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Rationale: The spine is one of the most common metastatic sites of non-small cell lung cancer (NSCLC), and NSCLC spinal metastasis results in serious consequences. Metastatic extravasation of disseminated cancer cells including increased invasiveness, adhesion and transendothelial migration is crucial for tumor metastasis. This study aimed to investigate the mechanisms underlying NSCLC spinal metastasis based on the C-X3-C motif chemokine ligand 1- (CX3CL1) and intercellular adhesion molecule-1- (ICAM-1) mediated signaling network. Methods: Immunohistochemistry, western blotting, and reverse transcription-quantitative PCR were conducted to detect the distribution of CX3CL1/ICAM-1 in different organs. Transwell, adhesion, and transendothelial migration assays were performed to evaluate the regulatory effects of CX3CL1/ICAM-1 on NSCLC cell invasion, adhesion, and transendothelial migration in vitro. A spontaneous spinal metastasis mouse model was established via injection of NSCLC cells into the left cardiac ventricle of NOD/SCID mice. The effects of CX3CL1/ICAM-1 on NSCLC spinal metastasis in vivo were validated using bioluminescent, micro-computerized tomography, immunohistochemistry and histological analyses. Results: CX3CL1 expression was specifically higher in vertebral bone compared with limb bones and lung tissue, and was associated with NSCLC spinal metastasis. Mechanically, vertebral bone marrow endothelial cells (VBMECs) enhanced NSCLC cell invasion via CX3CL1 signaling-mediated activation of the PI3K/AKT pathway. Furthermore, we found that VBMECs effectively induced ICAM-1-dependent NSCLC cell adhesion in coordination with platelets through the CX3CL1/ICAM-1/LFA-1 pathway. Meanwhile, CX3CL1 enhanced NSCLC cell transendothelial migration by increasing permeability of VBMECs via ICAM-1-dependent activation of the Src/GEF-H1 pathway. Interestingly, NSCLC cells were indicated to promote CX3CL1 secretion of VBMECs through MAPK14/ADMA17-dependent CX3CL1 release and NF-κB-dependent CX3CL1 synthesis. Based on these findings, we revealed a novel feedback cycle between circulating NSCLC cells and VBMECs mediated by CX3CL1/ICAM-1 signaling. Further disengagement of the CX3CL1/ICAM-1-mediated feedback cycle in vivo significantly restricted metastasis and prolonged mouse survival. Conclusions: Our results indicated a unique feedback cycle between circulating NSCLC cells and VBMECs mediated by CX3CL1/ICAM-1 signaling, which is necessary for NSCLC spinal metastasis. This work provides a new perspective for underlying the mechanisms of NSCLC spinal metastasis and indicates potential novel targets for the prevention of NSCLC spinal metastasis.

The present study aimed to establish an animal model of the osteofascial compartment syndrome (OFCS) in hind legs of rabbits, and to repair an early nerve injury using the self-polymerized peptide nanofiber material that was laced with nerve growth factors (NGFs). An animal model of the compartment syndrome was established using the tourniquet method. The intrafascial pressure of rabbit legs at different time points was measured after successful modeling. Western blotting was used to assess the proliferation of nerve cells after injury. After incision and decompression, the repair group was implanted with the self-polymerized peptide nanofiber material in combination with NGFs at the nerve injury sites for repair of the injured nerves. Rabbit hind leg nerve specimens were collected from experimental rabbits (control group), rabbits 5 days after injury (unrepaired group), and rabbits 5 days after injury (repaired group), and hematoxylin-eosin (HE) staining analysis and immunofluorescence experiments were also performed. After loosening the tourniquet, the intra-fascial pressure peaked on the 1st day after injury and then gradually decreased. A western blot showed low expression of the proliferating cell nuclear antigens (PCNAs) in the control group, as it began to increase 4 h after injury, peaked 5 days after injury (P < 0.05), and then gradually decreased. Meanwhile, the tissue morphology of the repair group was better than that of the non-repair group. Fluorescence double labeling results showed that the proliferation of nerve cells in the repair group increased significantly, and S100 and DAPI co-labeling intensities increased significantly. The early application of the self-polymerizing peptide nanofiber material combined with NGF exhibited evident effects on the nerve injury treatment in the osteofascial compartment syndrome.

Numerous studies have shown that cervical arthrodesis is associated with the adjacent-segment pathology (ASP), such as adjacent-level ossification development (ALOD). However, it still remains largely unclear whether the self-locking stand-alone implant system can reduce the incidence of ALOD. In the present study, we prospectively recruited 120 patients with cervical degenerative disc disease (CDDD) who were treated by anterior cervical discectomy and fusion (ACDF). These patients were randomly and evenly divided into the ROI-C group and plate group. Clinical and radiologic follow-up was performed at 3, 6, 12, 24 and 36 months after surgery. Clinical evaluation included preoperative and postoperative assessments of Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) score. The presence and severity of ALOD, as well as the C2-7 Cobb angle, were assessed on the lateral cervical films during follow-up. There were no significant differences in JOA and NDI scores at each time point during the follow-up period between the two groups. ALOD occurred in 8.8% of 58 patients and 6.7% of 104 levels in the cage group. Moreover, ALOD occurred in 20.1% of 57 patients and 17.8% of 101 levels in the plate group. The ALOD was more serious in the plate group compared with the cage group. The C2-7 Cobb angle was significantly improved compared with that before the operation and could be maintained during the follow-up in both groups. The self-locking stand-alone cage was efficacious for ACDF, and it could reduce the incidence of ALOD compared with anterior plate and cage.

Immune checkpoint inhibitors (ICIs) have made breakthrough progress in the treatment of various malignant tumors. However, only some patients receiving ICIs obtain long-lasting clinical effects, and some patients still do not achieve remission. Improving the treatment benefits of this part of the population has become a concern of clinicians. IL-1 signaling plays an important role in the tumor microenvironment (TME). However, the relationship between the IL-1 signaling mutation status and the prognosis of colon adenocarcinoma (COAD) patients receiving ICIs has not been reported. We downloaded the data of a COAD cohort receiving ICIs, including prognostic data and mutation data. Additionally, we downloaded the data of a COAD cohort from The Cancer Genome Atlas (TCGA) database, including clinical data, expression data and mutation data. Gene set enrichment analysis (GSEA) was used to assess differences in the activity of some key physiological pathways between the IL-1 signaling mutated-type (IL-1-MT) and IL-1 signaling wild-type (IL-1-WT) groups. The CIBERSORT algorithm was used to evaluate the contents of immune cells in the TME of COAD patients. The multivariate Cox regression model results suggested that IL-1-MT can be used as an independent predictor of a better prognosis in COAD patients receiving ICIs (P = 0.03, HR = 0.269, 95% CI: 0.082-0.883). Additionally, IL-1-MT COAD patients had significantly longer overall survival (OS) (log-rank P = 0.015). CIBERSORT analysis showed that the IL-1-MT group had high infiltration levels of activated dendritic cells (DCs), M1 macrophages, neutrophils, activated natural killer (NK) cells, activated CD4+ memory T cells and CD8+ T cells. Similarly, the IL-1-MT group had significantly upregulated immunogenicity, including in terms of the tumor mutation burden (TMB), neoantigen load (NAL) and number of mutations in DNA damage repair (DDR) signaling. GSEA showed that the IL-1-MT group was highly enriched in the immune response and proinflammatory mediators. Additionally, the expression levels of immune-related genes, immune checkpoint molecules and immune-related signatures were significantly higher in the IL-1-MT group than in the IL-1-WT group. IL-1-MT may be an independent predictor of a good prognosis in COAD patients receiving ICIs, with significantly longer OS in IL-1-MT COAD patients. Additionally, IL-1-MT was associated with significantly increased immunogenicity, activated immune cell and inflammatory mediator levels and immune response-related scores.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in tumor metastasis. The aim of the present study was to investigate their expression profile and potential functions in spinal metastasis (SM) of lung adenocarcinoma. METHODS: We conducted lncRNA and mRNA expression in lung adenocarcinoma and its SM tissue using microarray analysis. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) revealed 10 differentially expressed lncRNAs. Gene ontology and pathway analysis were performed to test the gene effect. Possible target genes of lncRNAs were predicted based on precise algorithms. RESULTS: Microarray analysis found many significantly differentially expressed lncRNAs and mRNAs in lung adenocarcinoma compared with SM. qRT-PCR results aligned with those of the microarray analysis. The expression level of 10 lncRNAs showed the same trend (P

To provide guidance for appropriate imaging examinations for diagnosing spinal tumors or tumor-like lesions.A total of 121 patients with suspected spinal tumors were included this retrospective study. Each patient underwent ≥2 imaging examinations, including computerized tomography (CT), magnetic resonance (MR), and/or emission computed tomography (ECT). All patients were diagnosed by pathology after core needle or surgical biopsies. The results were compared with those of pathological examinations using paired chi-squared tests, and compared with each other. Statistical indicators that tested the consistency of the results included McNemar's and kappa coefficients, as well as receiver operating characteristic curves.The differences among MR, CT, ECT, and pathology were not significant. The kappa coefficient of MR, CT, and ECT was 46.1%, 36.0%, and 55.9%, respectively. The area under the curve of ECT, MR, and CT scans was 0.809, 0.705, and 0.704, respectively; and the differences among them were significant (P .05). Post hoc multiple comparisons showed no significant differences among imaging examinations in terms of sensitivity, specificity, misdiagnosis rate, and coincidence rate (P .05). However, significant differences were noted in the kappa coefficient and missed diagnosis rate (P .05).Although ECT was the most accurate imaging method, its high cost and large radiation dosage limit its widespread application. Furthermore, MR verified spinal tumors more effectively; however, CT excluded them more efficiently. In summary, when all factors are considered, MR is still the optimal modality for the diagnosis of spinal tumors, especially during the initial screening.

Objective A retrospective study was designed to evaluate the effectiveness of CT-guided core needle biopsy in diagnosing spinal lesions through comparison with C-arm guidance. Methods From April 2013 to July 2017, a total of 188 patients, who suffered from spinal lesions or had malignant tumor history with a new spinal fracture, were included in this study. There were 96 men and 92 women, with an average of 57.1 years. A total of 238 core needle biopsies were performed. A total of 140 core needle biopsies were carried out under C-arm guidance in 102 patients (group 1); 98 core needle biopsies were carried out under CT guidance in 86 patients (group 2); 108 core needle biopsies were performed in thoracic vertebrae, 116 were in lumbar vertebrae, and 14 were in sacral vertebrae. Seventy-eight patients accepted surgical treatment after biopsies. For these patients, the histological pathologies of the biopsy and surgery were compared to evaluate the accuracy of the biopsy. For the other 110 patients who did not receive surgical treatment, the treatment response and the clinical course were used to evaluate the accuracy of the biopsy. The success rate, the diagnostic accuracy rate, the true positive/negative rate, and complications of the two groups were calculated and compared. Results There were no significant differences in sex, age, and lesion sites between the C-arm guidance group (group 1) and the CT guidance group (group 2). There were no complications in the two groups. Pathological diagnoses were established in 232 of 238 biopsies. They revealed that 52 were primary malignant tumors, 12 were benign tumors, 70 were metastatic tumors, 4 were tuberculosis, and 94 were classified as "other." The success rate of group 2 was higher than that of group 1, but it was not statistically significant (95.7% vs 100%; P = 0.098). According to the final diagnosis, the diagnostic accuracy rates were calculated and compared. There was no significant difference between the two groups (95.5% vs 96.9%; P = 0.835). The kappa coefficient was used to analyze the concordance between the histological pathologies of the biopsy and the final diagnosis in the two groups. The kappa values of the two group were 0.909 and 0.939, respectively. The results showed good consistency in both groups, but seemed better for group 2. Conclusion CT-guided core needle biopsy is a relatively safe and effective procedure for diagnosing spinal lesions with a high diagnostic accuracy rate and few complications.

Background Studies on professional identity and related factors among Chinese general practitioners (GPs) are unavailable. The objective of this study was to investigate the professional identity level of GPs in China and explore factors associated with GPs’ perceptions of their professional identity. Methods A multistage stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs working in community health service institutions (CHIs) in China between October, 2017 and February, 2018. Professional identity was measured by the 13 items scale. Descriptive statistics were calculated and groups’ differences were estimated using nonparametric tests. Multiple linear stepwise regression analysis was used to analyze factors associated with professional identity among GPs. Results Based on a total score of 65 on the professional identity scale, the average score for GPs’ professional identity was 51.23 (SD = 6.56). Multiple linear stepwise regression analysis showed that GPs who practiced in Central China, with an administrative responsibility, at a moderate or higher income level, who frequently worked overtime, had more occupational development opportunities, with a higher level of job satisfaction and older GPs had higher levels of professional identity. Conclusions Professional identity level among GPs in China is high. Region, administrative responsibility, income level, working overtime, occupational development opportunities, age, and job satisfaction were significant predictors of professional identity.

Multiple myeloma is genetically heterogeneous with varied clinical outcomes, primarily due to the coexistence of diverse numerical and structural cytogenetic abnormalities. The prognostic impact of hyperdiploidy in myeloma patients with high-risk cytogenetics remains controversial in Western studies and is unknown in China. We examined the cytogenetic features of hyperdiploidy in 201 Chinese patients with newly diagnosed myeloma using magnetic-activated cell sorting and interphase fluorescence in situ hybridization and analyzed the effect of hyperdiploidy on the prognosis of patients with high-risk cytogenetics. Hyperdiploidy was detected in 50.7% (102/201) of the examined patients, and the incidence of hyperdiploidy coexisting with high-risk cytogenetics [del(17p13), +1q21 and adverse t(14q32)] was 33.8% (68/201). Survival analysis showed that the median progression-free survival (PFS) and 2-year overall survival (OS) of patients were better for hyperdiploidy than those for non-hyperdiploidy (43 vs. 20 months, P = 0.01; 86.8% vs. 70.5%, P = 0.04) and for standard-risk cytogenetics than those for high-risk cytogenetics (not reached vs. 23 months, P = 0.0001; 87.6% vs. 74.4%, P = 0.01). Strikingly, the high-risk cytogenetics patients with hyperdiploidy showed a better median PFS than those without hyperdiploidy (34 vs. 15 months, P = 0.01); however, compared to standard-risk cytogenetics patients, the median PFS and 2-year OS were poorer (34 months vs. not reached, P = 0.02; 78.8% vs. 87.6%, P = 0.05). The independent predictors of PFS were non-hyperdiploidy, high-risk cytogenetics, and bone marrow plasma cells ≥ 30%, with hazard ratios of 2.01 (95% CI 1.25–3.25), 2.56 (95% CI 1.38–4.74), and 1.81 (95% CI 1.08–3.05), respectively, and those for OS were non-hyperdiploidy and serum lactate dehydrogenase ≥ 250 U/L, with hazard ratios of 2.53 (95% CI 1.24–5.46) and 3.53 (95% CI 1.50–6.96), respectively. These results suggest that the coexistence of hyperdiploidy may ameliorate the adverse prognosis of multiple myeloma patients with high-risk cytogenetics. High-risk cytogenetics patients without hyperdiploidy showed the worst prognosis.

Due to radical resection, total en-bloc spondylectomy (TES) is associated with significant levels of surgical injury and spinal instability, particularly in elderly patients with solitary spinal metastases (SM), whether the possible benefits outweigh the risk requires intense consideration. Our aim was to compare and analyze the impact of age on patient prognosis.This study investigated TES in 78 consecutive patients with solitary SM, who were divided into Group A (65 years, n = 32) and group B (60 years of age, n = 46). Surgical outcomes were assessed according to survival time, local recurrence, neurological function, pain, and quality of life before and after surgery. Differences between groups were statistically compared using analysis of variance (ANOVA) or chi-square tests.There was no significant difference between the two groups in terms of surgery duration, blood loss, blood transfusion or the duration of hospital stay (p 0.05). Furthermore, there was no significant difference in the median survival time between the two groups (p 0.05). However, the perioperative complication rate in group A was higher than that in group B (p 0.05). There was no significant difference in terms of local recurrence rate when compared between group A and group B (p 0.05), and there were no significant differences in terms of improvements in neurological function, Visual Analogue Scale and Karnofsky scores of patients between the two groups (p 0.05).Older patients can experience survival and local recurrence rates that were similar to those of younger patients. Although older patients are at increased risk of perioperative complications, this factor does not appear to lead to serious adverse outcomes. Older patients are still good candidates to receive TES to cure solitary SM after careful preparation and strict selection.

Lung cancer invading the spine was previously considered unresectable and fatal and, consequently, there are few reports focusing on tumors located in the lower lung lobe and invading the spine. With the development of spinal instrumentation and surgical techniques, and wider acceptance of spondylectomy by surgeons, radical surgical resection has become feasible. Here, we present a case of a male patient with a left lower lung cancer invading thoracic vertebrae who underwent complete resection with sagittal en bloc hemivertebrectomy with video-assisted thoracoscopy. A 60-year-old man complained of left chest pain for 3 months. Chest computed tomography and thoracic vertebrae magnetic resonance image revealed that a tumor in the left lower lung lobe had invaded the seventh and eighth thoracic vertebrae and the eighth rib. As no lymph node or distant metastasis was detected by positron emission tomography-computed tomography, the patient was diagnosed with left lower lung cancer directly invading the seventh and eighth thoracic vertebrae and the eighth rib (T4N0M0, stage IIIA) instead of metastasizing to the thoracic vertebrae. An en bloc resection of the lung tumor and the involved vertebrae was performed by a thoracic surgeon and orthopaedic surgeon with video-assisted thoracoscopy. Six months after the operation, there was no evidence of local recurrence, and the patient had recovered well. En Bloc resection with video-assisted thoracoscopy for lung cancer invading thoracic vertebrae is a safe and feasible surgical method. This method can significantly improve the safety and convenience of this type of surgery.

Background Growing evidence has supported that long non-coding RNAs (lncRNAs) could play vital roles in the development, progression, and prognosis of colorectal cancer (CRC). However, little is known about the clinical significance of BRAF-activated non-coding RNA (BANCR) in CRC. The aim of this study is to explore the clinical value of lncRNA BANCR in CRC patients. Methods The expression of lncRNA BANCR was measured in 106 CRC tissues and 65 adjacent normal tissues using the quantitative real-time PCR. Results The study showed that lncRNA BANCR was highly expressed in CRC tissues compared with adjacent normal tissues (P < 0.001). In addition, high expression of lncRNA BANCR was positively correlated with the lymph node metastasis (P < 0.001). Kaplan–Meier analysis showed that patients with high lncRNA BANCR expression had a shorter overall survival (OS) compared with the low lncRNA BANCR expression group (P = 0.001). Interestingly, for the group of patients with the lymph node metastasis, we found the similar result that high lncRNA BANCR expression was related to poor OS (P = 0.004). Furthermore, the multivariate Cox regression model analysis indicated that high expression of lncRNA BANCR was an independent poor prognostic factor in CRC patients (HR 2.24, 95% CI 1.22–4.16, P = 0.009). Conclusions Upregulation of lncRNA BANCR may be associated with the lymph node metastasis and poor survival of CRC. LncRNA BANCR could be served as a novel and useful biomarker for CRC lymph node metastasis and prognosis.

A retrospective clinical study.This study sought to retrospectively compare the mid-term to long-term outcomes between unilateral pedicle screw (UPS) and bilateral pedicle screw (BPS) augmented transforaminal lumbar interbody fusion (TLIF) in lumbar degenerative diseases.Recently, UPS fixation has been applied in TLIF, for its satisfactory clinical outcome, less implants and less invasiveness. However, only short-term outcome has been reported, the mid-term to long-term outcome has not been well characterized.From June 2007 to February 2011, 215 of 348 consecutive patients suffering from lumbar degenerative diseases were operated in our hospital and accomplished a minimum of 4-year follow-up. These patients were divided into 2 groups according to the operative techniques: UPS group (n=109), and bilateral pedicle screw group (n=106). Operative time, blood loss, length of hospital stay, hospital bill, fusion status, and complications were recorded and analyzed statistically. Visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores were used to assess the preoperative and postoperative pain and functional outcome.The mean follow-up duration was 52.2 months. A significant decrease occurred in operative time, blood loss, and hospital bill in unilateral group, compared with bilateral group (P0.05). The average postoperative visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores improved significantly in each group than the preoperative counterparts (P0.05); however, there were no significant difference between groups at any follow-up time point (P0.05). No statistically difference was detected regarding fusion rate and complication rate between the 2 groups (P0.05), except the cage migration rate (P0.05).UPS fixation could achieve satisfactory clinical outcome similar to bilateral fixation in TLIF at a mid-term to long-term follow-up. To avoid cage migration, bullet-shaped cages should not be used in the unilateral group.

The pathogenesis of Huntington's disease (HD), an inherited progressive neurodegenerative disease, is highly associated with the cytotoxicity-inducing mutant huntingtin (mHtt) protein. Emerging evidence indicates that autophagy plays a pivotal role in degrading aggregated proteins such as mHtt to enhance neuronal viability. In this study, by employing preparative high-performance liquid chromatography (pre-HPLC), ultra-high performance liquid chromatography diode-array-detector quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF-MS) and nuclear magnetic resonance (NMR), three escins, escin IA (EA), escin IB (EB) and isoescin IA (IEA), were isolated and identified from the seed of Aesculus chinensis Bge. (ACB). After EGFP-HTT74-overexpressing HT22 cells were treated with EA, EB and IEA at safe concentrations, the clearance of mHtt and mHtt-induced apoptosis were investigated by Western blot, immunofluorescence microscopy and flow cytometry methods. In addition, the autophagy induced by these escins in HT22 cells was monitored by detecting GFP-LC3 puncta, P62 and LC3 protein expression. The results showed that EA, EB and IEA could significantly decrease mHtt levels and inhibit its induced apoptosis in HT22 cells. In addition, these three saponins induced autophagic flux by increasing the ratio of RFP-LC3 to GFP-LC3, and by decreasing P62 expression. Among the tested escins, EB displayed the best autophagy induction, which was regulated via both the mTOR and ERK signaling pathways. Furthermore, the degradation of mHtt and the commensurate decrease in its cytotoxic effects by EA, EB and IEA were demonstrated to be closely associated with autophagy induction, which depended on ATG7. In conclusion, we are the first to report that the escins, including EA, EB and IEA are novel autophagy inducers that degrade mHtt and inhibit mHtt-induced apoptosis in vitro and in vivo. As a result of these findings, the triterpenoid saponins in ACB might be considered to be promising candidates for the treatment of HD in the future.

Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1–3 intravenously. After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients

Objectives: Investigation is scare on job satisfaction among general practitioners (GPs) in China. This study aimed to investigate job satisfaction of GPs in China and explore its determinants. Methods: A multistage-stratified random sampling method was used to collect data with a structured self-administered questionnaire from 3236 GPs (response rate, 99.8%) working in community health institutions in China between October 2017 and February 2018. Multiple linear stepwise regression analysis was used to analyze the associated factors with job satisfaction among GPs. Results: Among these respondents, 1215 (37.5%), 352 (10.9%), and 1669 (51.6%) GPs were dissatisfied, moderate, and satisfied for their current job, respectively. Male GPs, a higher education level, at a higher professional title, at a lower level of income, and those with heavy work stress had a lower job satisfaction. In addition, GPs who often worked overtime, who were at a higher level of emotional exhaustion, at a higher level of depersonalization, at a lower level of personal accomplishment, and who had less occupational development opportunities reported a lower level of job satisfaction. Conclusion: These findings suggest that job satisfaction among Chinese GPs is at a moderate level. Region, sex, professional title, education level, working overtime, income level, emotional exhaustion, depersonalization, personal accomplishment, work stress, and occupational development opportunities were significant predictors of job satisfaction.

Summary The relationship between insomnia and hypertension remains inconclusive. Thus, we conducted a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of hypertension. Relevant prospective cohort studies were searched from PubMed, Embase, and Web of Science from their inception to October 2019. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). A total of fourteen prospective cohort studies involving 395,641 participants were included in this study. The pooled RR of insomnia on hypertension was 1.21 (95%CI: 1.10–1.33). An increased risk of hypertension was observed in participants with difficulty maintaining sleep (RR = 1.27; 95%CI: 1.04–1.55) and early morning awakening (RR = 1.14; 95%CI: 1.08–1.20), but was not statistically significant in participants with difficulty falling asleep (RR = 1.14; 95%CI: 0.95–1.37). In addition, the results were statistically significant in the European population (RR = 1.08, 95%CI: 1.02–1.14), but not significant in Asian and American populations (RR = 1.54, 95%CI: 0.98–2.40; RR = 1.21, 95%CI: 0.89–1.65). The study findings indicate that insomnia is associated with a significantly increased risk of hypertension. This may have substantial implications for the prevention of hypertension in individuals with insomnia symptoms.

Intestinal barrier involves in the pathogeny of inflammatory bowel disease (IBD) and hydrogen sulfide (H2S) has been reported to improve intestinal barrier integrity. Thus, this study investigated the effects of GYY4137, a slow-release H2S donor, on DSS-induced inflammation and intestinal dysfunction. In vitro model, cellular permeability was significantly increased and expression of tight junctions (ZO-1, Cauldin4, and Occludin) was downregulated in Caco-2 cells. GYY4137 treatment markedly attenuated DSS-induced inflammation and barrier dysfunction. Cystathionine β-synthase (CBS)-siRNA transfection further demonstrated that endogenous H2S system involves in DSS-induced inflammation and mediates barrier function. In vivo model, DSS exposure caused colonic inflammation and injury in mice and GYY4137 injection alleviated inflammatory response and improved intestinal barrier via reducing intestinal permeability and upregulating of tight junctions. In conclusion, endogenous H2S system involves in DSS-induced inflammation and H2S addition alleviated inflammation and intestinal dysfunction in vitro and in vivo.

Spinal tumors result in high morbidity and a high rate of lower limb paralysis. Both surgical therapy and radiation therapy (RT) are used to treat spinal tumors; however, how best to combine these two therapies to maximize the benefits and minimize the risks is still being debated. It is also difficult to decide the optimal timing, course and dose of RT, especially in pregnant women and children. The aim of this review is to assist surgeons who are dealing with spinal tumors by providing comprehensive information about advanced techniques for administering RT with greater precision and safety, and about the impact of various ways of combining surgery and RT on therapeutic outcomes. We here review published reports about treating spinal tumors with a combination of these two forms of therapy and attempt to draw appropriate conclusions concerning selection of optimal treatment protocols. Our conclusion is that postoperative radiotherapy, especially with high-precision, low-dose and multiple fractions, and brachytherapy are promising therapies to combined with surgery.

The aim of our study was to evaluate the prognostic impact of minimal residual disease (MRD) and high-risk cytogenetics (HRCs) on outcomes in multiple myeloma (MM) patients. We applied multiparameter flow cytometry (MFC) to detect MRD in 123 consecutive patients diagnosed with MM for the first time who achieved very good partial remission (VGPR) or better after bortezomib or thalidomide-based induction therapy. Moreover, we examined the cytogenetic features of MM patients using magnetic-activated cell sorting and interphase fluorescence in situ hybridization (MACS-iFISH) at diagnosis. In all 123 MM patients, progression-free survival (PFS) and overall survival (OS) were better in the MRD− group (n = 31) than in the MRD+ group (n = 92) (median PFS: not reached (NR) vs. 26 months (m), P = 0.0002; 4-year OS, 91.7% vs. 66.3%, P = 0.008). PFS and OS were significantly shorter for each increase of one log per MRD level (P

The self-locking stand-alone cage has been clinically applied in treating cervical degenerative disc disease (CDDD). However, no long-term clinical and radiographic studies have been performed so far. This retrospective study was designed to analyze and compare the efficacy and outcomes of anterior cervical discectomy and fusion (ACDF) using self-locking stand-alone cages and cages with the anterior cervical plating system.A total of 98 consecutive patients were recruited in this study. Patients in the cage group were given stand-alone self-locking cages, and patients in the plate group were treated with cages and anterior plate fixation. The operative time, intraoperative blood loss and complications were recorded. Clinical outcomes were evaluated using the JOA scoring system, Neck Disability Index and Odom's criteria. The cervical lordosis, subsidence and cervical fusion status were assessed by X-ray and computed tomography.The mean follow-up period was 39.7 months in the cage group and 42.2 months in the plate group. The operative time, intraoperative blood loss, postoperative dysphagia, sore throat and adjacent segment degeneration in the cage group were significantly less than those in the plate group (p 0.05). All the patients in both groups achieved complete interbody fusion. Postoperative JOA and NDI scores in both groups were obviously improved compared with the preoperative ones. The postoperative cervical lordosis was effectively restored in both groups.The self-locking stand-alone cage for ACDF could effectively restore the cervical physiological curvature, cause few complications, and lead to satisfactory outcomes. Therefore, it could be used as an effective and reliable treatment for the CDDD.

Background Amyloid light-chain (AL) amyloidosis is a disease caused by tissue deposition of light-chain proteins in vital organs that results in progressive organ damage. We analyzed the clinical characteristics of 123 AL amyloidosis patients and performed an overall survival (OS) analysis to identify critical baseline factors. Patients and Methods Patients (median age, 54 years) were diagnosed with organ involvement of kidney (98.4%), gastrointestinal (73%), cardiac (56%), liver (13%), or nervous system (10%), and multiorgan involvement was observed in 91% of patients. Treatment regimens of transplantation, bortezomib plus dexamethasone, melphalan plus dexamethasone, and prednisone-based regimens or no treatment resulted in 3-year OS rates of 72%, 60%, 55%, and 41%, respectively. Results Median OS was 38 months and was affected by age (≥ 65 years), hypoalbuminemia, renal failure, heart involvement, and organ response time (within 3 months). Multivariate analysis indicated that these were independent prognostic factors on OS except for age. Conclusion The AL amyloidosis patients in this study presented somewhat different features and outcomes compared to others, with younger age and higher rates of organ involvement.

Plants that spontaneously produce lesion mimics or spots, without any signs of obvious adversity, such as pesticide and mechanical damage, or pathogen infection, are so-called lesion mimic mutants (lmms). In rice, many lmms exhibit enhanced resistance to pathogens, which provides a unique opportunity to uncover the molecular mechanism underlying lmms. We isolated a rice light-dependent leaf lesion mimic mutant 1 (llm1). Lesion spots appeared in the leaves of the llm1 mutant at the tillering stage. Furthermore, the mutant llm1 had similar agronomic traits to wild type rice. Trypan blue and diamiobenzidine staining analyses revealed that the lesion spot formation on the llm1 mutant was due to programmed cell death and reactive oxygen species. The chloroplasts were severely damaged in the llm1 mutant, suggesting that chloroplast damage was associated with the formation of lesion spots in llm1. More importantly, llm1 exhibited enhanced resistance to bacterial blight pathogens within increased expression of pathogenesis related genes (PRs). Using a map-based cloning approach, we delimited the LLM1 locus to a 121-kb interval between two simple sequence repeat markers, RM17470 and RM17473, on chromosome 4. We sequenced the candidate genes on the interval and found that a base mutation had substituted adenine phosphate for thymine in the last exon of LOC_Os04g52130, which led to an amino acid change (Asp(388) to Val) in the llm1 mutant. Our investigation showed that the putative coproporphyrinogen III oxidase (CPOX) encoded by LOC_Os04g52130 was produced by LLM1 and that amino acid Asp(388) was essential for CPOX function. Our study provides the basis for further investigations into the mechanism underlying lesion mimic initiation associated with LLM1.

Sleeve gastrectomy plus side-to-side jejunoileal anastomosis (JI-SG), a relatively new approach to bariatric surgeries, has shown promising results for treating obesity and metabolic comorbidities. This study investigated the feasibility and safety of JI-SG in weight loss and diabetes remission compared with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Forty 10-week-old male Zucker diabetic fatty rats were randomly assigned to four groups: control, SG, JI-SG, and RYGB. Their body weights, food intake, and levels of gut hormones (ghrelin, insulin, and glucagon-like peptide-1 (GLP-1)) and lipids were measured. Rats in the SG, JI-SG, and RYGB groups demonstrated lower food intake and more weight loss 2 weeks postoperatively compared with control rats. Furthermore, rats in the JI-SG group achieved more weight loss (mean 242.7 ± 11.2 g) compared with those in the SG and RYGB groups (SG, 401.4 ± 15.1 g and RYGB, 298 ± 12 g, both P

Extracellular acidification occurs under physiologic and pathologic conditions, such as exercise, ischemia, and inflammation. It has been shown that acidosis has various adverse effects on bone. In recent years there has been increasing evidence which indicates that ovarian cancer G protein-coupled receptor 1 (OGR1) is a pH-sensing receptor and mediates a variety of extracellular acidification-induced actions on bone cells and other cell types. Recent studies have shown that OGR1 is involved in the regulation of osteoclast differentiation, survival, and function, as well as osteoblast differentiation and bone formation. Moreover, OGR1 also regulates acid-induced apoptosis of endplate chondrocytes in intervertebral discs. These observations demonstrate the importance of OGR1 in skeletal development and metabolism. Here, we provide an overview of OGR1 regulation ofosteoclasts, osteoblasts, and chondrocytes, and the molecular actions of OGR1 induced by extracellular acidification in the maintenance of bone health.

Study design This was a prospective study on the clinical outcomes of single-stage surgery for thoracic and lumbar spine tuberculosis patients with bilateral paraspinal or bilateral psoas abscesses. Objective The aim of this study was to investigate the feasibility of, indications for, and clinical effects of single-stage posterior surgery for the treatment of thoracic and lumbar spinal tuberculosis with bilateral paraspinal or bilateral psoas abscesses. Summary of background data An increasing number of articles have been published on the use of single-stage surgery for spinal tuberculosis; however, none of these articles have discussed the use of such surgery in patients with bilateral abscesses. Methods Between January 2003 and January 2011, 41 patients with thoracic and lumbar spinal tuberculosis and bilateral paraspinal or bilateral psoas abscesses were treated with single-stage posterior surgery. All of the patients were treated preoperatively with 1-2 weeks of antituberculosis drugs. All patients were managed postoperatively with standard courses of chemotherapy with triple or quadruple antituberculosis drugs. The clinical symptoms, complications, and laboratory and image indicators were recorded. Results There were no local recurrences except in one L3-L4 tuberculosis patient. Two patients presented with extraspinal tuberculosis in the third year. There were no incision complications. Bone fusion was observed 6 months after the operation. The erythrocyte sedimentation rate was normal at 3 weeks-3 months postoperatively. There were no internal fixation failures. The internal fixations in 6 young patients were removed after the spinal tuberculosis was cured. Conclusions Single-stage posterior surgery with instrumentation results in less operative trauma and can be a suitable alternative for treating thoracic and lumbar tuberculosis with bilateral paraspinal or bilateral psoas abscesses.

It has been reported that anterior cervical decompression has good clinical outcomes for the treatment of adjacent three-level cervical spondylotic myelopathy (CSM). However, the application of a long plate in the anterior cervical spine poses substantial risks of soft tissue damage. In this retrospective study, we aimed to analyze the clinical and radiological results of the hybrid construction with titanium mesh cage (TMC) plus plate and self-locking stand-alone cage for treatment of adjacent three-level CSM. A total of 28 consecutive patients with adjacent three-level CSM were treated by anterior decompression and hybrid reconstruction with TMC plus plate and self-locking stand-alone cage. Clinical outcomes, complications, fusion rate and time, cage subsidence and spinal curvature were assessed. The mean follow-up period was 22.8months. The average operative time was 103±18.5min, and the average blood loss was 115±13.3mL. The JOA score and degree of spinal curvature were significantly increased at the final follow-up compared with preoperatively (P0.05). Twenty-seven cases finally achieved a solid fusion, and the average time to achieve a solid fusion was 6.2months. Postoperative complications included one case of cerebrospinal fluid leakage (3.57%), one case of temporary sore throat (3.57%) and two cases of TMC subsidence (7.1%). No dysphagia and hoarseness were observed. Anterior decompression and hybrid reconstruction with TMC plus plate and self-locking stand-alone cage could be used safely and effectively for the treatment of adjacent three-level CSM. It could effectively restore cervical lordosis, reduce the complications related to long plate fixation, and lead to satisfactory outcomes.

Background The purpose of this biomechanical in vitro study was to compare the kinematics and intradiscal pressure achieved with 2 methods: L4–L5 pedicle screw-rod fixation (PSRF) with an upper L3–L4 Coflex device and L4–L5 PSRF alone. The results were used to characterize the biomechanics of the topping-off operation with a Coflex device for the lumbar motion segment adjacent to single-level rigid fixation. Material/Methods Six human cadaveric spine specimens were biomechanically tested in vitro (6 males, 0 females). The 3-dimensional specimen motion in response to applied loads during flexibility tests was determined. Loads were applied along anatomic axes to induce flexion-extension, lateral bending, and axial rotation. All specimens were first studied with intact lumbar motion segments, then with L4–L5 PSRF alone, and finally with L4–L5 PSRF with an upper L3–L4 Coflex device. A non-paired comparison of the 3 configurations under 3 different conditions was made. Results PSRF, with or without a Coflex device, significantly increased the range of motion (ROM) in the upper adjacent motion segments in all directions of loading. The intradiscal pressure (IDP) changed slightly. A correlation analysis showed that the ROM and IDP are significantly positively correlated. The application of the upper motion segment of the Coflex device provided greater stability in all directions of motion than did PSRF alone, particularly for extension (p0.05). Conclusions These results suggest that L4–L5 PSRF with an L3–L4 Coflex device is more stable than L4–L5 PSRF alone. PSRF with an upper Coflex device is a promising alternative to PSRF alone. Based on these biomechanical tests, it might be considered a protective method to prevent adjacent segment degeneration (ASD), although some limitations with this in vitro study must be addressed in the future.

For three or more involved cervical levels, there is a debate over which approach yields the best outcomes for the treatment of multilevel cervical degenerative disease. Our objective is to compare the radiological and clinical outcomes of two treatments for multilevel cervical degenerative disease: anterior cervical discectomy and fusion (ACDF) versus plate-only open-door laminoplasty (laminoplasty). Patients were randomized on a 1:1 randomization schedule with 17 patients in the ACDF group and 17 patients in the laminoplasty group. Clinical outcomes were assessed by a visual analog scale (VAS), Japanese Orthopedic Association (JOA) scores, operative time, blood loss, rates of complications, drainage volume, discharge days after surgery, and complications. The cervical spine curvature index (CI) and range of motion (ROM) were assessed with radiographs. The mean VAS score, the mean JOA score, and the rate of complications did not differ significantly between groups. The laminoplasty group had greater blood loss, a longer operative time, more drainage volume, and a longer hospital stay than the ACDF group. There were no significant differences in the CI and ROM between the two groups at baseline and at each follow-up time point. ROM in both groups decreased significantly after surgery. Both ACDF and laminoplasty are effective and safe treatments for multilevel cervical degenerative disease. ACDF causes fewer traumas than laminoplasty.

Object The object of this study was to compare the mini-open anterior corpectomy procedure with posterior total en bloc spondylectomy (TES) in treating patients with solitary metastases of the thoracolumbar spine. Methods From 2004 to 2010, 41 patients with solitary metastases of the thoracolumbar spine were treated in our hospital using either a mini-open anterior corpectomy or posterior TES. Intraoperative and diagnostic data, including perioperative complications, were collected using retrospective chart review. The surgical outcomes were assessed according to survival status, neurological function, local recurrence, and pain before and after surgery. Results Seventeen patients underwent posterior TES and 24 underwent mini-open anterior corpectomy. Mean blood loss (TES, 1721 ± 293 ml; mini-open corpectomy, 1058 ± 263 ml; p < 0.05), and mean operative time (TES, 403 ± 55 minutes; mini-open corpectomy, 175 ± 38 minutes; p < 0.05) were recorded and calculated. Neurological improvement by at least 1 American Spinal Injury Association Impairment Scale grade was noted in 35 (97.2%) of the 36 cases with preoperative deficits. After the operation, 68.4% of nonambulatory patients became ambulatory again, including 84.6% after mini-open corpectomy and 33.3% after posterior TES (p > 0.05). The visual analog scale scores of the patients were significantly reduced after both procedures, with no difference between the procedures (p > 0.05). The local tumor recurrence rate of the TES group was significantly lower than that of the mini-open corpectomy group (p < 0.05), while the postoperative survival rates within 2 years after surgery were similar. The complication rate in the mini-open corpectomy group (29.2%) was higher than that in the TES group (11.8%), but this difference was not statistically significant (p = 0.185). There was no hardware failure and no loss of the sagittal Cobb angle in either group. Slight subsidence (< 3 mm) of the mesh cage was observed with a successful fusion in 3 (17.6%) of 17 patients in the TES group. No subsidence of polymethylmethacrylate block/autograft was recorded in the mini-open group. Conclusions Mini-open anterior corpectomy can be accomplished with less blood loss, fewer fixation instrumentations, and shorter surgical time than that required for TES, but patients who undergo a mini-open corpectomy might have a greater tendency to experience local recurrence. A mini-open anterior corpectomy has a relatively mild learning curve and involves fewer technical difficulties. With smaller incisions, mini-open anterior corpectomy is an option in treating solitary metastases of the thoracolumbar spine.

To investigate the safety and therapeutic effects of mono-segmental pedicle instrumentation (MSPI) in treating thoracolumbar burst fracture (AO classification: A3.1 and A3.2).A retrospective analysis was conducted on 60 cases with thoracolumbar burst fracture (AO classification: A3.1 and A3.2) between April 2005 and February 2010. Half of the 60 inpatients were treated with MSPI, and the other half was treated with short-segment pedicle instrumentation (SSPI). The mean operation time, blood loss, visual analog scale (VAS) and vertebral kyphotic angle before and after surgery were compared.In the MSPI group, the mean operation time was 90 ± 25 min, and the blood loss at operation was 180 ± 62 ml. The vertebral kyphotic angles were 17.3° ± 9.3° before surgery, 6.5° ± 6.5° one week after surgery, and 9.5° ± 6.4° for the latest follow-up. The VAS scores were 7.5 ± 1.4 before surgery, 2.5 ± 0.7 one week after surgery, and 1.4 ± 0.8 for the latest follow-up. In the SSPI group, the mean operation time was 101 ± 28 min, and the blood loss at operation was 203 ± 88 ml. The follow-up duration was 12-64 months. The vertebral kyphotic angles were 16.5° ± 9.1° before surgery, 7.1° ± 6.9° one week after surgery, and 7.5° ± 5.2° for the latest follow-up. The VAS scores were 6.7 ± 1.5 before surgery, 3.0 ± 0.4 one week after surgery, and 1.1 ± 0.6 for the latest follow-up. There were no statistically significant differences between these two groups in the operation time, blood loss at operation, VAS score and vertebral kyphotic angle before and after surgery (p 0.05). The post-surgical VAS scores and vertebral kyphotic angles were significantly decreased in both groups, compared to before surgery (p 0.05).It is safe and effective to treat thoracolumbar burst fractures (AO 3.1 and AO 3.2) with MSPI. The mean operation time, blood loss at operation, post-surgical VAS and vertebral kyphotic angle of the MSPI group are similar, compared to the SSPI group. Further research is needed to find out whether therapeutic effects of MSPI are better than those of conservative treatment in these cases.

Anterior cervical plating is regarded as standard practice after multilevel anterior cervical discectomy and fusion. However, plate implantation in the anterior cervical spine poses a substantial risk of hardware-related complications. We retrospectively analyzed the efficacy and outcomes of 15 consecutive patients treated with a 3-level anterior cervical fusion using self-locking stand-alone polyetheretherketone (PEEK) cages. Patients were evaluated preoperatively and postoperatively using the Japanese Orthopedic Association (JOA) scale scores and radiographs. Clinical results were assessed using Odom's criteria. The mean JOA score (± standard deviation) improved significantly from 7.3 ± 1.5 points to 14.1 ± 1.3 points (p0.05) at the final follow-up. The outcomes were excellent for four patients (26.7%), good for nine patients (60%) and fair for two patients (13.3%). None of the patients experienced a poor clinical outcome. Thirteen patients achieved a solid fusion, after an average time of 5.7 months. The radiographic fusion rate of this procedure was 93.3%. Of 45 cages inserted in total, only four (8.89%) cages, in three patients, were found to have subsided. The degree of spinal curvature before surgery differed significantly from that immediately after surgery, and from that at the final follow-up examination (p0.05). Self-locking stand-alone PEEK cages packed with excised local osteophytes and calcium sulfate are safe and effective. This procedure can effectively restore cervical lordosis, obviate the complications related to graft harvest and screw-plate fixation, and lead to satisfactory outcomes.

Previous studies have shown that GSK-3β inhibitor could reduce infarct volume after ischemia brain injury. However, the underlying mechanisms of GSK-3β inhibitor involving neuroprotection remain poorly understood. In the present study, we demonstrated that GSK-3β inhibitor suppressed insult-induced neuroinflammation in rat cortex by increasing autophagy activation in ischemic injury. Male rats were subjected to pMCAO (permanent middle cerebral artery occlusion) followed by treating with SB216763, a GSK-3β inhibitor. We found that insult-induced inflammatory response was significantly decreased by intraperitoneal infusion of SB216763 in rat cortex. A higher level of autophagy was also detected after SB216763 treatment. In the cultured primary microglia, SB216763 activated autophagy and suppressed inflammatory response. Importantly, inhibition of autophagy by Beclin1-siRNA increased inflammatory response in the SB216763-treated microglia. These data suggest that GSK-3β inhibitor suppressed neuroinflammation by activating autophagy after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

There are several practical problems encountered in the TLIF procedure with implantation of two titanium cages, such as difficulty in achieving symmetric positioning with two cages, loosening of the first cage following insertion of the second cage and higher direct costs to the patient. From January 2005 to December 2007, a total of 76 consecutive patients treated with instrumented TLIF with single cage and excised local bone were enrolled in the current study. There were 45 males and 31 females aged between 31 and 75 years (mean 50.9 years). Forty-five patients had degenerative disc diseases alone, 23 had associated isthmic or degenerative spondylolisthesis and 8 had recurrent disc herniations. Clinical outcomes were evaluated using the Oswestry Disability Index and a visual analog scale. Intervertebral height and fusion status were assessed on X-ray and two-dimensional computed tomography reconstruction. All the patients followed up. The mean follow-up period was 21.8 months (range from 12 to 48 months). No nerve injuries occurred during operation. Postoperative ODI and VAS scores in all the patients were more than the preoperative ones with significant differences. All the patients had complete interbody fusion and, at the final follow-up, none had instrumentation failure. Postoperative intervertebral height in all the patients was better than the preoperative ones with statistical significances. Instrumented TLIF with single cage is a safe and effective method for the treatment of degenerative lumbar diseases.

Anterior cervical decompression and fusion (ACDF) is a widely accepted surgical procedure for the treatment of cervical degenerative disc diseases. This retrospective study was designed to analyze and compare the efficacy and outcomes of anterior cervical fusion using stand-alone polyetheretherketone (PEEK) cages and autogenous iliac crest grafts with the anterior cervical plating system. A total of 72 consecutive patients suffering from cervical degenerative disc diseases treated with ACDF from June 2005 to Dec 2008 were enrolled in the study. Patients in group A (40 patients, 64 segments) had anterior interbody fusion with stand-alone PEEK cages and patients in group B (32 patients, 51 segments) with autogenous iliac crest graft combined with anterior plate fixation. The operative time and intraoperative blood loss were recorded. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scoring system; cervical lordosis, intervertebral height, and cervical fusion status were assessed on X-ray and computed tomography. The mean follow-up period was 17.3 months in the stand-alone cage group and 23.2 months in the autologous iliac crest graft group. The operative time and intraoperative blood loss in group A were much less than those in group B (p

This study sought to retrospectively compare three different posterior fixation techniques in transforaminal lumbar interbody fusion for two-level lumbar degenerative diseases.This was a retrospective single-center study including 84 patients who underwent TLIF instrumented with unilateral pedicle screws (UPS), unilateral pedicle screws plus contra-lateral translaminar facet screws (UPSFS), or bilateral pedicle screws (BPS) between June 2008 and May 2012. These patients were divided into three groups: UPS (n=22), UPSFS (n=28) and BPS (n=34) group. Operative time, blood loss, length of hospital stay, hospital bill, fusion status and complications were recorded and analyzed statistically. Visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Scores (JOA) were used to assess the preoperative and postoperative pain and functional outcome. Sagittal alignment was evaluated by the segment lordosis (SL) and whole lumbar spine lordosis (LL).The mean follow up duration was 46.2 (ranging from 36 to 60) months. A significant decrease occurred in operative time, blood loss and hospital bill in UPS and UPSFS group, compared with BPS group (p0.05). The average postoperative VAS, ODI and JOA scores improved significantly in each group than the preoperative counterparts (p0.05), however, there were no significant difference between groups at any follow-up time point (p0.05). No statistically difference was detected regarding fusion rate and complication rate between groups (p0.05), except the screw/rod failure rate (p0.05). Radiographic analysis showed that the LLs in all these groups got improved (p0.05) and the SLs maintained (p0.05).UPS or UPSFS instrumented TLIF could achieve satisfactory mid-term clinical outcome comparable to BPS's, with less surgical time, less blood loss, and lower cost; UPS should be prudently performed for two-level cases in case of lower fusion rate, and cannulated screws should be replaced by stronger solid screws in UPSFS to reduce facet screw breakage.

Adamantinoma is a low-grade primary malignant bone tumour with slow growth and local recurrence. Its occurrence in the spine is extremely rare, particularly with multilevel involvement. This paper wants to present the first case involving a patient with recurrent thoracolumbar spinal adamantinoma, who underwent a successful three-level spondylectomy for en bloc resection. A 24-year-old man with osteolytic masses of T11 and T12 vertebral bodies was performed curettage by a posterior approach in 2008. The pathology report showed the excised neoplasm was a rare adamantinoma. This patient underwent a tumorectomy again because of its local recurrence nearly 3 years later. In 2012, it was unfortunately revealed that the excised tumour had relapsed and had spread to the L1 vertebral body. Due to its repeated recurrence and aggressive lesion, total en bloc spondylectomy (TES) for this malignant tumour was thought to be the best option for preventing repeated recurrence and possible cure. TES for T11–L1 thoracolumbar spine was performed and spinal reconstruction was completed with instrumentation and a titanium mesh cage through a one-stage single posterior approach. After three-level TES, neurological deficits of the patient demonstrated good recovery and no evidence of adamantinoma recurrence or deformity was found at 2-year follow-up. This is the first case involving multilevel thoracolumbar spinal adamantinoma with repeated recurrence to be successfully treated by three-level TES by a single posterior approach.

Previous studies have shown that multivesicular bodies (MVBs)/endosomes-mediated vesicular trafficking may play key roles in plant immunity and cell death. However, the molecular regulation is poorly understood in rice. Here we report the identification and characterization of a MVBs-localized AAA ATPase LRD6-6 in rice. Disruption of LRD6-6 leads to enhanced immunity and cell death in rice. The ATPase activity and homo-dimerization of LRD6-6 is essential for its regulation on plant immunity and cell death. An ATPase inactive mutation (LRD6-6E315Q) leads to dominant-negative inhibition in plants. The LRD6-6 protein co-localizes with the MVBs marker protein RabF1/ARA6 and interacts with ESCRT-III components OsSNF7 and OsVPS2. Further analysis reveals that LRD6-6 is required for MVBs-mediated vesicular trafficking and inhibits the biosynthesis of antimicrobial compounds. Collectively, our study shows that the AAA ATPase LRD6-6 inhibits plant immunity and cell death most likely through modulating MVBs-mediated vesicular trafficking in rice., Author Summary Plants have evolved sophistical immunity system in fighting against pathogenic micro-organisms including bacteria, fungi and oomycetes. Upon perception of pathogens, the immune system activates rapid cell death, characterized as a form of hypersensitive response typically in and around the infection sites to restrict pathogen invasion and prevent disease development. Recent studies have suggested that MVBs-mediated vesicular trafficking might play key roles in plant immunity and cell death. However, the molecular regulation is poorly known. By using the lesion resembling disease (lrd) mutant, lrd6-6, which exhibits autoimmunity and spontaneous cell death, we characterized LRD6-6 as a MVBs-localized AAA ATPase. We found that the ATPase LRD6-6 was required for MVBs-mediated vesicular trafficking and inhibited the biosynthesis of antimicrobial compounds for immune response in rice. Both the ATPase activity and homo-dimerization of LRD6-6 were essential for its inhibition on immunity and cell death. The catalytically inactive ATPase, LRD6-6E315Q, played dominant-negative effect on inhibition of immunity in plants. In addition, the LRD6-6 protein co-localized with the MVBs-spread marker protein RabF1/ARA6 and also interacted with ESCRT-III components OsSNF7 and OsVPS2. In summary, our study has shown that the AAA ATPase LRD6-6 inhibits plant immunity and cell death most likely through modulating MVBs-mediated vesicular trafficking in rice.

Background Zoledronic acid (ZOL) has been shown to significantly increase bone mineral density and to decrease the incidence of osteoporotic fractures. However, its safety when used after lumbar interbody fusion surgery remains unclear. We sought to determine whether ZOL infusion 3 days after transforaminal lumbar interbody fusion (TLIF) affects the risk of nonunion. Methods This was a randomized, double-blind, placebocontrolled trial involving subjects who underwent TLIF surgery. Eighty-two subjects (≥50 years of age) were randomly assigned to receive either 5 mg intravenous ZOL (N0 41) or placebo (N041) 3 days after surgery. Each patient received a lumbar computed tomography scan 6 months and 12 months postoperatively. We evaluated interbody fusion using the multiplanar reconstruction technique. Clinical outcomewas evaluated withthe Oswestry Disability Index.Bone turnover markers (amino terminal propeptides of type I collagen and C-telopeptide of type I collagen) were measured to investigate the biological effects of ZOL on spinal fusion. Results In the ZOL group, 7 levels (11.5%) exhibited nonunion; in the placebo group, 9 levels (14.5%) exhibited nonunion at 12 months postoperatively. This difference was not statistically significant (P00.82). The difference in ODI scores between two groups was not statistically significant at any of the follow-up times. However, ZOL decreased bone turnover markers significantly. Conclusions There was no association between ZOL treatment and nonunion of the lumbar spinal bone. Thus, undergoing lumbar interbody fusion surgery is not a valid reason to suspend or avoid treatment with ZOL.

Adequate fixation of the opened laminar arch is the key indicator of a successful laminoplasty surgery; poor outcomes, including secondary narrowing of the spinal canal and a high risk of axial neck pain are possible when using a suturing method during conventional laminoplasty. Rigid fixation including spacers or bone struts yields satisfactory clinical outcomes. However, this approach is also associated with a longer surgical time and an increased risk of instrumentation dislodgement. Plate-only fixation with fusion was developed in our hospital to improve conventional laminoplasty; in addition, the supraspinous ligament is preserved in this procedure. We evaluated both the safety and efficacy of the procedure. Twenty-six patients with multilevel cervical degenerative disease were enrolled for selective open-door laminoplasty with miniplate fixation; autologous bone debris was placed on the hinge side to promote fusion, without bone struts on the open side. The Japanese Orthopedic Association (JOA) score, X-ray, three-dimensional CT scan and MRI were used for the pre- and postoperative evaluations. The mean follow-up period was 22 months (range=12-34 months), and all patients achieved osseous fusion within six months of the operation. Patients who underwent open-door laminoplasty showed an improvement in the JOA score of 60.7%; a 23.0% incidence of axial neck pain and a 3.2° loss of range of motion (ROM) were also observed. No instrumentation failure or clinical deterioration was observed in our study. Thus, open-door laminoplasty with miniplate fixation is a safe, simple surgery for multilevel cervical disease that has significant clinical efficacy. This approach can maintain the cervical ROM, reduce the incidence of postoperative axial neck pain, decrease surgical time and cost, and avoid complications related to fusion.