Clinical Outcomes of Percutaneous Transforaminal Endoscopic Discectomy Assisted with Selective Nerve Root Block for Treating Radicular Pain with Diagnostic Uncertainty in the Elderly.

Purpose: To investigate the clinical outcomes of percutaneous transforaminal endoscopic discectomy assisted with selective nerve root block for treating radicular pain with diagnostic uncertainty in the elderly. Methods: A total number of 36 elderly patients were included in the study. Clinical outcomes collected for analysis include operative time, hospital stay time, Visual Analog Scale, and Oswestry Disability Index before and after the surgery, the global outcome based on the Macnab outcome criteria. Results: Seventeen males and nineteen females with a mean age of 73.72 ± 7.15 were included in this study. Radicular pain was the main complaint of all the patients with the least symptom duration of two months. Radiological findings showed that 80.6% of the patients with multilevel disc herniation, 16.7% received lumbar fusion surgery before, and 8.3% with degenerative scoliosis. Besides, 69.4% of the patients have at least one comorbidity. 85.4% of the patients showed a positive response to selective nerve root block, and 91.6% of the patients reported a favorable outcome at the last follow-up. The mean value of pre-operative leg pain was 7.56 ± 0.74 and dramatically decreased after surgery (2.47 ± 0.81, P < 0.001). Besides, the mean value of Oswestry Disability Index decreased from 43.03 ± 4.43 to 5.92 ± 5.24 (P < 0.001) one year after the surgery. Conclusion: Multilevel degeneration of the lumbar spine is common in elderly patients. Identifying the responsible segment and decompressing the nerve root through minimally invasive surgery can provide a satisfactory clinical outcome for those with radicular pain as their primary complaint. And selective nerve root block is a reliable diagnostic tool for those with an ambiguous diagnosis.

Comparison of the clinical outcomes of VBE-TLIF versus MIS-TLIF for single-level degenerative lumbar diseases.

OBJECTIVE: This research aims to compare the clinical outcomes of VBE-TLIF and MIS-TLIF for the treatment of patients with single-level degenerative lumbar diseases. METHODS: Ninety patients were enrolled in this study. The estimated blood loss, operation time, postoperative hospitalization days, time to functional exercise, amount of surgical drain and inflammatory index were recorded. The visual analog scale, Oswestry dysfunction index and modified MacNab criteria were used to assessed the patient's back and leg pain, functional status and clinical satisfaction rates. RESULTS: The average operation time of the VBE-TLIF group was longer than that of the MIS-TLIF group. The time for functional exercise, length of hospital stay, estimated blood loss and amount of surgical drain in the VBE-TLIF group were relative shorter than those in the MIS-TLIF group. Additionally, the levels of CRP, neutrophil, IL-6 and CPK in the VBE-TLIF group were significantly lower than those in the MIS-TLIF group at postoperative days 1 and 3, respectively (P < 0.001). Patients undergoing VBE-TLIF had significantly lower back VAS scores than those in the MIS-TLIF group on postoperative days 1 and 3 (P < 0.001). No significant differences were found in the clinical satisfaction rates (95.83 vs. 95.24%, P = 0.458) or interbody fusion rate (97.92 vs. 95.24%, P = 0.730) between these two surgical procedures. CONCLUSIONS: Both VBE-TLIF and MIS-TLIF are safe and effective surgical procedures for patients with lumbar diseases, but VBE-TLIF technique is a preferred surgical procedure with merits of reduced surgical trauma and quicker recovery.

Amorphous 1-D nanowires of calcium phosphate/pyrophosphate: A demonstration of oriented self-growth of amorphous minerals.

Amorphous inorganic solids are traditionally isotropic, thus, it is believed that they only grow in a non-preferential way without the assistance of regulators, leading to the morphologies of nanospheres or irregular aggregates of nanoparticles. However, in the presence of (ortho)phosphate (Pi) and pyrophosphate ions (PPi) which have synergistic roles in biomineralization, the highly elongated amorphous nanowires (denoted ACPPNs) form in a regulator-free aqueous solution (without templates, additives, organics, etc). Based on thorough characterization and tracking of the formation process (e.g., Cryo-TEM, spherical aberration correction high resolution TEM, solid state NMR, high energy resolution monochromated STEM-EELS), the microstructure and its preferential growth behavior are elucidated. In ACPPNs, amorphous calcium orthophosphate and amorphous calcium pyrophosphate are distributed at separated but close sites. The ACPPNs grow via either the preferential attachment of ∼2 nm nanoclusters in a 1-dimension way, or the transformation of bigger nanoparticles, indicating an inherent driving force-governed process. We propose that the anisotropy of ACPPNs microstructure, which is corroborated experimentally, causes their oriented growth. This study proves that, unlike the conventional view, amorphous minerals can form via oriented growth without external regulation, demonstrating a novel insight into the structures and growth behaviors of amorphous minerals.

RNA N6-methyladenosine demethylase FTO inhibits glucocorticoid-induced osteoblast differentiation and function in bone marrow mesenchymal stem cells.

Excess glucocorticoids (GCs) have been reported as key factors that impair osteoblast (OB) differentiation and function. However, the role of RNA N6-methyladenosine (m6 A) in this process has not yet been elucidated. In this study, we report that both the mRNA and protein expression of fat mass and obesity-associated gene (FTO), a key m6 A demethylase, were dose-dependently downregulated during OB differentiation by dexamethasone (DEX) in bone marrow mesenchymal stem cells (BMSCs), and FTO was gradually increased during OB differentiation. Meanwhile, FTO knockdown suppressed OB differentiation and mineralization, whereas overexpression of wide-type FTO, but not mutant FTO (mutated m6 A demethylase active site), reversed DEX-induced osteogenesis impairment. Interfering with FTO inhibited proliferation and the expression of Ki67 and Pcna in BMSCs during OB differentiation, whereas forced expression of wide-type FTO improved DEX-induced inhibition of BMSCs proliferation. Moreover, FTO knockdown reduced the mRNA stability of the OB marker genes Alpl and Col1a1, and FTO-modulated OB differentiation via YTHDF1 and YTHDF2. In conclusion, our results suggest that FTO inhibits the GCs-induced OB differentiation and function of BMSCs.

Research hotspots and trends on spinal cord stimulation for pain treatment: a two-decade bibliometric analysis.

Background: Chronic pain poses a significant social burden. Spinal cord stimulation (SCS) is considered to be the most promising treatment for refractory pain. The aim of this study was to summarize the current research hotspots on SCS for pain treatment during the past two decades and to predict the future research trends by bibliometric analysis. Methods: The literature over the last two decades (2002-2022) which was related to SCS in pain treatment was obtained from the Web of Science Core Collection. Bibliometric analyses were conducted based on the following aspects: (1) Annual publication and citation trends; (2) Annual publication changes of different publication types; (3) Publications and citations/co-citations of different country/institution/journal/author; (4) Citations/co-citation and citation burst analysis of different literature; and (5) Co-occurrence, cluster, thematic map, trend topics, and citation burst analysis of different keywords. (6) Comparison between the United States and Europe. All analyses were performed on CiteSpace, VOSviewer, and R bibliometrix package. Results: A total of 1,392 articles were included in this study, with an increasing number of publications and citations year by year. The most highly published type of literature was clinical trial. United States was the country with the most publications and citations; Johns Hopkins University was the institution with the most publications; NEUROMODULATION published the most papers; the most published author was Linderoth B; and the most cited paper was published in the PAIN by Kumar K in 2007. The most frequently occurring keywords were "spinal cord stimulation," "neuropathic pain," and "chronic pain," etc. Conclusion: The positive effect of SCS on pain treatment has continued to arouse the enthusiasm of researchers in this field. Future research should focus on the development of new technologies, innovative applications, and clinical trials for SCS. This study might facilitate researchers to comprehensively understand the overall perspective, research hotspots, and future development trends in this field, as well as seek collaboration with other researchers.

Minimally invasive transforaminal lumbar interbody fusion by a novel two-medium compatible bichannel endoscopy system, technique note and preliminary clinical results.

PURPOSE: Our team designed a novel two-medium compatible bichannel endoscopy system for spinal surgery, V-shape bichannel endoscopy (VBE) system. Hereby, this study will introduce minimally invasive transforaminal lumbar interbody fusion (TLIF) with VBE system and report its preliminary clinical results. METHODS: Fifty-two participants, who accepted VBE-assisted TLIF surgery (VBE-TLIF) in our hospital were included in this study. The duration of operation, off-bed time, and days of hospitalization were recorded. Besides, the patient's preoperative and postoperative pain were evaluated via visual analog scale (VAS), the functional status was evaluated via Oswestry dysfunction index (ODI) and modified MacNab criteria. Patients were asked to follow-up in the outpatient department at the 3rd, 6th, 12th, and 24th month after surgery. X-ray or CT was examined to evaluate the internal fixation position and interbody fusion result. RESULTS: All patients received unilateral decompression with an average operation duration of 178.49 ± 27.49 min. After the surgery, their VAS score of leg pain and back pain reduced significantly. At the last follow-up, the VAS score of leg pain and back pain was 0.80 ± 0.69 and 0.86 ± 0.75 separately. The difference shows statistically significant with p < 0.05. At the last follow-up, the ODI was 15.20 ± 5.75. According to modified MacNab criteria, 39 patients rated their function as excellent, and 10 patients were good. The overall satisfaction rate reached 94%. CONCLUSION: The VBE system reported in the current study can complete TLIF surgery safely and effectively.

Novel Nomograms and Web-Based Tools Predicting Overall Survival and Cancer-specific Survival of Solitary Plasmacytoma of the Spine.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: This study aimed to establish nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with solitary plasmacytoma of the spine (SPS). SUMMARY OF BACKGROUND DATA: SPS is a rare type of malignant spinal tumor. A systematic study of prognostic factors associated with survival can provide guidance to clinicians and patients. Consideration of other causes of death (OCOD) in CSS will improve clinical practicability. METHODS: A total of 1078 patients extracted from the SEER database between 2000 and 2018 were analyzed. Patients were grouped into training and testing data sets (7:3). Factors associated with OS and CSS were identified by Cox regression and competing risk regression, respectively, for the establishment of nomograms on a training data set. The testing data set was used for the external validation of the performance of the nomograms using calibration curves, Brier's scores, C-indexes, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA). RESULTS: Age and grade were identified as factors associated with both OS and CSS, along with marital status, radiation for OS, and chemotherapy for CSS. Heart disease, cerebrovascular disease, and diabetes mellitus were found to be the 3 most common causes of OCOD. The nomograms showed satisfactory agreement on calibration plots for both training and testing data sets. Integrated Brier score, C-index, and overall area under the curve on the testing data set were 0.162/0.717/0.789 and 0.173/0.709/0.756 for OS and CSS, respectively. DCA curves showed a good clinical net benefit. Nomogram-based web tools were developed for clinical application. CONCLUSION: This study provides evidence for risk factors and prognostication of survival in SPS patients. The novel nomograms and web-based tools we developed demonstrated good performance and might serve as accessory tools for clinical decision-making and SPS management. LEVEL OF EVIDENCE: 3.

Web-Based Nomograms for Overall Survival and Cancer-Specific Survival of Bladder Cancer Patients with Bone Metastasis: A Retrospective Cohort Study from SEER Database.

BACKGROUND: Our study aimed to explore the prognostic factors of bladder cancer with bone metastasis (BCBM) and develop prediction models to predict the overall survival (OS) and cancer-specific survival (CSS) of BCBM patients. METHODS: A total of 1438 patients with BCBM were obtained from the SEER database. Patients from 2010 to 2016 were randomly divided into training and validation datasets (7:3), while patients from 2017 were divided for external testing. Nomograms were established using prognostic factors identified through Cox regression analyses and validated internally and externally. The concordance index (C-index), calibration plots, and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the discrimination and calibration of nomogram models, while decision curve analyses (DCA) and Kaplan-Meier (KM) curves were used to estimate the clinical applicability. RESULTS: Marital status, tumor metastasis (brain, liver, and lung), primary site surgery, and chemotherapy were indicated as independent prognostic factors for OS and CSS. Calibration plots and the overall C-index showed a novel agreement between the observed and predicted outcomes. Nomograms revealed significant advantages in OS and CSS predictions. AUCs for internal and external validation were listed as follows: for OS, 3-month AUCs were 0.853 and 0.849; 6-month AUCs were 0.873 and 0.832; 12-month AUCs were 0.825 and 0.805; for CSS, 3-month AUCs were 0.849 and 0.847; 6-month AUCs were 0.870 and 0.824; 12-month AUCs were 0.815 and 0.797, respectively. DCA curves demonstrated good clinical benefit, and KM curves showed distinct stratification performance. CONCLUSION: The nomograms as web-based tools were proved to be accurate, efficient, and clinically beneficial, which might help in patient management and clinical decision-making for BCBM patients.

The synergetic effect of a gold nanocluster-calcium phosphate composite: enhanced photoluminescence intensity and superior bioactivity.

Gold nanoclusters (AuNCs) are a unique class of materials that exhibit visible luminescence. Amorphous calcium phosphate (ACP) is a widely used biomaterial for a variety of purposes, such as drug delivery, bone cementing, and implant coatings. In this study, a nanocomposite of AuNCs and ACP is prepared by biomimetic mineralization in a Dulbecco's modified Eagle's medium (DMEM). The strong interaction between AuNCs and Ca2+ ions effectively induces aggregation of AuNCs. The as-formed nanocomposite, AuNCs@ACP, emits significantly enhanced luminescence compared to AuNCs alone. The luminescence enhancement mechanism is investigated using synchrotron X-ray absorption fine structure spectroscopy. In addition, the presence of AuNCs stabilizes ACP and also enhances the biocompatibility of ACP in promoting cell proliferation, and the nanocomposites are promising as nanoprobes for cancer therapy and/or bone tissue engineering.

Sagittal alignment of the cervical spine: radiographic analysis of 111 asymptomatic adolescents, a retrospective observational study.

PURPOSE: To describe the cervical spine morphology and explore its relationship to global sagittal alignment parameters in the asymptomatic adolescent population.  METHODS: A total of 111 adolescent subjects were included. Sagittal alignment parameters, including C7 Slope, C2-C7 Cobb, C2-7 plumb line (PL), C2-S1 Sagittal Vertical Axis (SVA), C7-S1 SVA, T5-12 Cobb, T10-L2 Cobb, L1-S1 Cobb, pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS), were obtained from lateral radiographs.  RESULTS: Forty-four males and sixty-seven females with a mean age of 16.12 ± 2.40 years were included in this study. The mean values of C7 Slope, C2-7 Cobb and C2-7PL were 20.45 ± 8.88°, -7.72 ± 12.10°, and 13.53 ± 11.63 mm, respectively. C2-7 Cobb, C7 Slope showed significant differences between the male and female groups. Correlation analysis showed that C7 slope was significantly correlated with C2-7 Cobb (r = -0.544, P < 0.001), C2-S1 SVA (r = 0.335, P < 0.001), and C7-S1 SVA (r = 0.310, P = 0.001), but not lumbosacral parameters(L5-S1 Cobb, PI, PT, SS). Using a modified method of Toyama to describe the cervical spine morphology, there were 37 cases (33.3%) in the Lordotic group, and C7 slope, C2-7 Cobb and C2-7PL showed significant differences between groups. According to C2-C7 Cobb, there were 80 Lordotic cases (72.1%). C7 slope and C2-7PL were significantly different between the two groups. CONCLUSION: The cervical spine morphology of asymptomatic adolescents varies widely, from lordotic to kyphotic. Combining different classification methods provides a better understanding of the morphology of the cervical spine. C7 slope is an important predictor of global sagittal balance and C2-7PL is a key parameter for restoring cervical lordosis, which should be considered pre-operatively and for conservative treatment. Cervical regional sagittal alignment parameters are not correlated with lumbosacral parameters, and C2-7 Cobb, C7 Slope showed significant differences between males and females.

Mineralized Enzyme-Based Biomaterials with Superior Bioactivities for Bone Regeneration.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

CRISPR-Cas9-mediated loss of function of ß-catenin attenuates intervertebral disc degeneration.

Intervertebral disc degeneration is a very common medical condition causing pain and disability, and it cannot be reversed by available treatment options. Here we report that targeting ß-catenin, a pivotal factor associated with disc degeneration, ameliorates disc degeneration in a mouse model of disc injury. Degenerative changes in the disc in response to disc injury include decompression of nucleus pulposus (NP), replacement of notochordal cells in the NP by chondrocyte-like cells, and disorganization of annulus fibrosus (AF). Importantly, downregulation of ß-catenin through intradiscal injection of CRISPR-Cas9-expressing adeno-associated virus significantly mitigated all these pathological changes, by preserving notochordal cells and attenuating chondro-osteogenesis in the NP, as well as maintaining the AF structure. Moreover, ß-catenin loss-of-function decelerated the rapid induction of catabolic reactions in disc matrix and attenuated pain-related neural events during disc degeneration. Thus, our data demonstrate that targeting ß-catenin in disc cells through CRISPR-Cas9 has multifaceted therapeutic effects on disc degeneration, and we suggest that ß-catenin plays a fundamental role in the remodeling and degenerative processes of the disc. In addition, this study proposes that CRISPR-Cas9 is a useful tool for identifying new drug targets and developing therapeutic strategies for disc degeneration.

Platelet-Activating Biominerals Enhanced Injectable Hydrogels With Superior Bioactivity for Bone Regeneration.

Refractory bone fracture, which is difficult to be treated, is a common clinical disease. Taking inspiration from the natural process of bone regeneration, we provide a biomimetic strategy to develop a new injectable biomaterial for repairing bone defects, which is mainly composed of platelets, fibrins, and biominerals. Biomineral nanoparticles (EACPNs) with an amorphous phase are prepared by an enzyme-catalyzed route and display a platelet-activating property. The composite hydrogel (EPH) of EACPNs, fibrins, and platelets is injectable, and has similar chemical properties to natural materials in bone regeneration. The dried EPH samples display a highly porous structure, which would be favorable for cell attachment and growth. The results from in vitro studies indicate that EPH has high biocompatibility and superior bioactivity in promoting the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Furthermore, the results from in vivo studies clearly indicate that EPH can induce the formation of new collagen and vessels in the defect area, thus leading to faster regeneration of bone defects at 2 weeks. Our study provides a strategy for designing new biomimetic materials, which may be favorable in the treatment of refractory bone fracture.

Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration.

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO 4 3 - , when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

Original Designed Uniportal-Bichannel Spinal Endoscopic System (UBiSES) for Foraminoplasty in Percutaneous Endoscopic Transforaminal Discectomy.

OBJECTIVE: The study introduced uniportal-bichannel spinal endoscopic system (UBiSES) and explored the feasibility of applying UBiSES to conduct lumbar foraminoplasty in percutaneous endoscopic transforaminal discectomy (PETD). METHODS: This is a cohort study. 36 patients confirmed as L5/S1 lumbar disc herniation (LDH) in our hospital from March, 2019 to November, 2019 were enrolled. 36 patients were divided into two groups named the UBiSES group (n = 18, male: female = 8:10) and the TESSYS group (n = 18, male: female = 10:8). The average age of the UBiSES group and the TESSYS group were 40.94 ± 12.39 years old and 39.78 ± 13.02 years old respectively. PETD via uniportal-bichannel foraminoplasty assisted by UBiSES was adopted on the UBiSES group while PETD via conventional foraminoplasty was performed on the TESSYS group. One experienced surgeon with more than 4000 cases of lumbar surgery performed PETD on all patients. The demographic data, the duration of working cannula placement (minutes), decompression time (minutes), radiation exposure time (seconds), complications, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) scores and modified MacNab criteria were recorded and analyzed. The magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to evaluate the radiographic improvement. RESULTS: PETD via lumbar foraminoplasty was successfully performed in all cases. The follow-up points were 3 months, 6 months, and 12 months. The average follow-up period of all patients was 15.78 ± 2.29 months. There was no statistic difference in age (P = 0.81), sex (P = 0.51) and follow-up (P = 0.14) between two groups. The duration of working cannula placement was 19.08 ± 2.30 min in the UBiSES group and 24.90 ± 4.71 min in the TESSYS group and there was significant difference between two groups (P < 0.05). There was no statistic difference in decompression time between the UBiSES group (44.18 ± 5.70 min) and the TESSYS group (47.46 ± 5.96 min) (P = 1.70). The radiation exposure time was 28.00 ± 4.70 s in the UBiSES group and 40.50 ± 5.73 s in the TESSYS group respectively, and has significant difference between two groups (P < 0.05). Furthermore, there was significant different in the duration of working cannula placement and radiation exposure time in male or female between the UBiSES group and the TESSYS group (P < 0.05). For male or female, no difference observed in decompression time and follow-up period between two groups. Postoperative VAS of low back and leg at every follow-up point (1 day, 3 months, 6 months, 12 months) was improved significantly in both groups compared with their preoperative VAS (P < 0.05). The postoperative ODI (3 months, 6 months, 12 months) has decreased significantly in both the UBiSES group and the TESSYS group compared with their preoperative ODI (P < 0.05). 94.44% patients received an excellent or good recovery in the UBiSES group and 88.89% for the TESSYS group. There was no poor result reported in both groups. The radiographic images showed satisfactory foraminoplasty and sufficient decompression of nerve in both groups. No postoperative complications were observed during follow-ups in the UBiSES group. Two patients in the TESSYS group experienced postoperative dysesthesia and the symptom was disappeared in 5 days and 7 days respectively with dexamethasone and neurotrophic drugs treatment. CONCLUSIONS: The original designed UBiSES could effectively and safely enlarge the foramen with an extensive surgical view and space under full-time and real-time visualization and get satisfactory efficacy.

Dexamethasone-loaded thermo-sensitive hydrogel attenuates osteoarthritis by protecting cartilage and providing effective pain relief.

BACKGROUND: We utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)-dexamethasone-loaded thermo-sensitive hydrogel (DLTH). METHODS: The effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group, Model group and DLTH group. The DLTH group received joint injections of 10 µL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated. RESULTS: It took 20 minutes to form DLTH at pH 7.0 and 37 °C. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 °C revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded. CONCLUSIONS: Data presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.

The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability.

AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 in osteogenesis remains unknown. In this study, we report that ALKBH5 mRNA and protein expression were upregulated during osteoblast differentiation and that ALKBH5 knockdown suppressed osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. Conversely, ALKBH5 overexpression promoted osteogenesis. Moreover, the expression of wild-type ALKBH5, but not the m6A-modified active site mutant ALKBH5, could rescue ALKBH5 knockdown-induced osteogenesis inhibition. Furthermore, knockdown of ALKBH5 significantly impaired the mRNA stability of the transcription factor Runx2, which plays a key role in osteoblast differentiation. Taken together, our results suggest that ALKBH5 promotes osteogenesis through modulating Runx2 mRNA stability.

Upper Lumbar Intradural Disc Herniation: A Rare Case Report and Etiologic Analysis.

BACKGROUND: Intradural disc herniation (IDH) is a rare type of disc degeneration that infrequently affects the upper lumbar spine. Pre- and intraoperative diagnosis and surgical management of IDH are challenging. The present case study provides insight into these aspects of upper lumbar IDH and discusses possible mechanisms. CASE DESCRIPTION: A 63-year-old female with a history of chronic lower back and leg pain presented with an acute lumbar sprain that had occurred 1 month prior. The pain progressed and spread to the front of the left thigh, which affected her ability to lift her leg when ascending/descending stairs. Sagittal gadolinium-enhanced magnetic resonance imaging (MRI) revealed a disc protruding into the ventral dural sac showing a hawk-beak sign, and the posterior edge of the disc annulus and local posterior longitudinal ligament was broken. Total L2 laminectomy was performed, and the dorsal side of the dural sac was exposed and incised to enable exploration of the ventral side of the dura. We found two free fragments protruding into the inner wall of the dura through the left ventral dura mater defect. After carefully and completely removing the mass, we repaired the defect and performed internal fixation. Postoperative pathologic analysis confirmed that the mass was nucleus pulposus tissue from the degenerated disc. The patient's pain significantly improved after surgery, and she was able to walk normally at the 1-month follow-up. CONCLUSION: Upper lumbar IDH is an extremely rare type of disc degeneration. An enhanced MRI scan can provide diagnostic evidence, but the final diagnosis requires surgical exploration of the path of herniation and pathologic examination of the mass lesion.

Percutaneous Endoscopic Lumbar Discectomy via Transforaminal Approach Combined with Interlaminar Approach for L4/5 and L5/S1 Two-Level Disc Herniation.

OBJECTIVE: The purpose of the present study was to discuss a new surgical strategy that combines percutaneous endoscopic transforaminal discectomy (PETD) with percutaneous endoscopic interlaminar discectomy (PEID) for L4/5 and L5/S1 two-level disc herniation. METHODS: This was a retrospective study. A total of 19 patients with L4/5 and L5/S1 two-level lumbar disc herniation (LDH) who underwent percutaneous endoscopic lumbar discectomy (PELD) in our hospital from January 2015 to June 2016 were retrospectively examined. The average age of these 19 patients was 42.21 ± 14.88 years old, including 12 men and 7 women. One experienced surgeon who had carried out more than 3000 lumbar surgeries performed PELD for these patients. During the PELD surgery, the transforaminal approach was adopted for L4/5 level disc herniation and the interlaminar approach was adopted for L5/S1 level disc herniation. The demographic data, operation time (min), fluoroscopy times, hospital stay (days), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry disability index (ODI) scores, and the modified MacNab criteria were used to evaluate the surgical outcomes. MRI was conducted to evaluate the radiographic improvement. RESULTS: All patients underwent PELD via the transforaminal approach combined with the interlaminar approach successfully and achieved satisfactory efficacy. The follow-up points were 3, 12, and 18 months. The average hospital stay (days) and the average follow up (months) were 3.32 ± 0.98 and 18.63 ± 3.84, respectively. The operation time and fluoroscopy times were 85.79 ± 12.90 min and 39.05 ± 4.59 times, respectively. The fluoroscopy times (frequency) for L4/5 and L5/S1 were 26.95 ± 6.41 and 12.11 ± 3.49 (t = 7.00, P < 0.05). Furthermore, there was no significant difference for fluoroscopy times between male and female patients (t = 0.89, P = 0.99). The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 5.58 ± 2.01 and 2.37 ± 1.01, respectively (t = 7.14, P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 7.00 ± 1.56 and 1.63 ± 1.01, respectively (t = 20.97, P < 0.05). There were significant differences between preoperative VAS-Back and the last follow-up VAS-Back in men (t = 4.61, P < 0.05) and women (t = 6.57, P < 0.05). In addition, there was significant differences between preoperative VAS-Leg and the last follow-up VAS-Leg in men (t = 13.48, P < 0.05) and women (t = 26.87, P < 0.05). There were significant differences between preoperative ODI scores (44.84 ± 10.82%) and the last follow-up ODI scores (11.12 ± 5.80%) (t = 10.92, P < 0.05). Preoperative ODI scores and the last follow-up ODI scores were significantly different for men (t = 8.80, P < 0.05) and women (t = 6.63, P < 0.05). All patients received significant pain relief and functional improvement after the surgery. Except for two cases of postoperative dysesthesia and one dural tear, no severe complications occurred. The dysesthesia symptoms of these two patients disappeared within 1 week with the application of dexamethasone and neurotrophic drugs and the dural tear case also recovered well as the dural laceration was small. No poor results were reported and 89.47% of patients achieved excellent or good recovery. CONCLUSION: Percutaneous endoscopic lumbar discectomy via the transforaminal approach combined with the interlaminar approach under epidural anesthesia can treat L4/5 and L5/S1 two-level disc herniation safely and effectively.

LncRNA SNHG16 contributes to osteosarcoma progression by acting as a ceRNA of miR-1285-3p.

BACKGROUND: The long non-coding (lnc) RNA activated by small nucleolar RNA host gene 16 (SNHG16), which has been reported to play a vital role in a number of different types of cancer, is a novel lncRNA. However, following an osteosarcoma (OS) study, the expression pattern, biological roles, clinical values and potential molecular mechanism of SNHG16 remain unclear. In the current study, we aimed to examine its expression and possible function in osteosarcoma (OS). METHOD: Cell proliferation was measured by colony formation assay and Cell Counting Kit-8 (CCK-8) in vitro, and xenograft transplantation assay in vivo. Meanwhile, we used transwell chambers to test cell migration and invasion was evaluated. Cell cycle and apoptosis was evaluated by flow cytometry assay. Immunoblotting and qPCR analysis was carried out to detect protein and gene expression, respectively. Luciferase reporter assay was used to predict the potential downstream genes. RESULTS: The present study demonstrated that SNHG16 is highly expressed in both the tissues of patients with OS, as well as OS cell lines, and its expression level was positively correlated with clinical stage and poor overall survival. Functional assays revealed that the depletion of SNHG16 inhibits OS growth, OS cell progression and promotes apoptosis both in vivo and in vitro. In addition, the present study revealed that microRNA-1285-3p expression levels can be decreased by SNHG16 acting as a 'sponge', and that this pathway takes part in OS tumor growth in vivo, and OS cell proliferation, invasion, migration and apoptosis in vitro. CONCLUSIONS: The results from the present study demonstrate the role of lncRNA SNHG16 in OS progression, which is SNHG16 might exert oncogenic role in osteosarcoma (OS) by acting as a ceRNA of miR-1285-3p, and it may become a novel target in OS therapy.