other reported protein‐based adhesives in underwater environment. The ex vivo and in vivo experiments demonstrate the persistent adhesive performance and outstanding behaviors for wound sealing and healing., Non‐swelling protein‐based coacervate adhesives for in vivo applications were fabricated by employing electrostatic complexation of supercharged polypeptides (SUPs) and oppositely charged surfactants. The adhesives exhibited superior performance compared to other reported protein‐based adhesives. The outstanding adhesion performance, good biocompatibility, and biodegradability of SUP adhesives facilitate fast wound healing and skin regeneration.

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures., Biomedical glues often face a challenge in providing strong adhesion and providing remodelling capabilities. Here the authors report on the development of a biocompatible and biodegradable protein-based coacervate adhesive and demonstrate application in haemostasis and wound healing using pig models.

Recently, the accumulation of senescent cells (SnCs) within joints was found to promote osteoarthritis (OA) progression. Our previous study found that Wnt proteins, especially Wnt10a, have marked effects on cellular senescence and joint health. However, the effect of WNT10A on SnCs in OA joints remains unknown. In this study, we confirmed that the synovium was the first and most marked site of SnC accumulation in the OA joint, and synovial resident mesenchymal stem cells (SMSCs) seemed to be the main source of these SnCs. In synovium samples from OA patients, WNT10A level inversely correlated with the extent of SnCs accumulation. Therefore, we further explored the possible regulatory role and mechanism of WNT10A in intraarticular senescent SMSCs. In brief, we confirmed that WNT10A could specifically clear these senescent OA-SMSCs in vitro experiments and naturally occurring OA models via proapoptotic effects. Mechanistically, WNT10A activated noncanonical Wnt/calcium signaling in senescent OA-SMSCs, which in turn induced histone deacetylase 5 (HDAC5) phosphorylation and nuclear export via its downstream Ca2+/calmodulin-dependent protein kinase II (CaMKII) to regulate cell fate. The regulation of this pathway significantly improved the regenerative microenvironment of OA, exhibiting its potential as a novel clinical disease-modifying OA drugs (DMOADs) target.

Purpose We investigate the orientation tuning of interocular suppression using a dichoptic masking paradigm in adult controls and amblyopes. Methods Fourteen adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. Contrast sensitivity was measured by presenting a target Gabor in the tested eye and mean luminance in the untested eye (monocular) and by presenting a target in the tested eye and a bandpass oriented filtered noise in the other eye (masked). Interocular suppression was defined as the thresholds difference between the monocular and masked conditions for each eye. Interocular suppression was measured under parallel and orthogonal suppression configurations. The peak spatial frequency of the target and mask was 0.25 c/d in experiment 1 (low), 1.31 c/d in experiment 2 (mid), and 6.87 c/d in experiment 3 (high). Results The masking suppression induced by the amblyopic eye was less strong than that induced by the fellow eye. The suppression from the fellow eye was similar to that observed in the controls. Interocular suppression under parallel configuration was less strong than under orthogonal configuration in amblyopes at low and mid spatial frequency, but not at high spatial frequency. Conclusions We demonstrate that the abnormal interocular masking in amblyopia displays the expected characteristic of orientation selectivity expected of normal controls at low and mid spatial frequency, but not at high spatial frequency. The dichoptic masking imbalance between the eyes of amblyopes results in a net suppression of the amblyopic eye during binocular viewing, modeling clinical suppression.

Melanoma is the most lethal malignancy in skin cancer and may occur at any site and express melanocytes. Due to malignant melanoma's invasion and migration nature, conventional therapies make it challenging to remove the whole tumor tissue while undertaking the high risks of tumor recurrence. Regarding the emerging targeted therapies and immunotherapy, drug resistance and low immunotherapeutic activity remain significant challenges. It is thus becoming urgently important to develop alternative strategies for melanoma therapy. Herein, a novel bifunctional protein-based photothermal bioplaster (PPTB) is developed for non-invasive tumor therapy and skin tissue regeneration. The complexation of adhesive protein and gold nanorods (GNRs) endow the obtained PPTB with good biocompatibility, controllable near-infrared (NIR) light-mediated adhesion performance, and high photothermal performance. Therefore, the PPTB bioagent facilitates skin adhesion and effectively transfers heat from skin to tumor. This behavior endows PPTB capability to eradicate skin tumors conveniently. Thus, the assembly strategy enables this hybrid bioplaster to hold great potential for skin-related tumor treatment.

In this study, we used LS174T cells as a model to investigate the protective effects of icariin and phosphorylated icariin on LPS-induced goblet cell dysfunction. Our results indicated that icariin and phosphorylated icariin increased the cell viability and decreased lactate dehydrogenase activity in LPS-treated LS174T cells. Icariin and phosphorylated icariin attenuated LPS-induced changes in mucin 2 synthesis and secretion. Besides, Icariin and phosphorylated icariin reduced the levels of ROS, MDA, and H2O2 and increased the activity of SOD, GPx, CAT, and T-AOC in LPS-treated LS174T cells. Moreover, the levels of IL-1β, IL-6, IL-8, and TNF-α were reduced in the Icariin and phosphorylated icariin group. Furthermore, Icariin and phosphorylated icariin decreased gene abundance or enzyme activity of Bip, XBP1, GRP78, CHOP, caspase-3, and caspase-4 in LPS-treated LS174T cells. Our data suggest that Icariin and phosphorylated icariin effectively attenuate LPS-induced intestinal goblet cell function damage through regulating oxidative stress, inflammation, apoptosis, and mucin expression.

Objective For non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutations are predictive markers of the treatment benefit from selective tyrosine kinase inhibitors (TKI). However, their prognostic roles remained uncertain. Thus, we conducted this meta-analysis to evaluate the prognosis of ALK+ NSCLC patients in the treatment of surgery, chemotherapy, and/or EGFR-TKI. Materials and methods PubMed, Embase and Cochrane databases were thoroughly searched to identify relevant studies. Primary endpoints of this study included overall survival (OS), recurrence/progression free survival (RFS/PFS) and objective response rate (ORR). All statistical analyses were performed via REVIEW MANAGER (version 5.3). Results In total, 15 studies involving 4981 NSCLC patients were included. This study demonstrated that smoking status profoundly influenced prognosis of ALK related NSCLC. In the general population with NSCLC, compared with ALK- arm, ALK+ arm obtained a significantly better prognosis (HR = 0.81 for OS, 95% CI = 0.72-0.91; 0.80 for RFS/PFS, 95% CI = 0.70-0.90), even after further stratification analysis according to disease stage. However, in the non-smoking population with NSCLC, compared with ALK- arm, those in the ALK+ arm had a worse prognosis (HR = 1.65 for OS, 95% CI = 1.28-2.12; 1.23 for RFS/PFS, 95% CI = 1.05-1.44). Furthermore, ALK+ patients experienced a significantly higher ORR in pemetrexed-based chemotherapy but not in EGFR-TKI. Conclusions Smoking status had a profound influence on the ALK-related prognosis of NSCLC. ALK rearrangement predicted a better prognosis in the general population with NSCLC, but a poor survival in the non-smoking population. Therefore, stratification according to smoking status is strongly recommended for future studies exploring ALK-related prognosis.

Herein, a high-efficiency electrochemiluminescence (ECL) indicator of an abundant N-(aminobutyl)-N-(ethylisoluminol) functionalized metal-organic framework (ABEI@Fe-MIL-101) was synthesized to construct a biosensor for the ultrasensitive assay of mucin1 on MCF-7 cancer cells with a coreactant H2O2-free strategy.

Background At present, bicortical pedicle screws (BPSs) are not used clinically because they carry the potential risk of damaging the prevertebral great vessels (PGVs). The authors observed the anatomical relationship between the PGVs and simulated BPSs at different transverse screw angles (TSAs), exploring the insertion method of the BPS. Methods Computed tomography angiography (CTA) images from 65 adults were collected. A total of 4–5 TSAs of the BPSs were simulated on the left and right sides of L1-L5 (L1-L3: 0°, 5°, 10°, 15°; L4-L5: 0°, 5°, 10°, 15°, 20°). There were three types of distances from the anterior vertebral cortex (AVC) to the PGVs (DAVC-PGV); DAVC-PGV

During the operation of treating lumbar tuberculosis in children, a long-segment or short-segment fixation, and fusion method were usually applied, which would adversely affect the function of normal motion unit. And so, we have been focusing on how we can shorten the range of fixation and fusion using intervertebral surgery. The objective of this retrospective study is to investigate the clinical outcome of intervertebral surgery, in the treatment of lumbar tuberculosis in children. From June 2003 to June 2013, 18 children with lumbar tuberculosis underwent intervertebral surgery, using a combined posterior and anterior approach, in our hospital. The surgical treatments included posterior pedicle screw fixation of affected vertebrae and posterolateral bone grafting, anterior debridement, compression, and strut bone grafting. Indicators such as preoperative and postoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, neurological function, visual analog scale (VAS) score, kyphotic Cobb angle, complications, healing of lesions, bone graft healing, and recurrence were statistically analyzed. The mean follow-up time was 86.5 months (range, 62–120 months). Three months after the operation, all patients’ ESR and CRP levels decreased to normal, and both the American Spinal Injury Association neurological function scores and VAS scores improved. Successful bone graft healing was achieved, with lesions completely healed at 6 months after surgery, and no recurrence occurred. The preoperative kyphotic was 24.00° ± 13.15° (range −10°–39°), which decreased to −4.61° ± 7.31° (range −19°–10°) postoperative (Z = −4.34, P

SUMMARY OBJECTIVE: To investigate the efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of lumbar spinal stenosis (LSS) combined with osteoporosis. METHODS: Eighty patients with LSS combined with osteoporosis were divided into a control and PTED group, which received conventional transforaminal lumbar interbody fusion and PTED, respectively. The surgical indications, incision visual analogue scale (VAS), lumbar and leg pain VAS, lumbar Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) scores, bone mineral density (BMD), and adverse reactions were observed. RESULTS: Compared with the control group, in the PTED group, the operation time, bleeding loss and hospitalization duration, incision VAS scores at postoperative 12, 24 and 48 h and lumbar and leg pain VAS and lumbar ODI scores on postoperative 6 months were significantly decreased (P < 0.01), and the lumbar JOA score on postoperative 6 months was significantly increased (P < 0.05). There was no significant difference in BMD between two groups (P > 0.05). Compared with the control group, in the PTED group, the total effective rate was significantly higher (P < 0.05), and the incidence of adverse reactions was significantly lower (P < 0.05). CONCLUSIONS: PTED is safe and effective in the treatment of LSS combined with osteoporosis.

CyclinB1 is a regulatory protein involved in mitosis. Multiple lines of evidence indicate that cyclinB1 depletion constrains proliferation and induces apoptosis in human tumor cells. The cells become susceptible to suffer a critical situation when cyclinB1 is downregulated. Autophagy is a major intracellular degradation system that recycles nutrients, removes damaged organelles, and promotes cell survival under stressful conditions, whereas the role of autophagy in cyclinB1-deprived neoplastic cell as well as the underlying molecular mechanism remains obscure. Here we pioneeringly elaborated that specific knockdown of cyclinB1 triggered autophagy via AMPK-ULK1-dependent signal pathway through the elevation of ROS, rather than ATP in the cell lines of CNE-1 and CNE-2. Moreover, ROS scavengers demonstrated that the observed effect of cyclinB1 silencing on AMPK phosphorylation was ROS dependent. Additionally, double knockdown of AMPK and cyclinB1 evidently abrogated cyclinB1 silencing-induced autophagy. Summarily, this study first revealed that downregulation of cyclinB1 induced autophagy via AMPK-ULK1-dependent signal pathway, which represents a key step toward unveiling the mechanism how cell cycle checkpoint proteins regulate autophagy.

Objective To evaluate the clinical efficacy and safety of ultra-short-course chemotherapy (Methods Clinical data of patients diagnosed with spinal tuberculosis, who underwent surgery with postoperative chemotherapy for Results Sixty patients were included, comprising 26 male and 34 female patients aged 16–78 years (mean, 40.85 years). Patients received postoperative chemotherapy for 3–4 months (mean, 3.61 months) and were followed for 25–129 months (mean, 70.61 months). Spinal tuberculosis recurred after surgery in one patient, who was cured by subsequent surgery. At the final follow-up, no symptoms of tuberculosis, local pain, abscess or sinus were observed. Daily life and working abilities were almost recovered in all patients. ESR and CRP levels were restored to normal, bone grafts fused, lesions healed and neurological functions were recovered. Postoperative chemotherapy-induced complications occurred in 10 patients (16.67%). Conclusions Complete debridement plus ultra-short-course chemotherapy for 3–4 months may be safe and efficacious in treating spinal tuberculosis, and requires further investigation.

An in vitro study using human intervertebral disc nucleus pulposus cells to evaluate the effects of CC stimulation on disc-matrix macromolecule production. Nucleus pulposus cells were cultured in alginate beads and treated with CC stimulation. The effect of BMP on CC stimulation of the cells was evaluated by applying a BMP blocker (noggin) or by applying additional BMP-7 to the culture. The mRNA levels of the disc extracellular matrix genes (collagen I, II, aggrecan) and BMPs were measured by real-time PCR. The protein levels of aggrecan, collagen II, and BMPs were determined by ELISAs and Western blots. Sulfated glycosaminoglycan (sGAG) content was assayed using the DMMB method. (1) CC stimulation upregulates the production of the disc-matrix macromolecular components: sGAG, aggrecan and collagen II; (2) CC stimulation increases the ratio of mRNA expression levels of collagen II to collagen I; (3) CC stimulation induces the expression of endogenous BMP-4 and BMP-7; (4) inhibition of BMP activity (using noggin) reduces CC-mediated upregulation of aggrecan and collagen II; (5) CC and BMP-7 act in synergy to increase the upregulation of disc-matrix macromolecules. CC stimulation upregulates the production of the intervertebral disc-matrix macromolecules aggrecan, collagen II, and sGAG by a mechanism involving BMPs. CC stimulation acts in synergy with BMP-7 to increase the upregulation of these disc-matrix macromolecules.

Background: Most degenerative lumbar spinal stenosis (DLSS) patients primitively received the conservative treatment to control symptoms. In order to develop an optimal surgical treatment strategy, it is very significant to understand how the degenerative lumbar spondylolisthesis (DS) affects the effect of decompression in the DLSS. Thus, the aim of this current study was to explore whether the concomitant DS would affect the effect of decompression alone in the patients with DLSS. Methods: The current study was carried out at our hospital and it was approved through our institutional review committee of General Hospital of Ningxia Medical University. During the period from January 2015 to December 2017, in our study, we identified consecutive patients who received the minimally invasive laminectomy to treat the DLSS. The inclusion criterion included radicular leg pain or neurogenic claudication with the neurological symptoms associated with DLSS syndrome, magnetic resonance imaging of the lumbar spine reveals at least 1 level of serious stenosis, the conservative treatment failed for at least 3 months, and patients agreed to provide the postoperative details. The major outcomes of this present research was Oswestry Disability Index. Secondary outcomes of this current study involved visual analog score, short form-36, surgical revision rate as well as complications. Results: We assumed that previous DS possessed a negative effect on the postoperative results of the DLSS patients. Trial registration: researchregistry5943.

Background We reviewed the reported data related to iatrogenic lumbar artery injury (ILAI) in spine surgery with a focus on which iatrogenic procedure might cause lumbar artery injury. Methods We conducted a comprehensive search in the Web of Science, PubMed, EMBASE, and Chinese biomedical databases in July 2018. Results A total of 20 reports on ILAI were selected for the present study. Most of these were case reports, with a total of 26 cases. The causes of ILAI were as follows: puncture injury in 9 cases, transforaminal endoscopic operation in 5 cases, pedicle screw injury in 3 cases, intervertebral foramen decompression in 2 cases, disc rongeur injury during discectomy in 2 cases, lumbar artery tear caused by transverse process fracture in 1 case, vertebral fracture restoration in 1 case, retractor injury in 1 case, cage insertion or pedicle screw injury in 1 case, and drainage tube stimulation in 1 case. The treatment methods included transarterial embolization in 20 cases, percutaneous embolization in 2 cases, surgical ligation in 1 case, and steroid and cyclophosphamide treatment in 1 case. All patients were treated successfully. One patient died during antishock therapy, and another patient died because her family refused any further intervention. Conclusions Attention should be given to the surgical procedures that are likely to cause ILAI, such as percutaneous vertebroplasty/percutaneous kyphoplasty, vertebral biopsy, pedicle screw implantation, discectomy, transforaminal endoscopic operation, and intervertebral foramen decompression. Once a diagnosis of ILAI has been confirmed, selective endovascular transarterial embolization is the preferred treatment.

BACKGROUND: In large rotator cuff tears, retraction of the supraspinatus muscle creates suprascapular nerve traction and compression. However, suprascapular nerve transection, when used in previous models, is different from chronic compression of the suprascapular nerve in patients. To define the role of suprascapular nerve chronic injury in rotator cuff muscle atrophy and fatty infiltration, we developed a novel reversible suprascapular nerve compression mouse model. QUESTIONS/PURPOSES: We asked: (1) Can suprascapular nerve injury be induced by compression but reversed after compression release? (2) Can muscle fatty infiltration be induced by suprascapular nerve compression and reversed after compression release? (3) Is white fat browning involved in fatty infiltration resorption? METHODS: Mice in a common strain of C57BL/6J were randomly assigned to suprascapular nerve transection (n = 10), nerve compression (n = 10), nerve compression and release (n = 10), or sham control (n = 10) groups. To study the role or white fat browning on muscle fatty infiltration, additional UCP1 reporter mice (n = 4 for nerve compression and n = 4 for nerve compression release) and knockout mice (n = 4 for nerve compression and n = 4 for nerve compression release) were used. Nerve injury was testified using osmium tetroxide staining and neural muscular junction staining and then semiquantified by counting the degenerating axons and disrupted junctions. Muscle fatty infiltration was evaluated using Oil Red O staining and then semiquantified by measuring the area fraction of fat. Immunofluorescent and Oil Red O staining on UCP1 transgenic mice was conducted to testify whether white fat browning was involved in fatty infiltration resorption. Ratios of UCP1 positively stained area and fat area to muscle cross-section area were measured to semiquantify UCP1 expression and fatty infiltration in muscle by blinded reviewers. Analysis of variance with Tukey post hoc comparisons was used for statistical analysis between groups. RESULTS: Suprascapular nerve injury was induced by compression but reversed after release. The ratios of degenerating axons were: sham control: 6% ± 3% (95% confidence interval [CI], 3%-10%); nerve compression: 58% ± 10% (95% CI, 45%-70% versus sham, p < 0.001); and nerve compression and release: 15% ± 9% (95% CI, 5%-26% versus sham, p = 0.050). The supraspinatus muscle percentage area of fatty infiltration increased after 6 weeks of nerve compression (19% ± 1%; 95% CI, 18%-20%; p < 0.001) but showed no difference after compression release for 6 weeks (5% ± 3%; 95% CI, 1%-10%; p = 0.054) compared with sham (2% ± 1%; 95% CI, 1%-3%). However, the fat area fraction in UCP1 knockout mice did not change after nerve compression release (6% ± 1%; 95% CI, 4%-8% at 2 weeks after compression and 5% ± 0.32%; 95% CI, 4%-6% after 2 weeks of release; p = 0.1095). CONCLUSIONS: We developed a clinically relevant, reversible suprascapular nerve compression mouse model. Fatty infiltration resorption after compression release was mediated through white fat browning. CLINICAL RELEVANCE: If the mechanism of browning of white fat in rotator cuff muscle fatty infiltration can be confirmed in humans, a UCP1 agonist may be an effective treatment for patients with suprascapular nerve injury.

To observe coronal imaging changes associated with recollapse of injured vertebrae after percutaneous vertebroplasty or percutaneous kyphoplasty for osteoporotic thoracolumbar fracture (OTLF).Fifty-four cases were retrospectively divided into 2 groups according to the Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF) classification of thoracolumbar fracture: group A, type A1 fracture (n = 26); group B, type A3.1 fracture (n = 28). Visual analog scale, Oswestry Disability Index, local scoliotic Cobb angle, and coronal wedge angle of the injured vertebrae were observed preoperatively, on postoperative day 3, and at final follow-up.The average follow-up time was 19.17 ± 6.30 months. At final follow-up, the visual analog scale score and the Oswestry Disability Index score were significantly greater in group B than in group A (both P0.05). At final follow-up, loss of correction of scoliotic Cobb angle and coronal wedge angle was significantly higher in group B than in group A (P0.05).Percutaneous vertebroplasty or percutaneous kyphoplasty was effective in both type A1 and type A3.1 OTLF. However, coronal imaging changes after percutaneous vertebroplasty or percutaneous kyphoplasty were more obvious in type A3.1 OTLF than in type A1. Moreover, clinical outcomes in type A3.1 OTLF were slightly inferior to those in type A1.

Background Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell–matrix interactions. Methods In this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically. Results In general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell–cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell–cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining. Conclusions The capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy. Electronic supplementary material The online version of this article (10.1186/s13287-018-0916-z) contains supplementary material, which is available to authorized users.

To determine the clinical efficacy of posterior intervertebral surgery for single-segment thoracolumbar spinal tuberculosis. Methods: Clinical data were retrospectively analyzed in 62 patients with thoracolumbar spinal tuberculosis who underwent posterior intervertebral surgery (A group) or posterior and anterior combined intervertebral surgery (B group) from January 2010 to January 2015 in Department of Spinal Surgery, General Hospital, Ningxia Medical University. The operative time, blood loss, length of hospital stay, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, neurological function, VAS score, vertebral Cobb angle, bone healing, and postoperative complications were compared between the 2 groups. Results: All patients were followed up for 10 to 30 (average 22) months after the operation. In the A group, operative time, blood loss, and hospital stay were less than those in the B group (P0.05). In the follow-up, the pain of patients was alleviated and nervous function was improved obviously in the 2 groups compared with pre-operation. The ESR and CRP at the 6 months after operation returned to the normal range in patients of the 2 groups. There were significant differences in the ESR and CRP among the pre-operation, the 6 months after operation, and the end of follow-up within the group (P0.05), while there were no significant differences in ESR and CRP between the 6 months after operation and the end of follow-up (P0.05). There were no significant differences in the ESR and CRP among the pre-operation, the 6 months after operation, and the end of follow-up in the 2 group (P0.05). The Cobb angles after the operation and the end of follow-up were significanthy smaller than those before the operation (P0.01), while there were no significant differences in Cobb angle before operation, after the operation, and the end of follow-up between the 2 groups (P0.05). There were no significant differences in the bone healing rate at 6 months or 1 year after operation between the A group and B group (P0.05) and the complication rate of the A group was lower than the B group (P0.01). Conclusion: Clinical efficacy of posterior intervertebral surgery is satisfatory in treating single-segment thoracolumbar spinal tuberculosis with less complications.目的：探讨后路病椎间手术治疗胸、腰椎单节段脊柱结核的临床疗效。方法：回顾性分析2010年1月至2015年1月宁夏医科大学总医院收治的胸、腰椎单节段脊柱结核患者62例的临床资料，根据手术入路方法不同，分为后路病椎间手术组和前后路联合病椎间手术组。对比分析两组的手术时间、术中出血量、住院天数、红细胞沉降率(erythrocyte sedimentation rate，ESR)、C反应蛋白(C-reactive protein，CRP)、神经功能改善情况、视觉模拟评分法(Visual Analogue Scale，VAS)评分、病变椎体Cobb角、植骨愈合情况及术后并发症。结果：62例患者均获随访，随访时间10~30(平均22)个月。后路病椎间手术组患者的手术时间、术中出血量、住院天数均短于或小于前后路联合病椎间手术组(P0.05)。两组随访过程中疼痛均较术前明显改善，末次随访时神经功能明显恢复。两组术后6个月ESR和CRP均降至正常范围，组内术前与术后6个月、末次随访的ESR和CRP比较差异有统计学意义(P0.05)，但术后6个月与末次随访的ESR和CRP间差异无统计学意义(P0.05)；组间术前、术后6个月、末次随访的ESR和CRP差异无统计学意义(P0.05)。两组患者组内术后和末次随访的Cobb角均较术前减小(P0.01)，组间术后、末次随访的Cobb角之间的差异无统计学意义(P0.05)，两组Cobb角矫正率、角度丢失之间差异无统计学意义(P0.05)。后路病椎间手术组和前后路联合病椎间手术组患者术后6个月植骨愈合率和术后1年的植骨愈合率差异无统计学意义(P0.05)。后路病椎间手术组并发症发生率明显小于前后路联合病椎间手术组(P0.01)。结论：后路病椎间手术治疗胸、腰椎单节段脊柱结核的临床疗效满意且并发症少。.

Interleukin-17 (IL-17) is closely related to osteoarthritis (OA), but animal studies that employ IL-17 to induce OA are currently lacking. Therefore, this study evaluated the effect of IL-17 in the rabbit knee joint. The right knees served as the control group. The left knees were divided randomly into 4 groups: a Hulth group and 3 IL-17 groups (1-ng, 10-ng, and 50-ng groups). OA was induced in the Hulth group using Hulth’s method. The IL-17 groups were injected with 1, 10, or 50 ng of IL-17 as indicated. Specimens were collected at 72 h, 1 week, 3 weeks, 6 weeks, and 12 weeks after surgery or the last injection. Subsequently, the following experiments were conducted: X-ray analysis, histological evaluation, and polymerase chain reaction (PCR) analysis of the mRNA expression levels of cartilage degeneration-related markers. At 12 weeks, like the Hulth group, the 10-ng and 50-ng IL-17 groups displayed typical manifestations of OA. The X-ray results, histological scores, and mRNA expression levels showed statistically significant differences between the control group and the 10-ng and 50-ng IL-17 groups. In sum, injecting 10 ng of IL-17 into the rabbit knee joint can induce OA similar to OA induced by Hulth’s method.

Background context Traditional focal debridement involves clearing of cold abscesses, caseous necrosis, residual intervertebral disc tissue, sinus tracts, bony sequestration, and inflammatory granulation. Reports have demonstrated that approximately 13% to 26% of patients were not better or relapsed after traditional focal debridement; these patients required a second surgery or prolonged antituberculous therapy. The presence of retained and diseased focal tissues requiring removal remains poorly understood. The contents of these retained tuberculous foci, improvement of surgical strategies, and improvement in spinal tuberculosis success rate are key subjects for discussion. Purpose To explain the contents of foci and explore the surgical methods and curative effect of complete debridement. Study design Retrospective study of the curative effect of treatment of thoracolumbar spinal tuberculosis by using complete debridement. Patient sample A total of 289 patients were included. Outcome measurement The outcomes were evaluated clinically by Frankel grading. The status of the anterior fusion was assessed according to the Moon standard. Eradication of infection was determined by the level of C-reactive protein and erythrocyte sedimentation rate. X-ray, computed tomography, and magnetic resonance imaging were used to evaluate disease localization and morphology. Methods A total of 289 patients with spinal tuberculosis (150 male and 139 female patients, aged 18–82; average age, 41.0±1.4 years) were included in this study. Damage to the vertebrae was as follows: 86 patients had thoracic damage, 49 had thoracolumbar damage, 125 had lumbar damage, and 47 had lumbosacral segment damage. After 2 to 4 weeks of antituberculous therapy, all patients underwent anterior debridement, deformity correction, graft fusion, and internal fixation. In this study, complete debridement was defined as the clearing of any damage or disease, including psoas abscesses, granulomas, residual intervertebral disc tissue, sinus tracts, bony sequestration, and inflammatory granulation. Tuberculosis cavities, sclerotic walls, and bony bridges that had no support and that were eroded by the foci were also removed. A total of 108 patients underwent anterior fixation with the Zephir system (Medtronic Sofamor-Danek, Minneapolis, MN, USA), Z plates (Medtronic Sofamor-Danek), or Ventrifix (China Great Wall Corporation, Beijing, China). A total of 181 patients underwent fixation, posterior correction, and one or two second anterior debridements and graft fusions. Posterior fixation, including TSRH (Medtronic Sofamor-Danek), Cotrell-Dubousset (Medtronic Sofamor-Danek), General Spinal System (WeiGao Orthopaedic Devices Company, Weihai City, China), or UPASS (WeiGao Orthopaedic Devices Company), was performed. All patients underwent structural bone grafting, including autologous iliac bone (251 patients), titanium mesh (32 patients), and rib (6 patients). Results The 289 patients were followed for 72.0±2.8 months, with 265 patients (91.69%) completely treated and 24 incompletely treated, including 3 who suspended chemotherapy because of liver or renal failure. Twenty-one patients (7.27%) failed to have a complete debridement, including 16 with incomplete bone debridement, 6 of whom underwent a second surgery, and 10 who received conservative therapy; 5 of this group had incomplete abscess debridement, 3 underwent a second surgery, and 2 received puncture aspiration of abscess under computed tomographic guidance; the second surgery rate was 3.81%. Twenty-two patients had surgery complications, including three with graft displacement, five with wound infection and fat liquefaction, four with pleural effusion, six with pain at the graft harvesting site, and four with incisional hernia. Bone graft healing was observed 4.3±1.2 months after surgery. The Cobb angle before and after surgery and at the final follow-up was 22.16±11.51°, 8.11±4.83°, and 9.96±3.49°, respectively, with a mean correction of 63.40% after surgery; however, a 1.85±1.34° loss was observed at the final follow-up with loss rate of 8.35%. Conclusions Sclerotic bone, multiple cavities, and bony bridges are foci in spinal tuberculosis. Clearing tuberculous foci, sclerotic bone, multiple cavities, and bony bridges to increase the curative effect is an effective treatment method.

Background context Tumor necrosis factor-α (TNF-α) is a regulatory cytokine that can increase the activity of enzymes such as ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which degrade disc matrix. ADAMTS are enzymes that break down disc matrix and thereby mediate disc degeneration. Bone morphogenetic protein-7 (BMP-7), on the other hand, stimulates synthesis of the disc extracellular matrix and is a potential therapeutic molecule for the treatment of disc degeneration. However, the effects of BMP-7 on TNF-α and ADAMTS are unknown. Purpose We investigated the effects of BMP-7 on the catabolic regulators such as TNF-α and ADAMTS and evaluated the molecular mechanism by which BMP-7 affects the catabolic regulators. Study design This was an in vitro study in which we used human intervertebral disc cells cultured in alginate beads. Methods Human intervertebral disc cells were cultured in alginate beads, and treated with TNF-α, or TNF- α plus BMP-7, pharmacological inhibitor of ERK1/2 (U0126), p38 (SB203580), or NFκB (BAY 11-7082). The mRNA levels of target genes were measured by real-time polymerase chain reaction, and the protein levels were determined by the Western blots. The nuclear factor (NF)κB activity was analyzed by measured phosphorylation and nuclear translocation of the NFκB protein p65. Results TNF-α activated NFκB signaling and induced up-regulation of the catabolic regulators ADAMTS-4 and ADAMTS-5, contributing to degradation of the disc matrix macromolecules aggrecan and collagen II. BMP-7 antagonized the TNF-α–induced activation of NFκB protein p65 and blocked TNF-α–induced up-regulation of ADAMTS-4 and ADAMTS-5, leading to reversing TNF-α–mediated degradation of aggrecan and collagen II. Moreover, BMP-7 antagonized the TNF-α–induced activation of NFκB signaling by suppressing phosphorylation and nucleus translocation of NFκB protein p65. Conclusion BMP-7 antagonizes TNF-α–induced activation of NFκB and up-regulation of ADAMTS, leading to decreased degradation of disc matrix macromolecules. These data indicate that BMP-7 has a dual mechanism of action on disc metabolism: (1) the previously well-described positive effect on disc matrix synthesis and (2) an anticatabolic effect that is described here. This understanding is important as BMP-7 is being considered for treatment of disc degeneration.

Icariin (ICA) and phosphorylated icariin (pICA) have excellent antiviral and antioxidant effects. However, whether ICA and pICA cause anti-LPS-induced intestinal damage remains unclear. In this study, we used Caco-2 cells as a model to investigate the protective effects of ICA and pICA on human colonic epithelial cells and explore their potential mechanisms. Our results indicated that ICA and pICA increased cell viability and decreased lactate dehydrogenase activity in Caco-2 cells. ICA and pICA also attenuated LPS-induced changes in intestinal epithelial cell permeability and reduced the levels of oxidative stress indicators, such as reactive oxygen species, malondialdehyde, and hydrogen peroxide, in Caco-2 cells. Antioxidant indicators, such as superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity, were increased, while the levels of IL-1β, IL-6, IL-8 and TNF-α were reduced in the ICA and pICA groups. Furthermore, ICA and pICA decreased the gene abundance and enzyme activities of caspase-3, -8, -9 and -10 in Caco-2 cells. Our data suggest that ICA and pICA effectively attenuated LPS-induced changes in the oxidative stress, inflammation, apoptosis and intestinal permeability of intestinal epithelial cells. These findings provide new insight for treating LPS-induced intestinal injury.

Extrapedicular infiltration anesthesia (EPIA) was reported for percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) and provided good local anesthetic effects. Because of differences in anatomical morphology at each lumbar level, the puncture method of EPIA is not uniform in each lumbar vertebrae. To accurately insert the anesthetic needle into the extrapedicular region, we researched the puncture method of EPIA at each lumbar level. We retrospectively analyzed computed tomography (CT) images in 230 patients with lumbar osteoporotic fractures, including 59 L1 fractures, 54 L2 fractures, 50 L3 fractures, 36 L4 fractures, and 31 L5 fractures. The puncture of EPIA was simulated in every fractured vertebrae through CT, and the skin puncture point, puncture direction, and puncture depth of the anesthetic needle were observed. These specific parameters were the distance from the skin puncture point to the superior border of the pedicle projection on the skin (distance AD), distance from the skin puncture point to the lateral border of the pedicle projection on the skin (distance BC), sagittal section angle (SSA), transverse section angle (TSA), and depth of EPIA. As the lumbar ordinal number increased, the SSA, distance AD, TSA, and distance BC for each lumbar level gradually increased, and the puncture depth gradually decreased, all these parameters showed significant differences among the 5 lumbar levels (P

Background The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA). Methods MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017 for eligible randomized controlled studies. Results Thirty-two randomized controlled studies were included. LMWH provided better protection against VTE than placebo. In both TKA and THA patients, the rates of VTE were lower with factor Xa inhibitors than LMWH. In THA patients, the rate of deep vein thrombosis (DVT) was lower with factor Xa inhibitors than LMWH. In TKA patients, the rates of VTE and DVT were similar between LMWH and direct thrombin inhibitors. In THA patients, the rate of VTE was lower with direct thrombin inhibitors than with LMWH, while the DVT rates were similar. The pulmonary embolism rates were similar between all 3 classes of drugs in TKA and THR patients, as were the major bleeding rates. Nonmajor and minor bleeding rates were also similar between the 3 drug classes. Conclusion LMWH is associated with a higher rate of VTE than factor Xa inhibitors in TKA and THA patients. Direct thrombin inhibitors are associated with a lower rate of VTE in THA patients, but their effectiveness with respect to DVT and pulmonary embolism prophylaxis is similar to that of LMWH in TKA and THA patients.

The rapid development of complexity and intelligence in manufacturing systems leads to an increase in potential operational risks and therefore requires a more comprehensive system-level health diagnostics approach. Based on the massive multi-source operational data collected by smart sensors, this paper proposes a mission reliability-driven manufacturing system health state evaluation method. Characteristic attributes affecting the mission reliability are monitored and analyzed based on different sensor groups, including the performance state of the manufacturing equipment, the execution state of the production task and the quality state of the manufactured product. The Dempster-Shafer (D-S) evidence theory approach is used to diagnose the health state of the manufacturing system. Results of a case study show that the proposed evaluation method can dynamically and effectively characterize the actual health state of manufacturing systems.

Statins are the most effective drugs used in the reduction of intracellular synthesis of cholesterol. Numerous studies have confirmed that statins reduce the risk of multiple types of cancers. Statin use in cancer patients is associated with reduced cancer-related mortality. Epithelial-to-mesenchymal transition (EMT), a complicated process programmed by multiple genes, is an important mechanism of cancer metastasis. We explored the effect and mechanism of atorvastatin on the EMT process in A549 cells by establishing an EMT model in vitro induced by TGF-β1, and evaluated the effects of atorvastatin on the lower signaling pathway of TGF-β1 stimulation. Our results showed that atorvastatin partially inhibited the EMT process, and inhibited cell migration and actin filament remodeling. Transcriptional upregulation of ZEB1 and protein sphingosine kinase 1 (SphK1) induced by TGF-β1 was also suppressed. SphK1 plasmid transient transfection strengthened the EMT process induced by TGF-β1 in the presence of atorvastatin. Our experiments confirmed that atorvastatin can partially inhibit the EMT process of non-small cell lung cancer cells induced by TGF-β1 by attenuating the upregulation of SphK1.

The routine surgical approach to posterior reconstruction in spinal tuberculosis is short- or long-segment fixation and/or fusion. This method sacrifices movement at more than one vertebral level, limits normal movement of the spinal column, and leads to degeneration of the small joints of the adjacent levels. Surgical techniques that reduce the number of fixed vertebral levels and maximize the retention of movement of the spinal column are of current interest in the treatment of spinal tuberculosis. A total of 106 patients with lumbosacral tuberculosis were randomly divided into two groups: a single-segment fixation group and a short-segment fixation group. After posterior correction and internal fixation, all patients underwent anterior radical debridement and interbody fusion with bone grafting. The mean postoperative follow-up period was 58.09 ± 17.01 months. The average bone graft healing time was 4.35 ± 1.04 months in the single-segment group and 4.47 ± 1.10 months in the short-segment group. In the single-segment group, correction of the Cobb angle was 14.47 ± 3.76° and the loss rate was 7.22 %, and in the short-segment group, correction of the Cobb angle was 16.20 ± 2.70° and the loss rate was 6.37 % (P

Traditionally, bacterial cultures serve as the gold standard for the detection of drug resistance and can provide evidence for directing the treatment of tuberculosis. However, this method has a low positive rate and is time consuming, which significantly limits its wide application. Thus, in the present study, the genes associated with drug resistance were amplified and sequenced to determine the presence of drug-resistant mutations in Mycobacterium tuberculosis. In addition, to find a more sensitive, specific, rapid, and simple method for the detection of drug-resistant bacteria, this method was compared with traditional bacterial culture.Pus was collected from surgical patients with spinal tuberculosis. The common drug resistance genes (rpoB, rpsL, and katG) were amplified by PCR. The PCR products were then sequenced, and the sequences were compared with those in the NCBI database using DNATools v.5.1 software.Mutations were identified in 17 patients, including mutations in the rpsL gene in four patients, the rpoB gene in seven, and the katG gene in six. The mean time of detection was 6 days.These results indicated that PCR and DNA sequencing are rapid, sensitive, and specific methods for the detection of drug-resistant genes of M. tuberculosis in patients with spinal tuberculosis. This method may provide critical evidence for the clinical treatment of tuberculosis when it is applied in combination with bacterial culture.

A retrospective study was conducted to determine the beneficial effect of posterior mono-segmental fixation, combined with anterior debridement and strut graft for the treatment of mono-segmental lumbar spine tuberculosis.From February 2002 to February 2008, a total of 34 cases with mono-segmental lumbar spine tuberculosis were treated by posterior mono-segmental fixation, combined with anterior debridement and strut graft. The degree of damage to the patients' vertebral bodies was 1/3-2/3 height. Antituberculous therapy was performed both before and after surgery.None of the patients suffered from spinal cord, nerve, great vessel or organ damage, with all patients passing through the peri-operative period successfully. Graft union was observed four to six months after surgery, with a mean of five months. In addition, no fracture or prolapsed internal fixation was found. The Cobb's angle prior to and after surgery, and at the final follow-up were 22.70 ± 9.8°, 4.5 ± 8.4° and 5.30 ± 7.10°, respectively, with a mean correction of 18.20 ± 5.8° after surgery; however, 1.70 ± 1.0° loss was observed at the final follow-up. Four cases with neurological lesions recovered to 'E' grade. At the final follow-up, all patients could live and work normally.The results demonstrated that for cases with 1/3-2/3 height of vertebral body damaged in mono-segmental lumbar spine tuberculosis, treatment with posterior mono-segmental fixation, combined with anterior debridement and strut graft, can cure foci, rebuild spinal stability, reduce fused segments, and retain maximal function of the motion units.

The purpose of this study was to assess the clinical efficacy of intervertebral focal surgery by complete debridement, deformity correction, graft fusion, and internal fixation for patients with non-contiguous multifocal spinal tuberculosis.A total of 29 cases with non-contiguous multifocal spinal tuberculosis admitted to the hospital from January 2000 to January 2007 were treated by intervertebral focal surgery. There were 63 foci in 29 cases, averaging 2.2 foci per case, and 146 affected vertebral bodies, averaging 2.3 vertebral bodies per focus. Three cases had one normal intervertebral disc between two foci, and the other 26 cases had two or more normal intervertebral discs between two foci.All cases were followed-up for an average of five years. The kyphosis showed a mean correction rate of 67.7% after surgery. A mean loss rate of correction of 8.2% was observed at the final follow-up. The levels of erythrocyte sedimentation rate and C-reactive protein returned to normal in 27 cases on average at 5.8 months and bone union could be observed at five months after surgery. Eleven cases with nerve damage recovered to E grade at the final follow-up.Intervertebral focal surgery by complete debridement, deformity correction, graft fusion, and internal fixation for patients with non-contiguous multifocal spinal tuberculosis was feasible and effective.

In this article, we aim to study the influence of matching degrees of synchronous natural auditory and visual information on cognitive integration. Videos with matched, moderately matched, and mismatched audio-visual information were used as stimuli. The results showed that videos with moderately matched audio-visual information could elicit N400, P600, and late negativity (LN) effects, while videos with mismatched audio-visual information could elicit N400 and late negativity effects as compared with those with matched audio-visual information. It was further proven that N400 might reflect the connection process during multisensory integration, and P600 was more related to the evaluation process on the matching degrees of the audio-visual information in videos. Late negativity under the mismatched condition might be the combination of late frontal negativity (LFN) and late posterior negativity (LPN), which reflected the attention reallocating process and the recognition process, while late negativity under the moderately matched condition might be the LPN, which was related to the recognition process in the human brain. It was demonstrated that cognitive integration of synchronous audio-visual information would be modulated by different matching degrees of audio-visual information as indexed by different event-related potential (ERP) effects.

In this paper, we aimed to study the semantic association of ecologically unrelated synchronous audio-visual information in cognitive integration. A moving particle, which speed varied, was taken as a visual stimulus, while a simple tone, which frequency varied, was used as an auditory stimulus, both were synchronously presented to subjects in the form of a video. Behavioral results confirmed our hypothesis that the moving particle with varied speed and the simple tone with varied frequency were highly associated. Event-related potential (ERP) results showed that an N400 effect and a late posterior negativity (LPN) were elicited under the Incongruent condition as compared to the Congruent condition. It was further determined that there was semantic association between ecologically unrelated synchronous audio-visual information in cognitive integration. We considered that the N400 effect in our results reflected the process that stimulus-driven activities are bound together through a temporal semantic network (TSN) to form multimodal representations, while the state of this temporal semantic network was determined by both long-term learned association among stimuli and short-term experience of incoming information. The LPN might reflect the process that the human brain searches and retrieves context-specifying information in order to make a judgment, and the context-specifying information might have originated from the long-term learned association stored in the brain.

Background context The ultrashort-course chemotherapeutical scheme of less than 6 months has been used for part of patients with pulmonary tuberculosis and satisfactory curative effects have already been achieved. However, few systematic and clinical reports so far about medical treatment of spinal tuberculosis by using ultrashort-course chemotherapeutical schemes have been published in the spine-care literature. Purpose To assess the results of ultrashort-course chemotherapy (UCC) in conjunction with partial excision of pathological vertebrae for spinal tuberculosis. Study design/setting This is a retrospective comparative study of case series from a single center. Patient sample Seventy-six cases of spinal tuberculosis, treated during 1998 and 2003 by senior author, were reviewed. All the cases underwent chemotherapies in conjunction with the uniform partial excision of pathological vertebra and had a minimum follow-up of 2 years. Outcome measures Clinical manifestations, laboratory tests, imaging examination, examination by ultrasonic wave B, drug complications, and clinical effects based on the previously described evaluative measures. Methods Of the 76 cases, 28 had UCC with the scheme of 2SHRZ/2.5H2R2Z2, 23 had short-course chemotherapy (SCC) with the scheme of 3SHRZ/5H2R2Z2, and 25 had standard chemotherapy (SC) with the scheme of 3SHRZ/9H2R2Z2. All the patients had anterior partial excisions of pathological vertebrae, large iliac strut graft, and anterior or posterior fixation. The mean time of follow-up surveys for the ultrashort-course, short-course, and standard chemotherapy cases was 42.3 m, 46.5 m, and 55.4 m, respectively. Results The observance indices included 1) clinical manifestations: disappearance of tuberculosis symptoms, no CC pains, recovery of normal life or work, no percussion pains on pathologic sites, and recovery of neural functions; 2) laboratory tests: normal or close to normal test results of both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) or one of them; 3) imaging examinations: X-ray films, computed tomography scan, and magnetic resonance imaging examinations show disappearance of abscesses, no new destructive foci, bone union on the bone grafting interface, satisfactory correction of deformities, and less than 5° of the angle loss of deformity corrections; 4) examination by ultrasonic wave B: no opaque dark area of fluid sonolucent areas identified in possible sites of paravertebral abscesses or gravitation abscesses; and 5) drug complications: hepatic and renal functions, nervus vestibularis lesion, and gastrointestinal tract reactions. All the cases met the protetrakis indices and obtained complete clinical cure of spinal tuberculosis in the last follow-up. The significant differences of major drug complications were found among the 3 groups, with 5 cases of UCC (18%), 15 cases of SCC (65%), and 19 cases of SC (76%).The lasting chemotherapeutic lesion of liver, kidney, or the permanent nervus vestibularis lesion were found 3 cases in SCC, 5 cases in SC, and no case in UCC group. Conclusions No significant differences in clinical cure rate were found among 3 groups. UCC in conjunction with anterior partial excisions of pathological vertebrae, large iliac strut graft, and anterior or posterior internal instrumental fixation achieved excellent clinical results and the lowest complication rate of antituberculosis chemotherapy.

We screened 117 breast tumour samples in Chinese females for mutations in the breast cancer 1 ( BRCA1) gene and identified a novel mutation in the 5′ untranslated region (5′ UTR) in two patients with grade III infiltrating ductal breast carcinoma. We examined whether this 5′ UTR mutation affected the translational efficiency of BRCA1 protein. A vector was constructed containing the mutated 5′ UTR up-stream of luciferase and we compared its translational efficiency with a wild-type 5′ UTR. The expression of BRCA1 protein in breast tumour samples was evaluated using immunohistochemistry. The mutated 5′ UTR of BRCA1 resulted in less luciferase activity compared with the wild-type 5′ UTR, while there were no significant differences in luciferase mRNA levels. BRCA1 protein was much less expressed in breast tumour tissue from patients with the 5′ UTR mutation than in samples from patients without the mutation. Our results show that a mutation in the 5′ UTR of the BRCA1 gene downregulates translational efficiency of the protein.

Therapeutic vaccines to induce anti-tumor CD8 T cells have been used in clinical trials for advanced melanoma patients, but the clinical response rate and overall survival time have not improved much. We believe that these dismal outcomes are caused by inadequate number of antigen-specific CD8 T cells generated by most vaccines. In contrast, huge CD8 T cell responses readily occur during acute viral infections. High levels of type-I interferon (IFN-I) are produced during these infections, and this cytokine not only exhibits anti-viral activity but also promotes CD8 T cell responses. The studies described here were performed to determine whether promoting the production of IFN-I could enhance the potency of a peptide vaccine. We report that cyclic diguanylate monophosphate (c-di-GMP), which activates the stimulator of interferon genes, potentiated the immunogenicity and anti-tumor effects of a peptide vaccine against mouse B16 melanoma. The synergistic effects of c-di-GMP required co-administration of costimulatory anti-CD40 antibody, the adjuvant poly-IC, and were mediated in part by IFN-I. These findings demonstrate that peptides representing CD8 T cell epitopes can be effective inducers of large CD8 T cell responses in vaccination strategies that mimic acute viral infections.

STUDY DESIGN An in vitro study using human intervertebral disc cells. OBJECTIVE To evaluate the effect of link protein peptide (LPP) on the expression of disc extracellular matrix macromolecules sulfated glycosaminoglycan, aggrecan, and collagen II. To determine the effect of LPP on catabolic regulators and to compare LPP with both BMP2 and BMP7 in terms of osteoinductivity. SUMMARY OF BACKGROUND DATA Previous studies have shown that N-terminal link-protein peptide (LPP) can induce synthesis of proteoglycans and collagen II in cartilaginous cell types. However, the effect of LPP on human disc cells remains to be investigated. Moreover, the effects of LPP on the catabolic regulators and the osteoinductive potential of LPP are unknown. METHODS Human intervertebral disc cells were cultured in alginate beads and treated with LPP, truncated LPPs, and the reverse sequence of LPP (LPR). The levels of aggrecan and collagen II mRNAs were measured by real-time polymerase chain reaction. Sulfated glycosaminoglycan content was assayed using the dimethylmethylene blue method. The protein levels of collagen II and catabolic regulators were determined by enzyme-linked immunosorbent assays and Western blots. The relative osteoinductive potential of LPP was evaluated by comparing the effect of LPP, BMP2, and BMP7 on in vitro markers of osteoinductivity. RESULTS LPP upregulates expression of aggrecan and collagen II at both mRNA and protein levels. The full length of LPP is required for this upregulation. Neither the reverse sequences of LPP nor the truncated LPPs were as effective as the full-length LPP. LPP selectively inhibits expression of the catabolic regulators interleukin (IL)-1β and MMP1 and has no effect on expression of the other catabolic regulators tumor necrosis factor α, ADAMTS1, ADAMTS4, ADAMTS5, MMP3, and MMP9. LPP has relatively little osteoinductive effect compared with BMP2 and BMP7. CONCLUSION LPP could have value in stimulating the growth and regeneration of degenerated discs with less concern of creating unwanted bone. LEVEL OF EVIDENCE N/A.

Study design A retrospective clinical study of 19 cases of ossification of ligamentum flavum (OLF) in Chinese population. Objective To inspect the epidemiology, clinical presentation, pathology, radiologic findings, and treatment outcome in 19 Chinese patients of OLF at a single institution. Summary of background data OLF in the thoracic region causing neurological impairment is a rare pathologic entity described mainly in Japanese literature. The present study represents a series of Chinese patients with OLF at the thoracic spine. Methods Nineteen patients (7 male and 12 female; ages ranging between 39 and 73 y) were included in this study. All patients have been treated by posterior thoracic extensive decompressive laminectomy. Neurological status was evaluated using the Japanese Orthopedic Association (JOA) score, the recovery rate, and the Oswestry Disability Index (ODI) before and after surgery. Patients' pain relief was evaluated using a visual analog scale (VAS) pain score. Results Mean JOA score was 3.16±1.05 before surgery to 8.34±3.28 after surgery. Mean recovery rate was 61.4%±32.5%. Mean ODI scores had significantly decreased from 66.36%±10.91% before surgery to 25.45%±12.19% after surgery. The result of VAS score were 6.29±1.83 before the operation and 2.18±1.90 at final follow-up. All patients improved at the end of the evaluation period. There was no recurrence. Conclusions Early diagnosis and sufficient surgical treatment play key roles in improving functional outcomes. Posterior thoracic extensive decompressive laminectomy gives satisfactory results and leads to significant clinical improvement.