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Objective To investigate the clinical effect of mouse nerve growth factor (mNGF) and methylcobalamin (MeCbl) for the treatment of lumbar disk herniation (LDH) with foot drop. Methods A total of 46 patients suffering from LDH with foot drop who underwent transforaminal lumbar interbody fusion (TLIF) surgery in our department from January 2015 to December 2017 were retrospectively analyzed. We divided these patients into two groups according to the different postoperative treatment which independently selected by patients after signing informed consent form: one group of 25 patients was treated with MeCbl alone (Group MeCbl), the other group of 21 patients was treated with a combination of mNGF and MeCbl (Group MeCbl+mNGF). Patient demographics, the visual analogue scale (VAS) scores, sensory and muscular strength improvement statistics at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively were recorded. Motor/sensory deficits, sciatica and overall neurological outcome after treatment of MeCbl alone and combination of mNGF and MeCbl were retrospectively analyzed. Results The follow‐up ranged between 12 and 42 months (mean 20.8 months). There were no significant differences between these two groups of patients with respect to sex ratio, age, smoking, diabetes, disease course, section of protruding disc(s), muscular strength of foot dorsiflexion or preoperative visual analogue scale (VAS) score (P > 0.05). The VAS scores of Group MeCbl+mNGF were significantly lower than Group MeCbl at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively (4.32 ± 0.75 vs 5.25 ± 0.79,2.65 ± 0.48 vs 3.42 ± 0.52, 1.72 ± 0.36 vs 2.45 ± 0.39, 1.12 ± 0.22 vs 1.52 ± 0.24, P < 0.05). The effective rates of sensory improvement were significantly higher in Group MeCbl+mNGF compared with Group MeCbl at 12‐week/12‐month follow‐up time point (90.48% vs 52.00%,95.24% vs 68.00%, P

Critical‐sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape‐adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe3O4 nanoparticles, as metal‐phenolic networks (MPN), is developed to easily prepare a fast gelling, shape‐adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe3O4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe3O4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical‐sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe3O4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal‐regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical‐sized bone defects. [ABSTRACT FROM AUTHOR]

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert‐butyl hydroperoxide‐induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2‐related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment. [ABSTRACT FROM AUTHOR]

To provide a basis for promising exosome‐based therapies against intervertebral disc degeneration (IDD), our present research aimed to identify a mechanism underlying the vesicle release from nucleus pulposus cells (NPCs). Scutellarin (SC) is a natural chemotherapeutic agent isolated from Erigeron breviscapus with a variety of biological activities. Here, we observed the significantly elevated autophagy levels in rat NPCs under the stimulation of SC, leading to a concomitant enhancement of intracellular vesicle release, which could be attributed to the inactivation of the phosphoinositide 3‐kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (Akt) pathway. To ensure that exosome release was driven by SC via the autophagic pathway, we implemented gain‐of‐function and loss‐of‐function studies by additionally using insulin‐like growth factor‐1 (IGF‐1) and small‐interfering RNA of autophagy‐related gene 5 (ATG5), and the exosome secretion decreased in the case of attenuated autophagy. Evidently, the treatment with SC exerted the remarkable upregulation of Rab8a through the overexpression of ATG5. After the respective knockdown of ATG5 and Rab8a, the increased release of exosomes induced by SC was reversed, whereas the number of intracellular vesicles was restored. Overall, it can be concluded that SC contributes to the autophagy activation in NPCs by acting on the PI3K/PTEN/Akt pathway, which upregulates the expression of Rab8a and promotes the release of exosomes, inspiring novel therapeutic strategies in preventing IDD that might be fruitfully investigated. [ABSTRACT FROM AUTHOR]

Although autophagy may be beneficial for maintaining the metabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) and its vitality under inflammation, the underlying mechanism still remains unclear. A previous study found that autophagy activation stimulated the release of exosomes in normal chondrocytes, which are located in a similar avascular environment and share many common features with those of nucleus pulposus cells (NPCs). This study explored the protective effect on matrix degradation in the NP by exosomes derived from autophagy‐activated NPCs and exosomal microRNAs. NPCs‐derived exosomes (NPCs‐Exos) were isolated from culture medium of either normal NPCs or rapamycin‐treated NPCs and quantified by nanoparticle tracking analysis. The effect of rapamycin‐treated NPC‐derived exosomes on NPCs were assessed by coculture with interleukin 1β (IL‐1β)‐stimulated NPCs. After examination of six major proteinases of the ECM, matrix metalloproteinase 13 (MMP‐13) was chosen for further study. miR‐27a, which targets MMP‐13, was investigated through previous studies and bioinformatics tool. The levels of miR‐27a were upregulated in both rapamycin‐treated NPCs and their exosomes, compared to the control. When exosomal miR‐27a was transferred into NPCs, it alleviated IL‐1β‐induced degradation of the NPC ECM by targeting MMP‐13. Autophagy activation may promote the release of NPCs‐derived exosomes and thereby prevent the NPC matrix from degradation. Autophagy activation also alleviates intervertebral disc degeneration (IDD), at least partly via exosomal miR‐27a, which restrains MMP‐13 expression under IL‐1β stimulation. Our work elucidates a new mechanism for how autophagy may participate in preventing IDD, which may be a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Decorin (Dcn) is a member of the class I small leucine‐rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)‐1β application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase‐3 and ‐13 and decreased the IL‐1β‐induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy‐related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL‐1β‐induced apoptosis and degeneration by promoting autophagy through mTOR signaling. [ABSTRACT FROM AUTHOR]

HCC stem cells were reported as posttreatment residual tumor cells that play a pivotal role in tumor relapse. Fusing dendritic cells (DCs) with tumor cells represents an ideal approach to effectively activate the antitumor immunity in vivo. DC/HCC stem cell vaccine provides a potential strategy to generate polyclonal immune response to multiple tumor stem cell antigens including those yet to be unidentified. To assess the potential capacity of DC/HCC stem cell vaccines against HCC, CD90+HepG2 cells were sorted from the HCC cell line HepG2. DC and CD90+HepG2 and DC and HepG2 fused cells were induced by polyethylene glycol (PEG). The influence of fusion cells on proliferation and immunological function transformation of lymphocytes was assessed by FCM and ELISA assay, respectively. The cytotoxicity assay of specific fusion cell-induced CTLs against HepG2 was conducted by CytoTox 96 Non-Radioactive Cytotoxicity Assay kit in vitro. At last, the prevention of HCC formation in vivo was described in a mouse model. The results of FCM analysis showed that the proportion of CD90+HepG2 cells in the spheral CD90+HepG2 enriched by suspension sphere culture was ranging from 98.7% to 99.5%, and 57.1% CD90+HepG2/DC fused cells were successfully constructed. The fusion cells expressed a higher level of costimulatory molecules CD80, CD83, CD86, and MHC-I and MHC-II molecules HLA-ABC and HLA-DR than did immature DCs (P<0.05). And the functional analysis of fusion cell-induced CTLs also illustrated that CD90+HepG2/DC fusion cells showed a greater capacity to activate proliferation of lymphocytes in vitro (P<0.05). The CD90+HepG2/DC-activated CTLs had a specific killing ability against CD90+HepG2 cells in vivo. These results suggested that CD90+HepG2/DC fusion cells could efficiently stimulate T lymphocytes to generate specific CTLs targeting CD90+HepG2 cells. It might be a promising strategy of immunotherapy for HCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a receptor for protons. We investigated the role of proton-sensing G protein-coupled receptors in the apoptosis of endplate chondrocytes induced by extracellular acid. The expression of proton-sensing G protein-coupled receptors was examined in rat lumbar endplate chondrocytes. Knockdown of OGR1 was achieved by transfecting chondrocytes with specific short hairpin RNA (shRNA) for OGR1. Apoptotic changes were evaluated by DNA fragmentation ELISA, electron microscopy, and flow cytometry. Intracellular calcium ([Ca2+]i) was analyzed with laser scanning confocal microscopy. The mechanism of OGR1 in acid-induced apoptosis of endplate chondrocytes was also investigated. We found that OGR1 was predominantly expressed in rat endplate chondrocytes, and its expression was highly upregulated in response to acidosis. Knocking down OGR1 with shRNAs effectively attenuated acid-induced apoptosis of endplate chondrocytes and increased [Ca2+]i. Blocking OGR1-mediated [Ca2+]i elevation inhibited acid-induced calcium-sensitive proteases such as calpain and calcineurin, and also inhibited the activation of Bid, Bad, and Caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). OGR1-mediated [Ca2+]i elevation has a crucial role in apoptosis of endplate chondrocytes by regulating activation of calcium-sensitive proteases and their downstream signaling. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective To study the therapeutic efficacy of the 'sandwich' method (medical glue + gelatin sponge + medical glue) of spinal dural repair for preventing cerebrospinal fluid ( CSF) leaks during treatment of subdural tumors. Methods Fifty-four patients with spinal subdural tumors treated between April 2007 and June 2011 were retrospectively investigated. The patients were divided into two groups: a conventional group ( Group A) and a 'sandwich' group ( Group B). The Group A patients included 16 males and 7 females with an average tumor course of 11 months (range, 2-34 months). Four of their 23 tumors were in the cervical spine, eight thoracic, and eleven lumbar. The Group B patients included 19 males and 12 females with an average tumor course of 12 months (range, 3-36 months). Five of their 31 tumors were in the cervical spines, 10 thoracic, and 16 lumbar. In Group A, the dural repairs were performed with interlocking sutures and a gelatin sponge covering the dura; whereas in Group B, they were performed with interlocking sutures, painting of medical glue around the dural incision, covering this with a gelatin sponge, and finally covering of the gelatin sponge with medical glue. The total volume of drainage after operation, incidence of CSF leaks, healing of the incision, and recovery of clinical performance were recorded. Results Compared to Group A patients, Group B patients had a significantly smaller total volume of drainage ( P < 0.05) on the day of surgery, and the first, second, and third postoperative days. The incidence of CSF leakage in Group B was also significantly less than in Group A ( P < 0.05). Before discharge, three patients in Group A developd hydrops, which was successfully treated by aspiration, continuous pressure from sandbags, and the prone position. During the first 3 months of follow-up, five patients developed deep hydrops under their incisions but required no treatment. There were no obvious abnormalities in Group B. Conclusion After removal of subdural spinal tumors by incising the dura mater, or in related spinal surgery, application of the 'sandwich' complex to the damaged spinal dura reduces the volume of drainage postoperatively and reduces the incidence of CSF leakage. [ABSTRACT FROM AUTHOR]

Abstract: 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 22months (range=12–34months), 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. [Copyright &y& Elsevier]

Sinibotia pulchra(Cypriniformes: Cobitidae) is a small cyprinid fish. In this study, the complete mitochondrial genome sequence ofS. pulchrais sequenced. TheS. pulchracomplete mitochondrial genome (GenBank accession no. KT362179) was a circular molecule of 16 568 bp in length, with 13 protein-coding genes (PCGs), 2 ribosome RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, an L-strand replication origin (OL) and a control region (D-loop). The nucleotide acid composition of the entire mitogenome was 31.69% for A, 25.63% for T, 26.94% for C and 15.74% for G, with an AT content of 57.32%. The AT content of 12S rRNA, 16S rRNA and D-loop was 50.21%, 56.86% and 66.74%, respectively. [ABSTRACT FROM AUTHOR]

Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes that were released into the extracellular space. In addition, in order to confirm that Rap-promoted release of exosomes was mediated by autophagy rather than other pathways, we used autophagy associated gene 5 (ATG5) small-interfering RNA (siRNA) to silence the expression of ATG5 gene, which is indispensable for autophagy. The results showed that siRNA against ATG5 (siATG5) induced an accumulation of intraluminal vesicles (ILVs) in NPCs and a concomitant decrease in the amount of exosomes isolated from supernatant. Ras homolog gene (Rho) and Rho-associated coiled-coil forming protein kinase (ROCK) family molecules are capable of cytoskeletal remodeling and affecting vesicle transport. Therefore, we carried out targeted interventions and evaluated the effects of the RhoC/ROCK2 pathway on the secretion of exosomes within autophagic environment. Knockdown of RhoC and ROCK2 with corresponding siRNA significantly inhibited the secretion of exosomes originating from ILVs in NPCs, even when NPCs were subsequently treated with Rap. Taken together, our findings suggest that autophagy positively regulates expression levels of RhoC and ROCK2, and that the RhoC/ROCK2 pathway exerts a key function on NPCs-derived exosome secretion. • The secretion of exosomes is positively correlated with autophagic levels of nucleus pulposus cells. • The activation of autophagy can upregulate the expression levels of RhoC and ROCK2. • The RhoC/ROCK2 pathway is a decisive factor for autophagy to promote exosome secretion of nucleus pulposus cells. [ABSTRACT FROM AUTHOR]