Designing NIR AIEgens for lysosomes targeting and efficient photodynamic therapy of tumors.

Cancer is the most severe health problem facing most people today. Photodynamic therapy (PDT) for tumors has attracted attention because of its non-invasive nature, negligible adverse reactions, and high spatiotemporal selectivity. Developing biocompatible photosensitizers that can target, guide, and efficiently kill cancer cells is desirable in PDT. Here, two amphiphilic organic compounds, PS-I and PSS-II, were synthesized based on the D-π-A structure with a positive charge. The two AIEgens exhibited near-infrared emission, large Stokes shift, high 1O2 and O2-∙ generation efficiency, good biocompatibility, and photostability. They were co-incubated with cancer cells and eventually accumulated to lysosomes by cell imaging experiments. In vitro and in vivo experiments demonstrated that PS-I and PSS-II could effectively kill cancer cells and sufficiently inhibit tumor growth under light irradiation. PS-I had a higher fluorescence quantum yield in the aggregated state, which made it better for bio-imaging in imaging-guided photodynamic therapy. In contrast, PSS-II with a longer conjugated structure had more ROS generation to kill tumor cells under illumination, and the tumor growth inhibition of mice reached 71.95% during the treatment. No observable injury or undesirable outcomes were detected in the vital organs of the mice within the treatment group, suggesting that PSS-II/PS-I had a promising future in efficient imaging-guided PDT for cancer.

A near-infrared aggregation-induced emission photosensitizer targeting mitochondria for depleting Cu2+ to trigger light-activated cancer cells oncosis.

Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.

A near-infrared AIE fluorescent probe for accurate detection of sulfur dioxide derivatives and visualization of fingerprints.

In most biophysiological processes, sulfur dioxide (SO2) is an important intracellular signaling molecule that plays an important role. The change of SO2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging.

LY103, a pomalidomide derivative, alleviates taxol resistance in NSCLC via energy metabolism crosstalk and tumor microenvironment intervention.

In this study, we identified HIF 1α as a potential target for reversing taxol resistance in lung cancer by combining bioinformatics analysis with pharmacological analysis. Furthermore, pomalidomide derivative LY103 was also be synthesized by introducing an isatin analogue into the amino terminal ofpomalidomide, and it has a broad antitumor spectrum and showed excellent activity against A549/Taxol cells (IC50 = 6.33 ± 0.51 µM). The results of molecular docking showed that not only LY103 was inclined to bind to HIF 1α stably, it could also form multiple hydrogen bonds with VAL376, ASP256, ILE454, and GLU455 of HIF 1α even was reduced to LY103-NH2 by nitroreductase, which was further stabilized the complex formed by them, thereby inhibiting the activity of HIF 1α. LY103 was able to significantly induce DNA damage and inhibit angiogenesis. Concurrently, LY103 activated the immune response, reduced the expression of cytokines TNF-α, IL-6, and IL-1ß, thus might be inhibit the proliferation and metastasis of tumor cells. Pharmacological analysis proved that LY103 led to cell apoptosis through the mitochondrial pathway, and its combination with taxol significantly promoted this process. In general, the consumption of glutathione, the crosstalk of energy metabolism, and the improvement of the tumor microenvironment caused by LY103 eventually led to the decrease of ABCC1 protein expression and the drug resistance was reversed. The rational design of LY103 provided a basis for the application of nitro compounds in the treatment of hypoxic tumors and the reversal of taxol resistance.

An AIE luminogen targeting the endoplasmic reticulum inhibits cancer cell growth via multicellular organelle oxidative stress.

Organelle-targeted photodynamic therapy has been increasingly investigated in recent decades, but little attention has been paid to the damage caused to other non-primary target organelles during the course of action, even though these non-primary target organelles may play a substantial role in inhibiting the growth of cancer cells. In this contribution, we report an AIE-type strong endoplasmic reticulum-targeted luminogen (MTOQS) with a distorted structure, which is efficient in producing ROS both in cellular and non-cellular environment, causing an effective reduction of high levels of GSH and MDA in cancer cells through the efficient accumulation of intracellular ROS, and the levels of ATP, l-lactic acid, anti-apoptotic factor Bcl-2 and apoptotic protein caspase-3 were determined. Through the identification of these markers, it was evidenced that MTOQS-induced dual organelle oxidative stress could diminish the degree of oxidative phosphorylation and glycolysis in cancer cells and trigger an alteration in the culture environment of cancer cells, while causing damage to the endoplasmic reticulum and mitochondria through multiorganelle oxidative stress, turning on the pathway of apoptosis and consequently driving cancer cells to apoptosis.

MicroRNA-936 Targets JAG1 and Inhibits the Proliferation of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Investigating the underlying molecular mechanism is essential for the treatment and prognosis of HCC. Emerging evidence suggests that microRNAs (miRNAs) play pivotal roles in cancer progression. Down-regulation of miR-936 has been found in several cancers, which serves as a tumor suppressor to inhibit the development of cancers. However, the clinical significance and functional roles of miR-936 in HCC have not been determined. To explore this, the expression of miR-936 in HCC tissues and cells was detected by RT-qPCR. Cell Counting Kit-8 (CCK-8) assay, cell migration and cell cycle analysis were performed to evaluate the effects of miR-936 on the growth of HCC cells. The targets of miR-936 were predicted using the miRDB database and confirmed by luciferase reporter experiments. The protein expression of targets was determined by western blot. The results showed that miR-936 was significantly decreased in HCC tissues and cell lines. Low expression of miR-936 was associated with the advance progression and poor survival of HCC patients (P = 0.0036). Functional study revealed that overexpression of miR-936 inhibited the proliferation, migration (decreased to ∼0.26 fold) and induced cell cycle arrested in G1 phase (from 35.3% to 44.7%) of HCC cells. Additionally, miR-936 targeted the 3'-untranslated region (UTR) of jagged-1 (JAG1) and reduced the expression of JAG1 (decreased to ∼0.35 fold). JAG1 was found to be up-regulated in HCC tissues and was inversely correlated with the expression of miR-936 (Pearson r = -0.4633; P = 0.0007). The anti-cancer effects of miR-936 on the proliferation of HCC cells were partially reversed by the rescue of JAG1. Therefore, these results suggested that miR-936 might be a potential target for HCC treatment.

A hybrid therapeutic approach for decreasing postoperative complications in patients with adult lumbar degenerative scoliosis.

To decrease postoperative complications in patients with adult lumbar degenerative scoliosis (ALDS), short-segment fusion surgery was used in this study. However, the incidence of adjacent segment disease was found to be remarkable. Therefore, we applied the hybrid treatment (short-segment fusion for responsibility levels plus nonfusion stabilization of lumbar segments, which was called the Wallis system, for the proximal level) to patients enrolled into this study. The purpose of this study was to investigate the feasibility of a novel hybrid therapeutic approach for treating patients with ALDS.From January 2011 to January 2017, a retrospective study was conducted consisting of 16 patients with ALDS who were treated with hybrid treatment. All patients were treated with short-segment decompression and fusion for responsibility levels and nonfusion stabilization of lumbar segments for the proximal levels. The imaging outcomes were evaluated preoperatively and at the time of follow-up.The mean visual analog score for back pain decreased from 6.1 ±â€Š2.0 preoperatively to 2.1 ±â€Š0.7 at 2-year follow-up (P < .05), and the mean visual analog score for leg pain reduced from 8.1 ±â€Š0.6 preoperatively to 1.3 ±â€Š0.8 at 2-year follow-up (P < .05). The Oswestry disability index scores improved from 65.4 ±â€Š16.3% preoperatively to 18.3 ±â€Š5.6% at 2-year follow-up (P < .05). The mean Cobb angle was 22.1 ±â€Š6.2° preoperatively, and 13.8 ±â€Š6.8° at 2-year follow-up (P < .05). The lumbar lordosis changed from -40.4 ±â€Š14.8° to -43.5 ±â€Š11.2° at 2-year follow-up (P < .05). Solid fusion was achieved in all the patients, and no incidence of adjacent segment disease was noted as well.The proposed hybrid treatment for patients with ALDS can achieve favorable clinical outcomes and a lower incidence of ALDS. However, the correction of deformity is still limited that highlights the necessity of further study.

Limited correction of lumbar lordosis in the treatment of degenerative scoliosis.

BACKGROUND: Patients suffering from degenerative scoliosis (DS) were commonly associated with coronal and sagittal imbalance which made deformity correction surgery necessary. The study aimed to explore the efficacy and feasibility of the limited correction of lumbar lordosis (LL) in the treatment of patients with DS. METHODS: This was a retrospective study including 58 DS patients who underwent spinal deformity correction surgery and were followed up at least 2 years between January 2013 and January 2017. According to the difference of postoperative LL, the patients were divided into 2 groups: the limited correction group: Pelvic incidence(PI)-18°≤ LL .05). In terms of surgery, the limited group had less intra-operative blood loss and operation time (P < .05). At the last follow-up, significant differences were found in terms of LL(-38.2 ±â€Š4.7° and -46.9 ±â€Š4.7°), PT (18.8 ±â€Š5.2° and 11.1 ±â€Š3.6°), sacrum slope (33.7 ±â€Š7.0° and 41.4 ±â€Š6.1°) (P < .05), while there were no significant differences in terms of lumbar Cobb angle (10.5 ±â€Š9.3°and 8.3 ±â€Š6.7°), Oswestry Disability Index scores (25.6 ±â€Š10.2 and 26.4 ±â€Š12.1), and JOA scores (23.6 ±â€Š5.2 and 22.3 ±â€Š5.7) (P > .05). CONCLUSION: Limited correction of LL in the treatment of DS patients can achieve favorable clinical outcomes including effective Cobb angle correction with less blood loss and operative time.

The position of the aorta relative to the spine in patients with adult degenerative scoliosis.

STUDY DESIGN: A retrospective analysis was conducted to analyze the position of the aorta by MRI in patients with adult degenerative scoliosis. OBJECTIVE: This study aimed to investigate the relative anatomic positions of the aorta and spine in patients with adult degenerative scoliosis (ADS). Aorta injury is a rare complication of spinal surgeries. However, there would be a disastrous consequence once it happened. Therefore, knowing about the position of aorta is of great importance. METHODS: A retrospective analysis was performed in 90 patients with ADS and 132 participants without spine deformity. ADS patients were divided into several groups such as left scoliosis, left scoliosis with thoracolumbar kyphosis, right scoliosis, and right scoliosis with thoracolumbar kyphosis. The aorta-vertebrae angle (α) and aorta-vertebrae distance (d) in each level of T12-L4 were measured by using a Cartesian coordinate system. t test of independent samples was performed, α and d were compared, and Pearson correlation analysis was employed for α, d, and X-ray radiographic measurements. RESULT: The changes of α were not statistically significant (P > 0.05) in LS and LKS groups but d (P < 0.05) was longer in LKS group compared with the control group. In the right malformed group, there was no significant change in the angle (P > 0.05) in the abdominal aorta but longer d (P < 0.05) than the normal group. There was longer d in the RKS group compared with the RS group (P < 0.05). Pearson correlation analysis showed that there was a positive correlation between d and TLK (r = 0.439, P < 0.05). CONCLUSION: In patients with ADS, a relative normal position is maintained between the aorta and vertebrae. While the aorta is slightly away from the left pedicle in RS patients and farther away in patients with kyphosis, the angle of kyphosis would become bigger and d becomes longer. Therefore, the surgeons should be aware of the changes of the aorta position to avoid the disastrous vessel injuries.

Spontaneous Remodeling of Spinal Canal After Sagittal Translation in Pedicle Subtraction Osteotomy for Correction of Thoracolumbar Kyphosis in Ankylosing Spondylitis.

BACKGROUND: Sagittal translations (STs) secondary to osteotomy for the correction of ankylosing spondylitis (AS) kyphosis have drawn great attention, which is considered closely related to neurologic deficits and terrible fusion. Despite being discussed in several cases, there were no relevant reports about the transformation of ST and the spinal canal remodeling in AS patients. METHODS: Retrospective analysis was conducted on 16 patients with ST for the treatment of AS kyphosis through pedicle subtraction osteotomy during January 2011 to December 2014 in our hospital. Full-length free-standing spinal radiographs were available for all patients before and after surgery and also at the final follow-up. Radiologic parameters including global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA), and ST were measured. Rates of ST transformation after the surgery and at 1-year follow-up were compared. RESULTS: The average follow-up was 22 months, ranging from 12-36 months. There was no internal fixation failure during this period. The preoperative GK was 59.9 ± 21.0°, TLK was 38.0 ± 13.0°, LL was 7.4 ± 26.5°, and SVA was 27.2 ± 8.6 mm. The postoperative GK was 15.7 ± 2.1°, TLK was 5.6 ± 2.6°, LL was -36.1 ± 2.9°, and SVA was 6.1 ± 4.3 mm. ST was 7.1 ± 2.7 mm after surgery and 1.2 ± 1.0 mm at 1-year follow-up. The difference was statistically significant (P < 0.05). The rate of ST transformation was 84.9% ± 9.7%. According to Scoliosis Research Society surveys, the preoperative and the final follow-up satisfaction score was 1.6 ± 0.3 and 4.7 ± 0.4 respectively (P < 0.05). Remodeling of the spinal canal happened to all the patients with different degrees. CONCLUSIONS: All patients with ST after pedicle subtraction osteotomy for AS kyphosis occurred with spontaneous remodeling of the spinal canal at 1-year follow-up, by which ST can decrease in different degrees or even disappear, and favorable fusion can be achieved even without bone grafting into the osteotomy vertebra.

Melatonin receptor stimulation by agomelatine prevents Aß-induced tau phosphorylation and oxidative damage in PC12 cells.

PURPOSE: As a novel antidepressant drug, agomelatine has good therapeutic effect on the mood disorder and insomnia in Alzheimer's disease (AD). Recent studies have shown the neuroprotective function of agomelatine, including anti-oxidative and anti-apoptosis effect. However, it remains unclear whether agomelatine exerts neuroprotection in AD. Thus, the neuroprotective effect of agomelatine against amyloid beta 25-35 (Aß25-35)-induced toxicity in PC12 cells was evaluated in this study. METHODS: The concentration of malondialdehyde (MDA), LDH, and ROS was investigated to evaluate oxidative damage. The expression of P-tau, tau, PTEN, P-Akt, Akt, P-GSK3ß, and GSK3ß proteins was assessed by Western blotting. Our results demonstrated that Aß25-35 significantly increased the content of MDA, LDH, and ROS. Meanwhile, Aß25-35 upregulated the expression of P-tau and PTEN as well as downregulated P-Akt and P-GSK3ß expression. These effects could be blocked by agomelatine pretreatment. Furthermore, luzindole, the melatonin receptor (MT) antagonist, could reverse the neuroprotective effect of agomelatine. CONCLUSION: The results demonstrated that antidepressant agomelatine might prevent the tau protein phosphorylation and oxidative damage induced by Aß25-35 in PC12 cells by activating MT-PTEN/Akt/GSK3ß signaling. This study provided a novel therapeutic target for AD in the future.

Precision Treatment of Adult Lumbar Degenerative Scoliosis Complicated by Lumbar Stenosis with the Use of Selective Nerve Root Block.

BACKGROUND: Use of short-segment or long-segment fusion is controversial in treatment of adult lumbar degenerative scoliosis (ALDS). The aim of this study was to explore efficacy and feasibility of precision treatment of ALDS with selective nerve root block. METHODS: From January 2014 to January 2016, a retrospective study of 23 patients with ALDS treated with precision short-segment surgery with at least 2-year follow-up was performed. Fixation segment was determined by selective nerve root block. Visual analog scale and Oswestry Disability Index (ODI) were evaluated preoperatively and at 2-year follow-up. Radiographic measurements included Cobb angle of lumbar curve, lumbar lordosis, sacrum slope, and pelvic tilt. Radiographic evaluation of fusion integrity was performed based on Bridwell interbody fusion grading system at final follow-up. RESULTS: Mean follow-up time was 25.2 ± 1.4 months. Average lumbar curve was 21.6° ± 7.4° preoperatively and 11.2° ± 6.5° at final follow-up (P < 0.01), with correction rate of 48.1%. Lumbar lordosis changed from -37.1° ± 12.9° to -42.1° ± 10.5° at final follow-up (P < 0.01). Mean visual analog scale back pain scores decreased from 6.0 ± 1.8 preoperatively to 1.5 ± 0.8 at final follow-up (P < 0.01), and mean visual analog scale leg pain scores decreased from 8.1 ± 0.6 preoperatively to 1.3 ± 1.3 at final follow-up (P < 0.01). Oswestry Disability Index score improved from 60.9% ± 15.7% preoperatively to 22.1% ± 11.6% at final follow-up (P < 0.01). All patients achieved grade I fusion at final evaluation. One patient (4%) needed further surgical intervention. CONCLUSIONS: Precision treatment of ALDS with selective nerve root block can achieve favorable clinical outcomes and good fusion with less surgical injury and low complications. Deformity correction is limited, which requires further study.

Aging modulates microglia phenotypes in neuroinflammation of MPTP-PD mice.

As the crucial etiological factor, aging-related microglia activation promotes the development of Parkinson's disease (PD). However, the molecular and functional changes of aged-microglia and their contribution to neurodegeneration in PD are only partially understood, which was investigated in our study. Female C57BL/6 mice were randomly divided into four groups, included young-control group, young-MPTP group, aged-control group and aged-MPTP group. Pole test and adhesive removal test were firstly performed. ELISA assay was used to detect the content of interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) in brain tissue. Then we tested the expression of tyrosine hydroxylase (TH), p-nuclear transcription factor (NF-κB), toll-like receptor2 (TLR2), arginase-1 (arg-1), inducible nitric oxide synthase (iNOS) by western blot and immunofluorescence analysis. Our results showed that aging promoted M1 microglia activation and inhibited M2 microglia activation in SN in MPTP-PD model, accompanied by the elevation of proinflammatory cytokine (TNF-α and IL-1ß). Consequently, aging significantly aggravated motor dysfunction and dopaminergic neuron loss in SN. Besides, compared with young-MPTP group, the protein expression of TLR2 and p-NF-κB-p65 increased obviously in aged-MPTP group. The results revealed that aging aggravated inflammatory response by modulated microglia phenotypes transition in SN in PD, and contributed to further understand the pathogenesis of PD.

Can pelvic tilt be restored by spinal osteotomy in ankylosing spondylitis patients with thoracolumbar kyphosis? A minimum follow-up of 2 years.

BACKGROUND: Defining the postoperative pelvic tilt (PT) individually can help to reconstruct sagittal balance. However, the postoperative actual PT is hardly restored to theoretical value. Some cases with theoretical postoperative PT was overcorrected and still did not have normal horizontal visual field after surgery. The objective of this study is to describe the pelvic tilt change after spinal osteotomy in ankylosing spondylitis (AS) kyphotic deformity and evaluate the effect on clinical outcomes. METHODS: Twenty-three AS patients including 21 men and two women with thoracolumbar kyphosis, who underwent spinal osteotomy from 2013 to 2015 in our center, were retrospectively reviewed. A series of parameters including sacral slop (SS), pelvic incidence (PI), PT, and sagittal vertical axis (SVA) measured on preoperative and postoperative standing radiographs were analyzed. The theoretical postoperative PT (tPT) was calculated by the formula tPT = 0.37 × PI - 7. The radiographic measurements were compared before surgery, 2 weeks and at least 2 years postoperatively. Clinical outcomes were performed with the Oswestry disability index and Scoliosis Research Society-22 surveys. RESULTS: Mean age of the patients (2 women, 21 men) was 39.8 ± 9.1 years. Mean follow-up was 27.4 ± 3.8 months, at least 24 months. After spinal osteotomy, SS and SVA were corrected from 11.9° ± 11.2° and 18.0 ± 7.6 mm preoperatively to 25.8° ± 8.1° and 9.6 ± 6.3 mm postoperatively, respectively (p < 0.001). PT reduced from 37.6° ± 12.1° to 21.8° ± 9.8° postoperatively (p < 0.001). The tPT was different from postoperative actual PT significantly (p < 0.001). The clinical evaluations were not correlated with postoperative PT. CONCLUSION: The abnormal PT is corrected by spinal osteotomy but is hard to restore to theoretical normal value. PT is a helpful parameter in making surgery plan. But pursuing postoperative PT being totally equal to tPT is undesirable and even may cause for overcorrection.

Radiographic and clinical outcomes following MIS-TLIF in patients with adult lumbar degenerative scoliosis.

BACKGROUND: Patients suffering from adult lumbar degenerative scoliosis (ALDS) are commonly complicated with advanced age, osteoporosis, cardiopulmonary insufficiency, and some other medical comorbidity. Therefore, the traditional open surgery can lead to high rate of postoperative complications. The purposes of this study were to introduce our experiences and explore the efficacy and feasibility of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of patients with ALDS. METHODS: From January 2008 to January 2014, a retrospective study of 22 patients with ALDS treated with MIS-TLIF was followed up at least 2 years. All patients suffered from one-level lumbar stenosis, and the nerve root block was performed to make sure the exact level. The clinical and radiographic outcomes were evaluated preoperatively and at the time of 2-year follow-up. RESULTS: The mean visual analog scale (VAS) back pain scores decreased from 6.2 ± 1.8 preoperatively to 2.2 ± 0.7 at 2-year follow-up (P < 0.05), and the mean VAS leg pain scores decreased from 8.2 ± 0.7 preoperatively to 1.4 ± 1.4 at 2-year follow-up (P < 0.05). The Oswestry Disability Index score improved from 62.4 ± 16.1% preoperatively to 24.2 ± 9.3% at 2-year follow-up (P < 0.05). The average lumbar curve was 20.7° ± 7.0° preoperatively and 12.7° ± 7.1° at 2-year follow-up (P < 0.05). The lumbar lordosis changed from - 39.5° ± 13.6° to - 43.6° ± 10.6° at 2-year follow-up (P < 0.05). Solid fusion was achieved in all patients. CONCLUSION: The technique of MIS-TLIF can be used to treat the patients with ALDS whose symptom is mainly from one-level lumbar stenosis, achieving favorable clinical outcomes and good fusion, with less blood loss and complications.

Risk factor analysis of proximal junctional kyphosis after posterior osteotomy in patients with ankylosing spondylitis.

OBJECTIVE The aim of this paper was to analyze the incidence and risk factors of proximal junctional kyphosis (PJK) in patients with ankylosing spondylitis (AS) who underwent pedicle subtraction osteotomy. METHODS The records of 83 patients with AS and thoracolumbar kyphosis who underwent surgery at the authors' institution between 2007 and 2013 were reviewed. The patients were divided into 2 groups based on the presence or absence of PJK. The radiographic measurements, including proximal junctional angle (PJA), sagittal parameters, and pelvic parameters of these 2 groups, were compared at different time points: before surgery and 2 weeks, 12 months, and 2 years after surgery. Oswestry Disability Index scores were also evaluated. RESULTS Overall, 14.5% of patients developed PJK. Before surgery, the mean PJAs in the 2 groups were 13.6° and 8.5°, respectively (p = 0.008). There were no significant differences in age, sex, and body mass index between groups. Patients with PJK had a larger thoracolumbar kyphotic angle (50.8° ± 12.6°) and a greater sagittal vertical axis (21.7 ± 4.3 cm) preoperatively than those without PJK. The proportion of patients with PJK whose fusion extended to the sacrum was 41.2% (7/17), which is significantly greater than the proportion of patients with PJK whose lowest instrumented vertebra was above the sacrum. Oswestry Disability Index scores did not significantly increase in the PJK group compared with the non-PJK group. CONCLUSIONS The authors found that PJK occurs postoperatively in patients with AS with an incidence of 14.5%. Risk factors of PJK include larger preoperative sagittal vertical axis, PJA, and osteotomy angle. Reducing the osteotomy angle in some severe cases and extending fusion to a higher, flatter level would be also beneficial in decreasing the risk of PJK.

The inhibition of CB1 receptor accelerates the onset and development of EAE possibly by regulating microglia/macrophages polarization.

Cannabinoid 1 receptor (CB1R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB1R in the treatment of EAE by using a specific and selective CB1R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss. SR141716A significantly up-regulated the expression of toll like receptor-4 (TLR-4) and nuclear factor-kappaB/p65 (NF-κB/p65) on microglia/macrophages of EAE mice as well as levels of inflammatory factors (TNF-α, IL-1ß, IL-6) and chemokines (MCP-1, CX3CL1), accompanied by the shifts of cytokines from Th2 (IL-4, IL-10) to Th1 (IFN-γ)/Th17 (IL-17) in the spinal cords of EAE mice. Similar changes happened on splenic mononuclear cells (MNCs) except chemokine CX3CL1. Consistently, SR141716A promoted BV-2 microglia to release inflammatory factors (TNF-α, IL-1ß, IL-6) while inhibited the production of IL-10 and chemokines (MCP-1, CX3CL1). Furthermore, when splenic CD4+ T cells co-cultured with SR141716A-administered BV-2 microglia, the levels of IL-4 and IL-10 were decreased while production of IL-17 and IFN-γ increased significantly. Our research indicated that inhibition of CB1R induced M1 phenotype-Th17 axis changed of microglia/macrophages through TLR-4 and NF-κB/p65 which accelerated the onset and development of EAE. Therefore, CB1R may be a promising target for the treatment of MS/EAE, but its complexity remains to be carefully considered and studied in further clinical application.

Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic Papillary Thyroid Carcinoma.

MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect. STUDY DESIGN: A unique case report. OBJECTIVE: A three-dimensional (3D) printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma in a middle-age female patient. SUMMARY OF BACKGROUND DATA: Papillary thyroid carcinoma is a malignant neoplasm with a relatively favorable prognosis. A metastatic lesion in multilevel cervical spine (C2-C4) destroys neurological functions and causes local instability. Radical excision of the metastasis and reconstruction of the cervical vertebrae sequence conforms with therapeutic principles, whereas the special-shaped multilevel upper-cervical spine requires personalized implants. 3D printing is an additive manufacturing technology that produces personalized products by accurately layering material under digital model control via a computer. Reporting of this recent technology for reconstructing multilevel cervical spine (C2-C4) is rare in the literature. METHODS: Anterior-posterior surgery was performed in one stage. Radical resection of the metastatic lesion (C2-C4) and thyroid gland, along with insertion of a personalized implant manufactured by 3D printing technology, were performed to rebuild the cervical spine sequences. The porous implant was printed in Ti6AL4V with perfect physicochemical properties and biological performance, such as biocompatibility and osteogenic activity. Finally, lateral mass screw fixation was performed via a posterior approach. RESULTS: Patient neurological function gradually improved after the surgery. The patient received 11/17 on the Japanese Orthopedic Association scale and ambulated with a personalized skull-neck-thorax orthosis on postoperative day 11. She received radioiodine I therapy. The plane x-rays and computed tomography revealed no implant displacement or subsidence at the 12-month follow-up mark. CONCLUSION: The presented case substantiates the use of 3D printing technology, which enables the personalization of products to solve unconventional problems in spinal surgery. LEVEL OF EVIDENCE: 5.

Effect and Strategy of 1-stage Interrupted 2-level Transpedicular Wedge Osteotomy for Correcting Severe Kyphotic Deformities in Ankylosing Spondylitis.

STUDY DESIGN: Prospective study. OBJECTIVE: To investigate the safety, outcome, and strategy of the 1-stage interrupted 2-level transpedicular wedge osteotomy for correcting the severe kyphotic deformity in ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: There has been a large series in the literature reporting on results of osteotomy for the correction of kyphotic deformity secondary to AS. However, few articles have reported, in detail, the plan, design, strategy, and effect of 1-stage interrupted 2-level transpedicular wedge osteotomy for the correction of severe kyphotic deformity in AS. MATERIALS AND METHODS: From May 2003 to February 2010, 24 consecutive patients, 17 males and 7 females, suffering from AS with severe spinal kyphosis, underwent 1-stage interrupted 2-level transpedicular wedge osteotomy in our hospital by the corresponding author. Improvements in relevant parameters were recorded and clinical results were evaluated. RESULTS: The average operating time was 282±43 minutes, and the average blood loss was 2202±737 mL. All the global and regional spinal alignments improved to relatively normal status: the global thoracolumbar kyphosis angle improved from 101.5±10.8 to 24.8±5.8 degrees (P<0.001), the thoracolumbar kyphosis improved from 37.9±5.1 to 0.7±12.8 degrees (P<0.001), and the lumbar lordosis improved from 35.0±9.2 to -25.7±10.9 degrees (P<0.001). Meanwhile, the chin-brow vertical angle improved from 79.5±5.1 to 8.5±2.7 degrees (P<0.001), and the sagittal imbalance distance improved from 49.6±6.5 to 11.5±3.5 cm (P<0.001). All the patients could walk with horizontal vision and lie on their backs postoperatively, and scoliosis research society-22 scores improved from 1.6±0.2 preoperatively to 4.3±0.2 at the 2-year follow-up. The mean time of follow-up was 52±28 months. Fusion of the osteotomy was achieved in each patient and no instances of loss of correction or implant failure were noted. CONCLUSION: For correcting severe kyphosis in patients with AS, the 1-stage interrupted 2-level transpedicular wedge osteotomy is a safe and effective technique that significantly improves appearance and function.

Posterior wedge osteotomy and debridement for Andersson lesion with severe kyphosis in ankylosing spondylitis.

BACKGROUND: Andersson lesion is a well-known complication in ankylosing spondylitis. Recently, owing to the worry about the healing of fracture, some scholars advocated additional anterior surgery or other procedures were necessary, which increase the risk of the nerve injury. The purpose of this study is to introduce our experience and to explore the efficacy and feasibility of posterior wedge osteotomy and debridement through Andersson Lesion for surgical treatment of severe kyphosis in ankylosing spondylitis. METHODS: From January 2012 to January 2014, a retrospective study of 14 Andersson lesion patients with severe kyphosis in ankylosing spondylitis treated with surgery was completed with an at least 2-year follow-up. The debridement procedure, before posterior wedge osteotomy in posterior approach, must scrape all sclerosis bone until healthy cancellous bone appears. Radiographic and clinical results and complications were assessed with an average follow-up of 24 months. The CT scan was obtained preoperatively and at the final follow-up to assess the displacement of the fracture preoperatively, the safety of screw insertion, the healing of the fracture at the final follow-up. The Bridwell interbody fusion grading system was used to assess the healing of the fracture. RESULTS: Local kyphosis was substantially corrected from 51.7 ± 15.6 to 7.1 ± 19.5, with a mean correction of 44°. The global kyphosis (GK) changed from 60.6 ± 28.3 to 20.3 ± 10.3 (P = 0.000). The mean VAS back pain scores decreased from 6.7 ± 0.8 preoperatively to 0.75 ± 0.6 after a 2-year follow-up (P = 0.000). The ODI score improved from 60.56 ± 15.1% preoperatively to 23.46 ± 8.2% after a 2-year follow-up (P = 0.000). The CT scan showed solid fusion at the level of the AL, and no internal fixation loose. All patients achieved grade 1 fusion. No major complication occurred. CONCLUSIONS: The posterior wedge osteotomy and debridement through AL can be used to correct the severe kyphosis in ankylosing spondylitis, achieving favorable clinical outcomes, good fusion, and satisfactory deformity correction.