Leptin attenuates the osteogenic induction potential of BMP9 by increasing ß-catenin malonylation modification via Sirt5 down-regulation.

BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found Leptin was decreased during BMP9-induced osteogenic differentiation and serum Leptin concentrations were increased in the ovariectomized (OVX) rats. Both in vitro and in vivo, exogenous expression of Leptin inhibited the process of osteogenic differentiation, whereas silencing Leptin enhanced. Exogenous Leptin could increase the malonylation of ß-catenin. However, BMP9 could increase the level of Sirt5 and subsequently decrease the malonylation of ß-catenin; the BMP9-induced osteogenic differentiation was inhibited by silencing Sirt5. These data suggested that Leptin can inhibit the BMP9-induced osteogenic differentiation, which may be mediated through reducing the activity of Wnt/ß-catenin signalling via down-regulating Sirt5 to increase the malonylation level of ß-catenin partly.

Unilateral Biplanar Screw-Rod Fixation Technique for the Treatment of Odontoid Fractures in Patients with Atlantoaxial Bone or Vascular Abnormalities.

OBJETIVE: This study aims to introduce the unilateral biplanar screw-rod fixation (UBSF) technique (a hybrid fixation technique: 2 sets of atlantoaxial screws were placed on the same side), which serves as a salvage method for traditional posterior atlantoaxial fixation. To summarize the indications of this technique and to assess its safety, feasibility, and clinical effectiveness in the treatment of odontoid fractures. METHODS: Patients with odontoid fractures were enrolled according to special criteria. Surgical duration and intraoperative blood loss were documented. Patients were followed up for a minimum of 12 months. X-ray and computerized tomography scans were conducted and reviewed at 1 day, and patients were asked to return for computerized tomography reviews at 3, 6, 9, and 12 months after surgery until fracture union. Recorded and compared the Neck Visual Analog Scale and Neck Disability Index presurgery and at 1 week and 12 months postsurgery. RESULTS: Between January 2016 and December 2022, our study enrolled 7 patients who were diagnosed with odontoid fractures accompanied by atlantoaxial bone or vascular abnormalities. All 7 patients underwent successful UBSF surgery, and no neurovascular injuries were recorded during surgery. Fracture union was observed in all patients, and the Neck Visual Analog Scale and Neck Disability Index scores improved significantly at 1 week and 12 months postoperative (P < 0.01). CONCLUSIONS: The UBSF technique has been demonstrated to be safe, feasible, and effective in treating odontoid fractures. In cases where the atlantoaxial bone or vascular structure exhibits abnormalities, it can function as a supplementary or alternative approach to the conventional posterior C1-2 fixation.

The anatomic study and surgical technique for canal decompression with "pedicle-plasty" strategy in lumbar burst fractures with pedicle rupture.

In the treatment of lumbar burst fractures with nerve injury, fusion is often required to rebuild spinal stability, but it can lead to the loss of motor units and increase the occurrence of adjacent segment diseases. Thus, a novel approach of lumbar canal decompression with "pedicle-plasty" strategy (DDP) was needed in clincal treatment. Firstly, image measurement analysis, the images of 60 patients with lumbar spine CT examinations were selected to measure osteotomy angle (OA), distance from the intersection of osteotomy plane and skin to the posterior midline (DM),transverse length of the osteotomy plane (TLOP), and sagittal diameter of the outer edge of superior articular process (SD). Secondary, cadaver study, distance between the intermuscular space and midline (DMSM), anterior and posterior diameters of the decompression (APDD), and lateral traction distance of the lumbosacral plexus (TDLP) were measured on 10 cadaveric specimens. Finally, procedure of DDP was demonstrated on cadaver specimens. OA ranged from 27.68°+4.59° to 38.34°+5.97°, DM ranged from 43.44+6.29 to 68.33+12.06 mm, TLOP ranged from 16.84+2.19 to 19.64+2.36 mm, and SD ranged from 22.49+1.74 to 25.53+2.21 mm. DMSM ranged from 45.53+5.73 to 65.46+6.43 mm. APDD were between 10.51+3.59 and 12.12+4.54 mm, and TDLP were between 3.28+0.81 and 6.27+0.62 mm.DDP was successfully performed on cadaveric specimens. DDP, as a novel approach of decompression of burst fractures with pedicle rupture, can fully relieve the occupation and at the same time preserve the spinal motor unit because of no resection of intervertebral discs and no destruction of facet joints,and has certain developmental significance.

Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.

DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

The SIRT1 activator SRT2104 promotes BMP9-induced osteogenic and angiogenic differentiation in mesenchymal stem cells.

Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways.

Cardiac CIP protein regulates dystrophic cardiomyopathy.

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model.

BACKGROUND: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)-enhanced bone marrow-derived mesenchymal stem cells (BMSCs) for cartilage regeneration. PURPOSE: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. STUDY DESIGN: Controlled laboratory study. METHODS: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π-π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN-preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. RESULTS: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN-preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. CONCLUSION: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. CLINICAL RELEVANCE: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

Erratum to: Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

[Erratum to: BMB Reports 2012; 45(9): 509-514, PMID: 23010171] The BMB Reports would like to correct in the Figure 2 of BMB Rep. 2012; 45(9): 509-514 titled "Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells." The original version of this article unfortunately contained image assembling error in the Figure 2. The image for "GFP-Day13" group was inadvertently duplicated from that for "BT20-Day 5" group, and an incorrect image was used for "GFP-Day 17" group. This article has been updated to correct this error in Figure 2.

The role of Serpina3n in the reversal effect of ATRA on dexamethasone-inhibited osteogenic differentiation in mesenchymal stem cells.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA). METHODS: Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein-DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis. RESULTS: ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARß) was elevated. RARß inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARß can regulate the expression of Serpina3n. CONCLUSION: ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.

Long non-coding RNA (LncRNA) HOTAIR regulates BMP9-induced osteogenic differentiation by targeting the proliferation of mesenchymal stem cells (MSCs).

Long non-coding RNAs are important regulators of biological processes, but their roles in the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. Here we investigated the role of murine HOX transcript antisense RNA (mHotair) in BMP9-induced osteogenic differentiation of MSCs using immortalized mouse adipose-derived cells (iMADs). Touchdown quantitative polymerase chain reaction analysis found increased mHotair expression in bones in comparison with most other tissues. Moreover, the level of mHotair in femurs peaked at the age of week-4, a period of fast skeleton development. BMP9 could induce earlier peak expression of mHotair during in vitro iMAD osteogenesis. Silencing mHotair diminished BMP9-induced ALP activity, matrix mineralization, and expression of osteogenic, chondrogenic and adipogenic markers. Cell implantation experiments further confirmed that knockdown of mHotair attenuated BMP9-induced ectopic bone formation and mineralization of iMADs, leading to more undifferentiated cells. Crystal violet staining and cell cycle analysis revealed that silencing of mHotair promoted the proliferation of iMAD cells regardless of BMP9 induction. Moreover, ectopic bone masses developed from mHotair-knockdown iMAD cells exhibited higher expression of PCNA than the control group. Taken together, our results demonstrated that murine mHotair is an important regulator of BMP9-induced MSC osteogenesis by targeting cell cycle and proliferation.

Posterior Percutaneous Transpedicular Endoscopic Approach for Treating Single-Segment Cervical Myelopathy.

BACKGROUND: Standard posterior percutaneous endoscopic cervical discectomy (PECD) is considered an effective minimally invasive surgery. Although standard PECD can be used to treat radiculopathy with relatively minimal trauma, it is still a challenge to use this approach for treating myelopathy. OBJECTIVE: This report is aimed at first describing a posterior transpedicular approach under endoscopy for myelopathy and evaluating the feasibility and short-term clinical effects of this approach. METHODS: In our retrospective analysis between Feb. 2016 to Mar. 2017, 16 patients managed with PECD using the posterior transpedicular approach for symptomatic single-segment myelopathy. Surgery involved drilling 1/2 to 2/3 of the medial portion of the pedicle under endoscopy to provide sufficient space and an appropriate angle for inserting the endoscope into the spinal canal, followed by ventral decompression of the spinal cord. Computed tomography and magnetic resonance imaging were used to evaluate pedicle healing and spinal cord decompression. The primary outcomes included a visual analog scale (VAS) scores of axial neck pain and Japanese Orthopaedic Association (JOA) scores of neurological conditions. RESULTS: All patients completed a 1-year follow-up examination. The mean duration of surgery was 95.44 ± 19.44 min (52-130 min). The fluoroscopy duration was 5.88 ± 1.05 (4-7). The VAS scores of axial pain significantly improved from 6.94 ± 0.75 preoperatively to 2.88 ± 1.22 postoperatively (P < 0.05). The mean JOA scores improved from 8.50 ± 1.12 preoperatively to 14.50 ± 1.46 at the final follow-up (P < 0.05). The effects were excellent in 8 cases, good in 6 cases, and fair in 2 cases. After partial pedicle excision, the width of the remaining pedicle was 1.70 ± 0.22 mm postoperatively and significantly recovered to 3.38 ± 0.49 mm at the 1-year follow-up. There were no surgery-related complications, such as dural tearing, spinal cord injury, nerve root injury, pedicle fracture, and cervical hematocele or infection. CONCLUSIONS: The posterior transpedicular approach is an effective method for the treatment of myelopathy in select patients and is a supplement to the described surgical approach for PECD.

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Niclosamide: drug repurposing for human chondrosarcoma treatment via the caspase-dependent mitochondrial apoptotic pathway.

Poor sensitivity to chemotherapy drugs and high recurrence rates are the bottlenecks to successful chondrosarcoma treatment. Notably, niclosamide has been identified as a potential anti-cancer agent. To investigate the effects and mechanisms of niclosamide in the context of human chondrosarcoma treatment, SW1353 and CAL78 human chondrosarcoma cells were treated with various concentrations of niclosamide. The CKK-8 assay was performed to quantify cell viability. Cell proliferation was determined with crystal violet staining and colony forming assays. TUNEL and annexin V-FITC flow cytometry assays were performed to detect cell apoptosis. Wound healing and Transwell assays were conducted to evaluate migratory and invasive cell behaviors. The effect of niclosamide on the mitochondria was evaluated with the JC-1 and Seahorse Cell Mito Stress Assays. The expression of caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and ß-tubulin levels were investigated by western blotting. Collectively, the data demonstrated that niclosamide inhibited cell growth and proliferation, attenuated migratory and invasive cell behaviors, and promoted apoptosis. Niclosamide is as a potent chondrosarcoma tumor inhibitor that activates the caspase-dependent mitochondrial apoptotic pathway and could be a novel therapeutic approach to treat chondrosarcoma.

Can the Novel LumboIliac Triangle Technique Based on Biplane Oblique Fluoroscopy Facilitate Transforaminal Percutaneous Endoscopic Lumbar Discectomy for Patients with L5-S1 Disc Herniation Combined with High Iliac Crest? Case-Control Study of 100 Patients.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) via the transforaminal approach is difficult at L5-S1 in patients presenting with high iliac crests (HIC). The conventional wisdom is that measurement using lumbar radiography, computed tomography (CT), or magnetic resonance imaging (MRI) is necessary. OBJECTIVES: The objective of this study was to introduce a lumbo-iliac triangular (LI-Tri) technique based on biplane oblique fluoroscopy and verify whether it facilitated transforaminal PELD for patients with L5-S1 lumbar disc herniation (LDH) combined with HIC. STUDY DESIGN: A retrospective analysis. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: One hundred patients with L5-S1 LDH combined with HIC were treated with PELD. The LI-Tri technique was used in the first 50 patients (applied group). The other 50 patients were classified as the nonapplied group, in which the conventional technique was performed. Clinical outcome evaluation included Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) scores. The intervals of follow-up were scheduled at 1 day and 1, 3, 6, 12, and 24 months postoperatively. RESULTS: No significant difference was observed with respect to demographic information (P < .05, respectively). There were 8 patients in the nonapplied group with difficult punctures. Together with the remaining 50 patients, the puncture was successful with the LI-Tri technique. The mean operative duration was shorter in the applied group (55 vs 70 min, P < .01). Compared to the preoperative data, only the back pain VAS and ODI in the nonapplied group were nonsignificantly lower at one day postoperatively (P > .05, respectively). With the exception of the back pain VAS and ODI at one day postoperatively, no significant differences were observed in the 3 parameters at other time points postoperatively between 2 groups (P > .05, respectively). LIMITATIONS: The study is limited by its retrospective, nonrandomized controlled design. CONCLUSIONS: For patients with L5-S1 LDH combined with HIC treated by transforaminal PELD, the LI-Tri technique is simple and effective in preoperative evaluations, locating the skin entry point and guiding the puncture trajectory. Compared to the conventional technique, it shows advantages in terms of reducing intraoperative surgical duration and promoting fast postoperative recovery. KEY WORDS: Endoscopic discectomy, iliac crest, L5-S1 disc, PELD, percutaneous, transforaminal.

The combinations of multiple factors to improve the diagnostic sensitivity and specificity after artificial joint infection.

OBJECTIVE: To discuss the sensitivity and specificity of the combinations of multiple factors that work on bone infection after artificial joint, and provide evidence-based medical basis for the early diagnosis of infection after artificial joint. METHODS: A retrospective review was conducted on 35 patients diagnosed with periprosthetic joint infections (PJI) or aseptic loosening (AL) who both received revision operation from January 2011 to January 2015. Analyzing and comparing their epidemiology indexes and expounded a series of auxiliary examinations corresponding positive diagnosis ratio. RESULTS: Thirty-five patients were divided into two groups. One is called group PJI which includes 16 patients, and the other is called group AL which contains 19 patients. There was no statistical difference between in age (p = 0.536), gender ratio (p = 0.094), and the time of catching infection or getting loose (p = 0.055). Swelling was statistical significant (p = 0.0435 < 0.05). AUC of CRP = 0.947, ESR = 0.893, IL-6 = 0.893, PCT = 0.781, WBC = 0.839, and PMN = 0.755, respectively, CRP has a high diagnostic value to PJI, ESR, IL-6, PCT, WBC, and PMN% possess a moderate diagnostic value. There were 3 cases of PJI whose pathological paraffin section showed infectious inflammatory cells (100%). three PJI patients and one AL patient whose 99mTc-MDP examination presented 100% infection or looseness rate. CONCLUSION: CRP has a high diagnostic value to PJI. Histopathology HE staining, Gram staining, and 99mTc-MDP provide a highly accurate diagnosis for PJI. Therefore, the results suggest combining the unique clinical symptoms of PJI patients with relevant laboratory indexes, histopathologic characteristics, and imageological examinations that can improve diagnostic sensitivity and specificity of PJI in its early stage.

Endoscopically-Assisted Percutaneous Unilateral Atlantoaxial Screw-Rod Nonfusion Fixation Treatment for Type II Odontoid Fractures in Geriatric Patients: Case Series and Technical Note.

BACKGROUND: Considerable controversy exists regarding the optimal treatment for type II odontoid fractures in geriatric patients. Surgical intervention can help patients return to their prior level of function as rapidly as possible while avoiding the morbidity and mortality associated with prolonged and bedbound hospitalization. However, the optimal treatment is still a difficult choice for patients with increased risk from anesthesia. OBJECTIVES: The objective of our study was to describe an innovative method of endoscopically-assisted percutaneous unilateral C1 lateral mass screw and C2 pedicle screw-rod nonfusion fixation for type II odontoid fractures in geriatric patients. STUDY DESIGN: A case series design and technical notes. SETTING: This study took place at Second Affiliated Hospital of Chongqing Medical University. METHODS: Seven geriatric patients (> 65 years) with type II odontoid fractures and an American Society of Anesthesiologists (ASA) score of 2 or higher received endoscopically-assisted percutaneous unilateral atlantoaxial screw-rod nonfusion fixation. After surgery, all patients were required to wear a rigid collar full-time for 12 weeks. Intraoperative data, the bone union time, American Spinal Injury Association (ASIA) scale scores, Neck Disability Index (NDI) scores, and postoperative complications were collected for assessment.RESULTS The surgical goal was successfully achieved in all patients, 3 of whom had high ASA scores (>= 3) and underwent surgery under local anesthesia. The operative time ranged from 112 to 169 minutes (mean, 131.1 minutes). No neurovascular complications were observed intraoperatively or postoperatively. All patients rapidly returned to their prior level of function and were followed up for 12 to 24 months (average: 16.9 months). Bone union was achieved in all patients. LIMITATIONS: This study is limited by being a retrospective study. CONCLUSIONS: Endoscopically-assisted percutaneous unilateral atlantoaxial screw-rod nonfusion fixation is a feasible technique for type II odontoid fractures in geriatric patients. This method offers a compromise between non-operative and operative treatment and allows geriatric patients to rapidly return to their prior level of function. KEY WORDS: Endoscopically-assisted surgery; geriatric patient; percutaneous atlantoaxial fixation; type II odontoid fracture; unilateral nonfusion fixation.

LSD1 negatively regulates autophagy in myoblast cells by driving PTEN degradation.

Lysine-specific demethylase 1 (LSD1) is a well characterized transcriptional regulator functioning on the chromatin to remove mono- and di-methyl groups from lysine 4 or lysine 9 of histone 3 (H3K4 or H3K9). LSD1 also has non-transcriptional activities via targeting non-histone substrates that participate in diverse biological processes. In this report, we determined that LSD1 negatively regulates autophagy in skeletal muscle cells by promoting PTEN degradation in a transcription-independent mechanism. In C2C12 cells, LSD1 inhibition or depletion significantly induced the initiation of autophagy; and autophagy resulted from LSD1 inhibition is associated with AKT/mTORC1 inactivation. Notably, the proteins of PTEN, a prominent repressive AKT modulator, are stabilized by LSD1 inhibition despite a decrease of its mRNA levels. Further data demonstrated that LSD1 interacts with PTEN protein and enhances its ubiquitination and degradation. Together, our findings identify a novel biological function of LSD1 in autophagy, mediated by regulating the stability of PTEN and the activity of AKT/mTORC1.

Modified K-Hole Percutaneous Endoscopic Surgery for Cervical Foraminal Stenosis: Partial Pediculectomy Approach.

BACKGROUND: Percutaneous endoscopic cervical discectomy has evolved as an efficient, minimally invasive spine surgery for radiculopathy caused by soft and/or osseous foraminal stenosis. Although interlaminar access can be used to resect lateral herniated lesions or osteophytes located in the foramina, with limited operative space, nerve retraction may be unavoidable. This procedure may injure the nerve root and cause postoperative arm pain, numbness, and muscle weakness, especially when the herniation is located in the ventral nerve root or when there is a massive osteophyte in the foramina. However, posterior partial cervical pediculectomy under endoscopy provides a new approach to effectively reduce or even avoid nerve retraction and reduce the potential risk of nerve injury. OBJECTIVES: This report presents a partial pediculectomy approach and compares the clinical outcomes of different surgical methods, including posterior percutaneous endoscopic cervical discectomy (P-PECD) and P-PECD combined with partial pediculectomySTUDY DESIGN: This study used a retrospective comparative study design. SETTING: This study took place at the Second Affiliated Hospital of Chongqing Medical University. METHODS: From February 2015 to March 2017, 84 patients with single-level and unilateral soft and/or osseous cervical foraminal stenosis were recruited. Patients were treated with P-PECD (40 patients) and P-PECD combined with partial pediculectomy (44 patients). Postoperative clinical outcomes were assessed using the modified MacNab grading criteria and the Visual Analog Scale (VAS) at different times after surgery. The surgery duration, dosage of postoperative analgesic medication, duration of hospital stay, and postoperative complications were recorded. RESULTS: The mean duration of the conventional P-PECD surgery was 74.48 ± 7.08 minutes, which was significantly longer (P = 0.002) than that observed for the P-PECD with partial pediculectomy (66.00 ± 9.62 minutes). The analgesic dosage in the conventional P-PECD group was significantly higher than that in the partial pediculectomy group (9.14 ± 3.07 units vs. 5.71 ± 3.41 units; P = 0.001). The hospital stay in the conventional P-PECD group was significantly longer than that in the partial pediculectomy group (3.86 ± 0.85 days vs. 3.24 ± 0.83 days; P = 0.022). The VAS scores at 1 day, 3 days, and 7 days after surgery in the conventional P-PECD group were significantly higher than those in the partial pediculectomy group (all P < 0.001). The modified MacNab grading criteria showed no significant difference at each follow-up (P = 1). The incidence of complications in the P-PECD with partial pediculectomy group (2/44, 4.55%) was significantly lower than that in the conventional P-PECD group (4/40, 10.0%), including complications of increased pain, increased numbness, and worsening of muscle weakness. LIMITATIONS: This study is limited by being a retrospective study, and by having a small sample size and a short follow-up period. CONCLUSIONS: As an alternative to the P-PECD surgical technique, P-PECD with partial pediculectomy effectively reduced the postoperative complications and may be preferable when considering the surgery duration, postoperative hospital stay, analgesic dosage, and postoperative VAS score. KEY WORDS: Cervical disc herniation, foraminal stenosis, percutaneous endoscopic cervical discectomy, PECD, P-PECD, partial pediculectomy.