Poor bone mineral density aggravates adjacent segment's motility compensation in patients with oblique lumbar interbody fusion with and without pedicle screw fixation: An in silico study.

Objective: Motility compensation increases the risk of adjacent segment diseases (ASDs). Previous studies have demonstrated that patients with ASD have a poor bone mineral density (BMD), and changes in BMD affect the biomechanical environment of bones and tissues, possibly leading to an increase in ASD incidence. However, whether poor BMD increases the risk of ASD by aggravating the motility compensation of the adjacent segment remains unclear. The present study aimed to clarify this relationship in oblique lumbar interbody fusion (OLIF) models with different BMDs and additional fixation methods. Methods: Stand-alone (S-A) OLIF and OLIF fixed with bilateral pedicle screws (BPS) were simulated in the L4-L5 segment of our well-validated lumbosacral model. Range of motions (ROMs) and stiffness in the surgical segment and at the cranial and caudal sides' adjacent segments were computed under flexion, extension, and unilateral bending and axial rotation loading conditions. Results: Under most loading conditions, the motility compensation of both cranial and caudal segments adjacent to the OLIF segment steeply aggravated with BMD reduction in S-A and BPS OLIF models. More severe motility compensation of the adjacent segment was observed in BPS models than in S-A models. Correspondingly, the surgical segment's stiffness of S-A models was apparently lower than that of BPS models (S-A models showed higher ROMs and lower stiffness in the surgical segment). Conclusion: Poor BMD aggravates the motility compensation of adjacent segments after both S-A OLIF and OLIF with BPS fixation. This variation may cause a higher risk of ASD in OLIF patients with poor BMD. S-A OLIF cannot provide instant postoperative stability; therefore, the daily motions of patients with S-A OLIF should be restricted before ideal interbody fusion to avoid surgical segment complications.

Design of LiFePO4 and porous carbon composites with excellent High-Rate charging performance for Lithium-Ion secondary battery.

Lithium iron phosphate (LFP) is one of the promising cathode materials of lithium ion battery (LIB), but poor electrical conductivity restricts its electrochemical performance. Carbon coating can improve electrical conductivity of LFP without changing its intrinsic property. Uniform coating of carbon on LFP is significant to avoid charge congregation and unpreferable redox reactions. It is the first time to apply the commercial organic binder, Super P® (SP), as carbon source to achieve uniform coating on LFP as cathode material of LIB. The simple and economical mechanofusion method is firstly applied to coat different amounts of SP on LFP. The LIB with the cathode material of optimized SP-coated LFP shows the highest capacity of 165.6 mAh/g at 0.1C and 59.8 mAh/g at 10C, indicating its high capacity and excellent high-rate charge/discharge capability. SP is applied on other commercial LFP materials, M121 and M23, for carbon coating. Enhanced high-rate charge/discharge capabilities are also achieved for LIB with SP-coated M121 and M23 as cathode materials. This new material and technique for carbon coating is verified to be applicable on different LFP materials. This novel carbon coating method is expected to apply on other cathode materials of LIB with outstanding electrochemical performances.

[Mechanism of Duhuo Jisheng decotion in delaying degeneration of nucleus pulposus cells in human intervertebral disc].

This paper aimed to investigate the role of Duhuo Jisheng decotion (DHJSD) in delaying human disc degeneration and its possible molecular mechanism. The intervertebral disc specimens were divided into normal and degenerated groups according to Pfirrmann classfication. The expressions of TNF-α, IL-1ß, MMP-3 and MMP-13 in intervertebral disc tissue were detected by Western blot and PCR. Then degenerated human primary NPCs were cultured in vitro, the viability of NPCs treated with stromal cell-derived factor-1 (SDF-1，10 µg·L⁻¹)and various concentrations of DHJSD was assessed by the CCK-8 assay, and the appropriate concentration was screened. The experiment was divided into three groups, control group, SDF-1 group and DHJSD plus SDF-1 group. The levels of TNF-α, IL-1ß, Agg, coIⅡ, MMP-3 and MMP-13 were detected. The levels of CXCR4, NF-κB major groups P65 phosphorylation (p-P65) and nuclear translocation, after treated with CXCR4 siRNA and NF-κB inhibitor (BAY11-7082) were measured by Western blot and immunofluorescence. At the same time, the expression of cell inflammatory factors and extracellular matrix were also measured. The expressions of TNF-α, IL-1ß, MMP-3 and MMP-13 in the degenerated intervertebral disc tissue were significantly increased. In vitro study, the results of CCK-8 indicated that the viability of NPCs was significantly increased when DHJSD concentration was 300 mg·L⁻¹. After the experiment was divided into three groups, compared with SDF-1 group, the expressions of TNF-α, IL-1ß, MMP-3 and MMP-13 in DHJSD group were significantly decreased, but the expressions of Agg, coIⅡ were significantly increased. When CXCR4-siRNA was transfected into NPCs, SDF-1 increased expressions of CXCR4 and p-P65 and inhibited nuclear translocation of P65, whose effect was suppressed by CXCR4-siRNA and DHJSD. In addition, when BAY11-7082 was used to treat NPCs, the expression of TNF-α, IL-1ß, MMP-3 and MMP-13 were significantly decreased. DHJSD could inhibit the production of inflammatory factors and promote the synthesis of extracellular matrix. The potential mechanism may be related to the SDF-1/CXCR4/NF-κB signaling pathway.

Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway.

Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 µg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.

Efficacy of Mycobacterium vaccae immunotherapy for patients with tuberculosis: A systematic review and meta-analysis.

Tuberculosis (TB) is a significant cause of illness and death worldwide. Immunotherapy has been investigated in the treatment of TB. The purpose of this study was to perform a meta-analysis investigating the effectiveness of the M. vaccae vaccine. Medline, Cochrane, EMBASE, and Google Scholar were searched until November 5, 2015 using the keywords: tuberculosis, pulmonary TB, therapeutic vaccines, immunotherapy, M. vaccae, sputum smear. Randomized controlled trials (RCTs) or 2-arm prospective studies were included. The primary outcome was the sputum smear clearance rate at 1 or 2 months and 6 months after treatment. Secondary outcomes were improvement of chest X-ray findings, sputum culture negative rate at 1 or 2 months and 6 months, erythrocyte sedimentation rate (ESR), hemoglobin, and leukocyte count, weight gain, and mortality. Of 89 records identified, 13 RCTs were included in the meta-analysis. The number of patients ranged from 22 to 1337, and the mean age ranged from 26.4 to 44.3 y. Patients treated with M. vaccae were more likely to have negative sputum smear results at 1-2 months (pooled OR = 2.642, 95% CI: 1.623-4.301, P < .001) and at 6 months (pooled OR = 2.111, 95% CI: 1.141-3.908, P = .017), and have a negative sputum culture at 1 or 2 months (pooled OR = 2.660, 95% CI: 1.978-3.578, P < .001). The results of this meta-analysis suggest that M. vaccae immunotherapy may be effective in the treatment of pulmonary TB.

Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice.

Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury.

ACE/ACE2 ratio and MMP-9 activity as potential biomarkers in tuberculous pleural effusions.

OBJECTIVE: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. EXPERIMENTAL DESIGN: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). RESULTS: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. CONCLUSION: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.

The effects of anti-P-selectin antibody on leucocyte activity related to cigarette smoke in rats.

Nicotine-induced expression of P-selectin is implicated in endothelial cell damage related to smoking. Thirty male Sprague-Dawley rats were divided into three groups: two experimental and one control. Both experimental groups were exposed to cigarette smoke for four weeks, but one group was also given anti-P-selectin antibody (100 microg IgG per 100 g body weight) intravenously. Rolling and adhesion leucocytes within the microcirculation of the cremaster muscle were measured. The urine cotinine concentrations of rats exposed to smoke were 612 ng/ml higher than those of non-smokers. Both rolling and adherent leucocytes were highest and steady in the group given anti-P-selectin antibody at about 50 and 10, respectively. There was a significant drop in both rolling and adherent leucocytes (31 to 4 and 5 to 2) after the anti-P-selectin antibody had been given. However, this effect was short-lived as both increased above those at 35 minutes by 120 minutes (p<0.001). The increase in leucocyte rolling and adherence caused by smoking can be lowered by giving anti-P-selectin antibody. The effective period in rats was two hours, with the maximal effect one hour after injection.