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.

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.

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.

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.

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.

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.

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.

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.

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.

Percutaneous Endoscopic Lumbar Discectomy (PELD) via a Transforaminal and Interlaminar Combined Approach for Very Highly Migrated Lumbar Disc Herniation (LDH) Between L4/5 and L5/S1 Level.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has become one of the most popular minimally invasive surgeries for lumbar disc herniation (LDH), however, very highly migrated LDH is still a tricky issue for PELD. This study reported a new endoscopic discectomy strategy for the treatment of very highly migrated LDH between the L4/5 and L5/S1 level. MATERIAL AND METHODS The current study retrospectively analyzed 12 patients who accepted PELD for very highly migrated LDH between the L4/5 and L5/S1 level. Under local anesthesia, the transforaminal approach was chosen for the L4/5 level and the interlaminar approach was chosen for the L5/S1 level. The 10-point visual analogue scale (VAS) was used to assess back pain (VAS-Back) and leg pain (VAS-Leg). Oswestry disability index (ODI) and Modified Mac Nab Criteria were adopted as the functional evaluation methods. All patients were followed in the outpatient department for at least 12 months after their operation. RESULTS Our study showed that very highly migrated disc between L4/5 and L5/S1 level could be removed completely by this strategy. Except for 1 case of postoperative dysesthesia and 1 case of dural tear, no severe complication occurred. At the last follow-up, the average VAS-Back score of the study patients was reduced from 5.17±2.12 to 2.08±1.08 (P<0.05) and the average VAS-Leg score was reduced from 7.25±1.48 to 1.33±0.89 (P<0.05). The average ODI scores improved from 48.50±10.59 to 13.00±2.76 (P<0.05). According to the Modified Mac Nab Criteria, 83.33% of patients (10 out of 12 patients) received an excellent or good recovery and no poor result was reported. No recurrence was observed during follow up. CONCLUSIONS PELD via a transforaminal and interlaminar combined approach provides an alternative option for select patients with very highly migrated LDH between the L4/5 and L5/S1 level.

Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis.

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA-Seq and quantitative PCR to characterize disc degeneration-associated miRNAs. We identified three miRNAs, including miR-26a-5p, miR-122-5p and miR-215-5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR-26a-5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre-injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR-122-5p and miR-215-5p exhibited lower expression in post-injury samples than in their counterparts without the surgery. Moreover, we found that miR-26a-5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR-26a-5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR-26a-5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.

The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression.

Osteoarthritis (OA) is a common, painful disease. Currently OA is incurable, and its etiology largely unknown, partly due to limited understanding of OA as a whole-joint disease. Here we report that two homologous microRNAs, miR-204 and miR-211, maintain joint homeostasis to suppress OA pathogenesis. Specific knockout of miR-204/-211 in mesenchymal progenitor cells (MPCs) results in Runx2 accumulation in multi-type joint cells, causing whole-joint degeneration. Specifically, miR-204/-211 loss-of-function induces matrix-degrading proteases in articular chondrocytes and synoviocytes, stimulating articular cartilage destruction. Moreover, miR-204/-211 ablation enhances NGF expression in a Runx2-dependent manner, and thus hyper-activates Akt signaling and MPC proliferation, underlying multiplex non-cartilaginous OA conditions including synovial hyperplasia, osteophyte outgrowth and subchondral sclerosis. Importantly, miR-204/-211-deficiency-induced OA is largely rescued by Runx2 insufficiency, confirming the miR-204/-211-Runx2 axis. Further, intraarticular administration of miR-204-expressing adeno-associated virus significantly decelerates OA progression. Collectively, miR-204/-211 are essential in maintaining healthy homeostasis of mesenchymal joint cells to counteract OA pathogenesis.

Exploration of CRISPR/Cas9-based gene editing as therapy for osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a painful and debilitating disease and it is associated with aberrant upregulation of multiple factors, including matrix metalloproteinase 13 (MMP13), interleukin-1ß (IL-1ß) and nerve growth factor (NGF). In this study, we aimed to use the CRISPR/Cas9 technology, a highly efficient gene-editing tool, to study whether the ablation of OA-associated genes has OA-modifying effects. METHODS: We performed intra-articular injection of adeno-associated virus, which expressed CRISPR/Cas9 components to target each of the genes encoding MMP13, IL-1ß and NGF, in a surgically induced OA mouse model. We also tested triple ablations of NGF, MMP13 and IL-1ß. RESULTS: Loss-of-function of NGF palliates pain but worsens joint damage in the surgically induced OA model. Ablation of MMP13 or IL-1ß reduces the expression of cartilage-degrading enzymes and attenuates structural deterioration. Targeting both MMP13 and IL-1ß significantly mitigates the adverse effects of NGF blockade on the joints. CONCLUSIONS: CRISPR-mediated ablation of NGF alleviates OA pain, and deletion of MMP13-1ß or IL-1ß attenuates structural damage in a post-traumatic OA model. Multiplex ablations of NGF, MMP13 and IL-1ß provide benefits on both pain management and joint structure maintenance. Our results suggest that CRISPR-based gene editing is useful for the identification of promising drug targets and the development of feasible therapeutic strategies for OA treatment.

Runx2 is required for postnatal intervertebral disc tissue growth and development.

Runx2 plays an essential role in embryonic disc tissue development in mice. However, the role of runt-related transcription factor 2 (Runx2) in postnatal disc tissue growth and development has not been defined. In the present studies, we generated Runx2 conditional knockout (KO) mice (Runx2Agc1ER ), in which Runx2 was deleted in Aggrecan-expressing cells in disc tissue at postnatal 2-weeks of age. We then analyzed changes in disc tissue growth and development using histology and immunohistochemical methods in 3-month-old mice. We found that large vacuolated notochordal cells were accumulated in the nucleus pulposus (NP) in Runx2 KO mice. The growth plate cartilage tissue in the disc was thicker in Runx2 KO mice. We also found a significant upregulation of Indian hedgehog (Ihh) expression in the cells in NP cells and in annulus fibrosus cells of Runx2 KO mice. These results demonstrated that Runx2 may play an important role in postnatal disc tissue development through interacting with Ihh signaling.

Concentric Stereotactic Technique of Percutaneous Endoscopic Transforaminal Discectomy and Radiation Exposure to Surgeons.

OBJECTIVE: In percutaneous endoscopic transforaminal discectomy (PETD), surgeons are exposed to intraoperative radiographic radiation over a long-term career, which may be correlated with high risk of iatrogenic radiation hazards. The purpose of this prospective cohort study was to assess the impact of concentric stereotactic technique on radiation exposure to surgeons in PETD. METHODS: Patients who underwent conventional PETD were regarded as group A, whereas those undergoing PETD with concentric stereotactic technique were considered as group B. The primary outcomes were cumulative radiation dose to the surgeon's eye, thyroid gland, and breast. RESULTS: A total of 34 patients were treated in group A and 30 patients were treated in group B. The cumulative radiation dose of the eye per operation was 0.017 (0.58/34) mSv in group A and 0.010 (0.31/30) mSv in group B, which meant a reduction of 41.18%. The cumulative radiation dose of the thyroid gland per operation was 0.018 (0.60/34) mSv in group A and 0.011 (0.33/30) mSv in group B, which meant a reduction of 38.89%. The cumulative radiation dose of the chest per operation was 0.039 (1.33/34) mSv in group A and 0.023 (0.70/30) mSv in group B, which meant a reduction of 41.03%. There were no significant differences in hospital stay, visual analog scale score of waist and leg pain, Oswestry Disability Index score, MacNab satisfaction, and complications between the 2 groups (P > 0.05). CONCLUSIONS: The concentric stereotactic technique can effectively reduce radiation exposure to surgeons by about 40%.

Comparison of 3 Anesthetic Methods for Percutaneous Transforaminal Endoscopic Discectomy: A Prospective Study.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) under local anesthesia (LA) is growing popular in recent years because of its safety, effectiveness and increased patient demands for minimally invasive procedures. To avoid neural injuries, local anesthesia that can keep the patient conscious is recommended. However, many patients complain about the severe pain during surgery. Epidural anesthesia (EA) is an alternative choice. We put forward an anesthetic method that combined preemptive analgesia (PA) and local anesthesia. OBJECTIVES: The study aimed to assess the effectiveness of 3 methods of anesthesia for PTED, LA, EA and PA. STUDY DESIGN: A prospective study. METHODS: Three groups of patients were treated with standard PTED under LA, PA or EA, respectively. The data collected for analysis were operative time, x-ray exposure time, postoperative bed time, visual analog scale (VAS), Oswestry Back Pain Disability Index (ODI), the global outcome based on the Macnab outcome criteria, satisfaction rate of anesthesia, and complications. RESULTS: A total of 240 consecutive patients were enrolled in this study from January 2014 to December 2016. Among 3 groups, 1-week postoperatively VAS (back and leg) and ODI were improved compared with preoperative data, and the excellent/good rates were all above 90%. However, satisfaction rate of anesthesia showed significant differences among the 3 groups. PA and EA showed significantly better performance in pain management intraoperatively and 1 hour postoperatively. The operation time of group PA was the shortest and group EA was the longest. No severe neural injuries occurred in any of the 3 groups. Transient paresis of lower limbs occurred in all 3 groups and showed no significant differences. Decreased muscle strength of lower limbs postoperatively occurred in 2 patients in group EA. The incidence of nausea and vomiting postoperatively was significantly higher in group PA (6 cases, 7.50%). There were 3 cases of dysuria postoperatively in group EA (3.75%). LIMITATION: First, this is a single center study. Second, this study investigated the effects of anesthesia on perioperative period and the follow-up time was relatively short. Third, we choose morphine in group PA and there are other types of anesthetics which may be used in preemptive analgesia in further study. CONCLUSION: All 3 of these anesthetic methods are safe to avoid neural injuries. EA and PA showed better performance in pain management but had more anesthesia-related complications. KEY WORDS: Percutaneous transforaminal endoscopic discectomy (PTED), local anesthesia, epidural anesthesia, preemptive analgesia, morphine, ropivacaine, pain management, visual analog scale (VAS), Oswestry Back Pain Disability Index (ODI).