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Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING–NF–κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system (siSTING@HPgel) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery., Graphical abstract Image 1, Highlights • STING-NF-κB pathway activation was identified an important cause of intervertebral disc degeneration. • PAMAM was employed as both linker and gene vector for siRNA delivery. • The injectable self-healing hydrogel could significantly ease the IVD inflammation and degeneration by prolonging STING knockdown. • This novel hydrogel system opened new ways of thinking and had great potential for gene delivery.

Prospective cohort study.To assess the differences in the clinical and radiological outcomes between oblique lateral interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF).Nowadays, there is still a controversy regarding whether OLIF is superior to MI-TLIF in the management of degenerative lumbar disease.Between August 3, 2019 and February 3, 2020, 137 patients were assigned to OLIF or MI-TLIF at their request and the surgeon's discretion: 71 in the OLIF group and 66 in the MI-TLIF group. The perioperative data, patient-reported outcomes, radiographic outcomes, and complications were compared between the two groups.The OLIF group showed shorter operation time (110.5 vs.183.8 minutes, P 0.001), lesser estimated blood loss (123.1 vs. 232.0 mL, P 0.001), shorter length of hospital stay (5.5 vs. 6.7 days, P 0.001), and lower serum creatine kinase (CK) (1 day postoperatively) (376.0 vs. 541.8 IU/L, P 0.01) than that of MI-TLIF group. Both groups showed no significant differences in the visual analog scale (VAS) scores of lower back and leg pain and the Oswestry Disability Index (ODI) scores preoperatively and at 1, 3, and 12 months postoperatively, respectively (P 0.05). Compared with the MI-TLIF group, the OLIF group showed better restoration of disc height (DH) (4.7/4.6/4.7 vs. 3.7/3.7/3.7 mm, P 0.01) and lumbar lordosis angle (LLA) (10.5°/10.8°/11.1° vs. 5.8°/5.7°/5.3°, P 0.001), but not the value of segmental lordosis angle (SLA) (P 0.05) at 1 day, 1 month, and 1 year postoperatively, respectively. The complication rate of OLIF was higher than that of MI-TLIF (29.4% vs. 9.7%, P 0.01).Compared with MI-TLIF, OLIF showed similar results in terms of patient-reported outcomes, restoration of SLA and fusion rate, and superior results with respect to restoration of DH and LLA, operation time, estimated blood loss, length of hospital stay, and serum CK levels (1 day postoperatively). Even though the complication rate of OLIF is higher than that of MI-TLIF, it does not bring persistent and substantial damage to the patients.Level of Evidence: 3.

Objective The aim of the present paper was to evaluate cases of lumbar degenerative diseases treated with oblique lateral interbody fusion (OLIF) using a modified lateral approach (i.e. anteroinferior psoas exposure under direct vision) and to analyze the effect and safety of this approach. Methods From June 2016 to April 2019, a total of 226 patients with an average age of 65.5 ± 16.2 years (98 men and 128 women) with degenerative lumbar diseases who underwent the AIP approach of OLIF were followed up and analyzed retrospectively. Data concerning operative and clinical parameters were collected, including operative time, intraoperative estimated blood loss, duration of postoperative hospital stay, and time to ambulation after surgery. For the assessment of clinical outcomes, the visual analogue scale (VAS) score (for back pain) and the Oswestry disability index (ODI) were calculated. Complications were also recorded as surgical exposure approach‐related complications. More than 6 months after surgery, 132 patients consented to having MRI examinations to evaluate the psoas muscle atrophy when they were followed up. Results The mean operative time was 82.5 ± 31.6 min. The mean operative time for each segment of OLIF was 43.3 ± 15.5 min. The mean blood loss was 48.0 ± 11.6 mL. The mean blood loss for each segment of OLIF was 25.3 ± 10.1 mL. No patients needed blood transfusion intraoperatively or postoperatively. The mean hospital stay was 4.1 ± 2.1 days. All patients were followed up for 12–31 months (mean 18.2 months). Clinical assessment showed that the VAS and ODI scores at 6 months after surgery were markedly lower than the preoperative scores (P 0.05). There was no significant difference in percentage changes of the cross‐sectional area of the lean psoas muscle and the T2 signal intensity ratio of gross psoas to quadratus lumborum muscles between the left side (operative side) and the right side (nonoperative side) (P > 0.05). A total of 11 surgical exposure approach‐related complications were reported, with an incidence of 4.9%: transient thigh pain/numbness, psoas weakness (2.2%), sympathetic chain injury (1.3%), cage subsidence (0.9%), and segmental artery injury (0.4%). There was no permanent motor neurological deficit, and no injury of vascular, ureter or peritoneal membranes. Conclusion The anteroinferior psoas approach for OLIF is safe and can preserve the psoas and lumbar plexus., We presented a modified lateral approach (i.e. anteroinferior psoas exposure under direct vision) for OLIF and found that it is safe and can preserve the psoas and the lumbar plexus.

Background A postoperative discal pseudocyst (PDP) is a cystic lesion that is formed in the operation area of the intervertebral disc, leading to recurrence or even worse symptoms. To our knowledge, to date, there is no research focusing specifically on PDP following percutaneous endoscopic interlaminar discectomy (PEID). Case presentation We present the case of a 27‐year‐old man with L5S1 intervertebral disc herniation who was treated with PEID after failed conservative treatment. His leg pain was relieved immediately but reoccurred on the 40th day. MRI showed a PDP. Because loxoprofen and bedrest were ineffective and the patient was anxious, we performed a cystectomy. The patient's symptoms were significantly relieved, and a 6‐month follow up showed no recurrence both clinically and on MRI. Conclusion A PDP is more likely to form using the interlaminar approach than the transforaminal approach. For patients with mental stress, severe pain, and neurological symptoms, surgery is suggested to remove the cyst. Discectomy cannot be performed when disc degeneration is mild., We present the case of a 27‐year‐old man with L5S1 intervertebral disc herniation who was treated with PEID after failed conservative treatment. His leg pain was relieved immediately but reoccurred on the 40th day. MRI showed a PDP. Because loxoprofen and bed rest were ineffective and the patient was anxious, we performed a cystectomy. The patient's symptoms were significantly relieved, and a 6‐month follow‐up showed no recurrence both clinically and on MRI.

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to i...

Osteoporosis is caused by an imbalance between bone formation and bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) promotes the activity and differentiation of osteoclasts via activating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. IMD 0354 is a selective molecular inhibitor of inhibitor of NF-κB kinase subunit beta (IKKβ) and effective for treatment of acute and subacute inflammatory diseases through the suppression of NF-κB activation. However, the effect of IMD 0354 on bone homeostasis is unknown. In this study, we demonstrated that IMD 0354 significantly attenuated ovariectomy-induced bone loss and inhibited osteoclastogenesis in mice, whereas bone formation was not affected. Additionally, IMD 0354 dramatically inhibited osteoclast differentiation and function induced by RANKL and macrophage colony-stimulating factor in bone marrow monocytes as verified by tartrate-resistant acid phosphatase (TRAP) staining as well as bone resorption assay in vitro. Subsequently, we found that activation of NF-κB signaling and the ERK/c-Fos axis were blunted during osteoclast formation induced by RANKL. Transcription factors nuclear factor of activated T cells c1 (NFATc1) and c-Fos were suppressed with the decreased expression of osteoclast-related genes by IMD 0354. Our findings suggest that IMD 0354 could be a potential preventive and therapeutic drug for osteoporosis.

Modic changes are the MRI signal changes of degenerative lumbar vertebral endplate and which lead to or accelerate intervertebral disc degeneration. NLRP3, caspase-1, and interleukin-1β (IL-1β) play a pivotal role in the pathogenesis of many inflammatory diseases, such as osteoarthritis. However, the roles of IL-1β and its activators caspase-1 and NLRP3 are unclear in the degenerative endplate. We asked: (1) What are the degenerative changes of the histologic features and chondrogenic markers’ gene expressions between the cartilaginous endplates of patients with Modic changes and trauma (control)? (2) How does the NLRP3/caspase-1/IL-1β axis in the cartilaginous endplates of patients with Modic changes compare with control (trauma) specimens? Surgical specimens of cartilaginous endplates were divided into Modic changes (n = 56) and the trauma control (n = 16) groups. Hematoxylin and eosin and safranin O staining of cartilaginous endplate tissues were done to evaluate the extracellular matrix. Reverse transcription-polymerase chain reaction was performed on these tissues to investigate mRNA expression of type II collagen (Col II), SOX-9, matrix metalloproteinase-3, and a disintegrin like and metalloproteinase thrombospondin type I motifs-5. NLRP3, caspase-1, and IL-1β were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Hematoxylin and eosin and safranin O staining showed the extracellular matrix degraded in the cartilaginous endplates of patients with Modic changes but not in the control cartilaginous endplates. Chondrogenic Col II (p = 0.024) and SOX9 (p = 0.053) were downregulated in the Modic changes group compared with the control group. In contrast to the control group, the transcriptional levels of NLRP3 (p < 0.001), caspase-1 (p = 0.054), and IL-1β (p = 0.001) were all upregulated in the Modic changes group. The expression of NLRP3, caspase-1, and IL-1β was upregulated in the patients with low back pain and Modic changes on MRI compared with patients with vertebral burst fracture without degenerative changes on MRI. The data suggest the NLRP3/caspase-1/IL-1β axis may be implicated in lumbar cartilaginous endplate degeneration. The NLRP3/caspase-1/IL-1β axis is active in cartilaginous endplates of patients with Modic changes and inflammatory cascades can exacerbate the cartilaginous endplate degeneration which may act as a trigger for intervertebral disc degeneration and low back pain. If these findings can be confirmed by others, we hope that new and effective therapy could be developed directed against this target.

In this paper, we carried out a randomized controlled clinical trial to explore the effect of 12-words-for-life-nurturing exercise on patients presenting with cervical spondylosis. After exercise intervention, the mean VAS and NDI scores of the patients decreased significantly and the scores of BP, VT, and MH in SF-36 Health Questionnaire were significantly higher. Exercise therapy showed significant effect on relieving pain and improving vitality and mental health. The 12-words-for-life-nurturing exercise may be a potential effective therapy for patients with cervical spondylosis.

In this paper, orange peel was utilized as low-cost adsorbent to remove carbofuran from aqueous solution by adsorption. All the experiments were conducted at 30°C to investigate the effects of initial concentration, adsorbent dosage, contact time, ionic strength, and pH on carbofuran adsorption. The results showed that it was effective to remove carbofuran in the alkalic medium and the equilibrium adsorption was practically achieved in 60 min. The presence of NaCl inhibited the adsorption of carbofuran onto orange peel. Langmuir model provided the better correlation of the experimental data and could interpret the adsorption process and the maximum monolayer adsorption capacity was found to be 84.49 mg/g at the temperature of 30°C. The pseudo-second-order kinetic model could describe the adsorption kinetics rationally and the rate-limiting step was the intraparticle diffusion process. It was implied that orange peel may be suitable as adsorbent material for adsorption of N-methyl carbamate insect...

The aim of this study was to evaluate early ASD at short-term follow-up in fused and unoperated patients with degenerative disc disease, using quantitative magnetic resonance imaging (MRI) analysis of the area, signal intensity and their product, i.e., MRI index of the central bright area of the disc as well as measures of intervertebral disc height and Pfirrmann grading scale. The further purpose was to determine whether fusion accelerates ASD compared with non-surgical treatment in short-term follow-up.One hundred and eight chronic low back patients diagnosed as L4/L5 degeneration undertook either one-level instrumented posterior lumbar interbody fusion or conservative treatment. They were followed up for about 1 year. Finally 46 fused and 45 conservatively treated patients with MRI follow-up were included. Pre- and post-treatment MRIs were compared to determine the progression of disc degeneration at the two cranial adjacent segments.The area, signal intensity and MRI index of the central bright area of the adjacent discs decreased in the operated and unoperated groups from pre-treatment to follow-up, except for an insignificant decrease of signal intensity at the second adjacent segment in the unoperated group. The changes in these parameters were statistically greater at the first than the second adjacent segment in the fused group, but not in the unoperated group. And the changes in the fused group were more pronounced than those at both neighbouring levels in the unoperated group. However, the Pfirrmann grading scale and intervertebral disc height did not detect any changes at adjacent discs in either group.Decrease in the parameters of quantitative MRI analysis indicated early degeneration at discs adjacent to lumbar spinal fusion. Fusion had an independent effect on the natural history of ASD during short-term follow-up. Continued longitudinal follow-up is required to determine whether these MRI changes lead to pathologic changes.

Adsorption of cefradine onto peanut husk from aqueous solution was investigated in the paper. All the experiments were conducted at the same adsorbent dose (1.0 g/ml) and the same temperature of 293 K to investigate the effects of initial concentration of cefradine, contact time, ionic strength and solution pH. The results showed that it was effective to remove cefradine in the acidic medium and the equilibrium adsorption was practically achieved in 60 min. The presence of NaCl or MgCl2 inhibited the adsorption of cefradine onto peanut husk, while the presence of CaCl2 enhanced the adsorption capacity. The pseudo-second order kinetic equations could describe the adsorption kinetics rationally and the rate-limiting step was the intraparticle diffusion process. The Langmuir model provided the best correlation of the experimental data and could interpret the adsorption process and the Langmuir adsorption capacity was found to be 35.73 mg/g. Chemical modification of peanut husk could help to improve ...

The native and chemically modified corncobs were utilized as low-cost and efficient adsorbent to remove bromate from aqueous solution in this study. The parameters of the adsorbent i.e. adsorption capacity, selectivity, regenerability were investigated. All the experiments were conducted at the same adsorbent dose (0.2 g/200 ml) and the same temperature of 30°C to investigate the effects of initial concentration of bromate, contact time, ionic strength and solution pH, then the optimal experimental conditions were ascertained. The results showed that the optimum conditions for the removal of bromate were at the aqueous solution with low ion concentration, pH of about 9.0 and equilibrium time of 80 min, respectively. Freundlich model fi tted the adsorption data quite reasonably (R2 > 0.92) and the maximum adsorption capacity was 101.01 mg/g. The experimental data followed the pseudo-second-order kinetic model very well. In addition, the removal percentages (%) of bromate by corncob modifi ed by 80% isoprop...

Objective: To determine differences in paraspinal muscle injury between a modified minimally invasive approach (MMIA) and a traditional operative approach (TOPA) for one-level instrumented posterior lumbar inter-body fusion (PLIF). Methods: From March 2006 to May 2008, a consecutive series of 91 patients who underwent a one-level instrumented PLIF procedure using one of two different approaches (MMIA in 41 patients and TOPA in 50), and who were operated on by one group of surgeons at a single institution, was studied. The following data were compared between the two groups: surgical time, blood loss, and changes in postoperative serum concentration of creatinine kinase (CK). More than 1 year post operation, low back pain was evaluated by a visual analog scale (VAS) and the Oswestry disability index (ODI). Some patients were also evaluated by MRI to allow comparison of the preoperative and postoperative cross sectional area (CSA) and fat degeneration grades at the operative level. Results: There was no statistically significant difference in surgical time, but blood loss, serum concentration of CK, and scores of the VAS and ODI were markedly less in the MMIA group compared with the TOPA group. In the TOPA group, the postoperative CSA of the multifidus muscles was significantly smaller than it was pre-operatively. In contrast, there was no significant difference between the pre- and post-operative CSA of the multifidus muscles in the MMIA group. There was more fatty infiltration postoperatively than preoperatively in both the TOPA and MMIA groups, the increase in fatty infiltration being greater in the TOPA than in the MMIA group. Conclusion: Compared with TOPA, MMIA can significantly lessen paraspinal muscle injury, and reduce the incidence of low back pain.

We set out to determine whether a minimally invasive approach for one-level instrumented posterior lumbar interbody fusion reduced undesirable changes in the multifidus muscle, compared to a conventional open approach. We also investigated associations between muscle injury during surgery (creatinine kinase levels), clinical outcome and changes in the multifidus at follow-up. We studied 59 patients treated by one team of surgeons at a single institution (minimally invasive approach in 28 and conventional open approach in 31, voluntarily chosen by patients). More than 1 year postoperatively, all the patients were followed up with the visual analogue scale (VAS) and Oswestry disability index (ODI), and 16 patients from each group were evaluated using MRI. This enabled the cross-sectional area (CSA) of lean multifidus muscle, and the T2 signal intensity ratio of multifidus to psoas muscle, to be compared at the operative and adjacent levels. The minimally invasive group had less postoperative back pain (P

The adsorption equilibria of single-component and binary mixtures of levulinic/formic acids in the aqueous solution on three different types of basic polymeric adsorbents were experimentally measured at 30 °C. Adsorption isotherms such as Langmuir, Freundlich and Sips were applied to correlate the single-solute adsorption data. Results demonstrated that the adsorption isotherms of both acids on all three adsorbents were best described by the Sips model, and that formic acid has higher adsorption capacity and stronger affinity on all three resins. The adsorption of binary mixtures of formic/levulinic acids reveals that formic acid is preferentially adsorbed and levulinic acid can be competitively displaced by formic acid. Binary Sips model and the ideal adsorbed solution (IAS) theory were employed to simulate the binary competitive adsorption data. The binary Sips model cannot predict the competitive adsorption behavior. The IAS model was successfully coupled with Sips isotherm parameters determined from single-component adsorption data to predict the binary competitive adsorption behavior of levulinic/formic acids on all three resins.

// Xianfeng Lin 1,2,* , Xiangqian Fang 1,2,* , Qiang Wang 1,2,* , Zhijun Hu 1,2 , Kai Chen 3 , Zhi Shan 1 , Shuai Chen 1,2 , Jiying Wang 1,2 , Jian Mo 1,2 , Jianjun Ma 1,2 , Wenbing Xu 1,2 , An Qin 4 and Shunwu Fan 1,2 1 Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China 2 Institute of Micro-Invasive Surgery of Zhejiang University, Hangzhou, China 3 Department of Orthopaedic Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China 4 Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China * These authors have contributed equally Correspondence to: Shunwu Fan, email: // An Qin, email: // Keywords : intervertebral disc, decellularization, extracellular matrix, disc degeneration, mesenchymal stem cell, Pathology Section Received : November 26, 2015 Accepted : February 18, 2016 Published : February 25, 2016 Abstract Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo . Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro . Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro . Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo . In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases.

Osteoclasts play an important role in diseases involving bone loss. In this study, we assessed the effect of a plant-derived natural alkaloid (lycorine, or LY) on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis could be inhibited by LY; this effect was due to inhibition of mitogen-activated protein kinase (MAPK) signalling via MAP kinase kinases (MKKs). The MAPK agonist anisomycin could partially rescue the inhibitory effect of LY. Furthermore, LY also played a protective role in both a murine ovariectomy (OVX)-induced osteoporosis model and a titanium particle-induced osteolysis model. These results confirmed that LY was effective in preventing osteoclast-related diseases in vivo. In conclusion, our results show that LY is effective in suppressing osteoclastogenesis and therefore could be used to treat OVX-induced osteoporosis and wear particle-induced osteolysis.

Supplemental Digital Content is available in the text, Background: There is a lack of high-quality evidence supporting the use of manipulation therapy for patients with cervical radiculopathy (CR). This study aimed to evaluate the effectiveness of Shi-style cervical manipulations (SCMs) versus mechanical cervical traction (MCT) for CR. Methods: This was a randomized, open-label, controlled trial carried out at 5 hospitals in patients with CR for at least 2 weeks and neck pain. The patients received 6 treatments of SCM (n = 179) or MCT (n = 180) over 2 weeks. The primary outcome was participant-rated disability (neck disability index), measured 2 weeks after randomization. The secondary outcomes were participant-rated pain (visual analog scale) and health-related quality of life (36-Item Short Form Health Survey [SF-36]). Assessments were performed before, during, and after (2, 4, 12, and 24 weeks) intervention. Results: After 2 weeks of treatment, the SCM group showed a greater improvement in participant-rated disability compared with the control group (P = .018). The SCM group reported less disability compared with the control group (P