Anti-osteoporosis activity of casticin in ovariectomized rats.

Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored. Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators. Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro. Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.

Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation.

Annulus fibrosus (AF) defect is an important cause of disc re-herniation after discectomy. The self-regeneration ability of the AF is limited, and AF repair is always hindered by the inflammatory microenvironment after injury. Hydrogels represent one of the most promising materials for AF tissue engineering strategies. However, currently available commercial hydrogels cannot withstand the harsh mechanical load within intervertebral disc. In the present study, an innovative triple cross-linked oxidized hyaluronic acid (OHA)-dopamine (DA)- polyacrylamide (PAM) composite hydrogel, modified with collagen mimetic peptide (CMP) and supplied with transforming growth factor beta 1 (TGF-ß1) (OHA-DA-PAM/CMP/TGF-ß1 hydrogel) was developed for AF regeneration. The hydrogel exhibited robust mechanical strength, strong bioadhesion, and significant self-healing capabilities. Modified with collagen mimetic peptide, the hydrogel exhibited extracellular-matrix-mimicking properties and sustained the AF cell phenotype. The sustained release of TGF-ß1 from the hydrogel was pivotal in recruiting AF cells and promoting extracellular matrix production. Furthermore, the composite hydrogel attenuated LPS-induced inflammatory response and promote ECM synthesis in AF cells via suppressing NFκB/NLRP3 pathway. In vivo, the composite hydrogel successfully sealed AF defects and alleviated intervertebral disk degeneration in a rat tail AF defect model. Histological evaluation showed that the hydrogel integrated well with host tissue and facilitated AF repair. The strategy of recruiting endogenous cells and providing an extracellular-matrix-mimicking and anti-inflammatory microenvironment using the mechanically tough composite OHA-DA-PAM/CMP/TGF-ß1 hydrogel may be applicable for AF defect repair in the clinic. STATEMENT OF SIGNIFICANCE: Annulus fibrosus (AF) repair is challenging due to its limited self-regenerative capacity and post-injury inflammation. In this study, a mechanically tough and highly bioadhesive triple cross-linked composite hydrogel, modified with collagen mimetic peptide (CMP) and supplemented with transforming growth factor beta 1 (TGF-ß1), was developed to facilitate AF regeneration. The sustained release of TGF-ß1 enhanced AF cell recruitment, while both TGF-ß1 and CMP could modulate the microenvironment to promote AF cell proliferation and ECM synthesis. In vivo, this composite hydrogel effectively promoted the AF repair and mitigated the intervertebral disc degeneration. This research indicates the clinical potential of the OHA-DA-PAM/CMP/TGF-ß1 composite hydrogel for repairing AF defects.

Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR-124/CILP/TGF-ß.

Immuno-inflammation is highly associated with anabolic and catabolic dysregulation of the extracellular matrix (ECM) in the nucleus pulposus (NP), which dramatically propels intervertebral disc degeneration (IVDD). With the characteristics of tissue remodeling and regeneration, M2c macrophages have attracted great attention in research on immune modulation that rebuilds degenerated tissues. Therefore, we first demonstrated the facilitating effects of M2c macrophages on ECM anabolism of the NP in vitro. We subsequently found that exosomes from M2c macrophages (M2c-Exoss) mediated their metabolic rebalancing effects on the ECM. To determine whether M2c-Exoss served as positive agents protecting the ECM in IVDD, we constructed an M2c-Exos-loaded hyaluronic acid hydrogel (M2c-Exos@HA hydrogel) and implanted it into the degenerated caudal disc of rats. The results of MRI and histological staining indicated that the M2c-Exos@HA hydrogel alleviated IVDD in vivo in the long term. To elucidate the underlying molecular mechanism, we performed 4D label-free proteomics to screen dysregulated proteins in NPs treated with M2c-Exoss. Cartilage intermediate layer protein (CILP) was the key protein responsible for the rebalancing effects of M2c-Exoss on ECM metabolism in the NP. With prediction and verification using luciferase assays and rescue experiments, miR-124-3p was identified as the upstream regulator in M2c-Exoss that regulated CILP and consequently enhanced the activity of the TGF-ß/smad3 pathway. In conclusion, we demonstrated ameliorating effects of M2c-Exoss on the imbalance of ECM metabolism in IVDD via the miR-124/CILP/TGF-ß regulatory axis, which provides a promising theoretical basis for the application of M2c macrophages and their exosomes in the treatment of IVDD.

Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway.

OBJECTIVE: Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. METHOD: ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. RESULT: The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. CONCLUSION: Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis.

Tuberculosis (TB) is a major infectious disease induced by Mycobacterium tuberculosis (M. tb) which causes the world's dominant fatal bacterial contagious disease. Increasing studies have indicated that exosomes may be a novel option for the diagnosis and treatment of TB. Exosomes are nanovesicles (30-150 nm) containing lipids, proteins and non-coding RNAs (ncRNAs) released from various cells, and can transfer their cargos and communicate between cells. Furthermore, exosomal ncRNAs exhibit diagnosis potential in bacterial infections, including TB. Additionally, differential exosomal ncRNAs regulate the physiological and pathological functions of M. tb-infected cells and act as diagnostic markers for TB. This current review explored the potential biological roles and the diagnostic application prospects of exosomal ncRNAs, and included recent information on their pathogenic and therapeutic functions in TB.

The Value of Multimodal Ultrasonic Scoring System in the Diagnosis of Carotid Vulnerable Plaque: A Comparative Study With Pathology.

BACKGROUND AND AIMS: Vulnerable plaques are closely related to ischemic stroke. To investigate the diagnostic value of multimodal plaque vulnerability ultrasound scoring system (PV-USS) using histopathology as the gold standard. METHODS: A total of 45 subjects who would be underwent carotid endarterectomy were recruited. The postoperative specimens were examined by histopathology. All responsible plaques were scanned dynamically in multiple sections by carotid ultrasound to measure maximum thickness and lumen stenotic degree, as well as, the echo, homogeneity, surface morphology, and echo type were observed. The above two-dimensional (2D) ultrasonic features were systematically scored, that is, PV-USS2D . Combined with contrast-enhanced ultrasonography (CEUS), neovascularization grade in plaque was scored, which is PV-USS2D+CEUS . RESULTS: According to the pathological results, 45 subjects were divided into vulnerable plaque group (27 cases, 60%) and non-vulnerable plaque group (18 cases, 40%). PV-USS2D and PV-USS2D+CEUS in vulnerable plaque group were higher than those in non-vulnerable plaque group (PV-USS2D : 9.44 ± 2.10 vs 7.22 ± 1.73; PV-USS2D+CEUS: 12.37 ± 2.10 vs 8.28 ± 1.81, P < .001). ROC curve analysis showed that the AUC of PV-USS2D and PV-USSCEUS was 0.783 and 0.929, respectively (P < .001). The best cutoff values of PV-USS2D and PV-USS2D+CEUS were, respectively, 9.5 (the maximum Youden index was 0.425, the sensitivity was 48.1%, the specificity was 94.4%) and 10.5 (the maximum Youden index was 0.667, the sensitivity was 77.8%, the specificity was 88.9%). CONCLUSIONS: Ultrasound scoring system may be used as an effective method to evaluate the vulnerability of plaque. The diagnostic efficiency of PV-USS2D+CEUS is more higher than PV-USS2D .

α-Lipoic acid loaded hollow gold nanoparticles designed for osteoporosis treatment: preparation, characterization and in vitro evaluation.

Osteoporosis is a common disease among the ageing society. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) is the aetiology of osteoporosis. α-Lipoic acid (ALA) is an antioxidant in the body, which can eliminate excess ROS in the body and inhibits levels of oxidative stress in cells. Herein, we designed PEGylated hollow gold nanoparticles (HGNPs) loaded with ALA (mPEG@HGNPs-ALA) to remove ROS in the treatment of osteoporosis. First, mPEG@HGNPs with a particle size of ∼63 nm has been successfully synthesized. By comparing the drug loading of mPEG@HGNPs, it was concluded that the optimal mass ratio of mPEG@HGNPs (calculated by the amount of gold) to ALA was ∼1:2. ABTS antioxidant assay showed that free radical removal ability. In vitro results revealed that the preparation had good biocompatibility. At the gold concentration of 1-150 µg/mL, the cell viability of mPEG@HGNPs was more than 100%, which indicated that it could promote the proliferation of osteoblasts. What's more, mPEG@HGNPs-ALA could effectively remove the ROS caused by H2O2 injury and improve the cell viability. According to these results, it can be considered that mPEG@HGNPs-ALA has the potential to treat osteoporosis.

3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p.

The object was to enhance the bioactivity of pure polyether-ether-ketone (PEEK) by incorporating nano-TiO2 (n-TiO2) and investigate its potential mechanism. PEEK/n-TiO2 composite was manufactured using a 3D PEEK printer and characterized by scanning electron microscopy (SEM), 3D profiler, energy-dispersive spectroscopy, and Fourier-transform infrared (FT-IR) analyses. Cytocompatibility was tested using SEM, fluorescence, and cell counting kit-8 assays. Osteogenic differentiation was evaluated by osteogenic gene and mineralized nodule levels. The expression of the candidate miRNAs were detected in composite group, and its role in osteogenic differentiation was studied. As a results the 3D-printed PEEK/n-TiO2 composite (Φ = 25 mm, H = 2 mm) was successfully fabricated, and the TiO2 nanoparticles were well distributed and retained the nanoscale size of the powder. The Ra value of the composite surface was 2.69 ± 0.29, and Ti accounted for 22.29 ± 12.09% (in weight), and FT-IR analysis confirmed the characteristic peaks of TiO2. The cells in the composite group possessed better proliferation and osteogenic differentiation abilities than those in the PEEK group. miR-154-5p expression was decreased in the composite group, and the inhibition of miR-154-5p significantly enhanced the proliferation and osteogenic differentiation abilities. In conclusion, 3D-printed PEEK/n-TiO2 composite enhanced cytocompatibility and osteogenic induction ability by downregulating miR-154-5p, which provides a promising solution for improving the osteointegration of PEEK.

Low TLR and PSMA-TV predict biochemical response to abiraterone acetate in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage.

OBJECTIVE: To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. METHODS: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. RESULTS: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. CONCLUSIONS: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients.

Suspected allergy to titanium after anterior cervical discectomy and fusion using a Zero-P device: a case report.

PURPOSE: Cases of allergy to large surgical implants have been reported. However, few studies have reported allergy to small titanium-containing implants (e.g. Zero-P device). METHODS: We reported the case of a 51-year old male patient who underwent the anterior cervical discectomy and fusion (ACDF) procedure using a Zero-P device and exhibited allergic symptoms 1 month after the surgery. RESULTS: The allergic symptoms included intermittent tingling and itches in the throat induced by speaking. Systemic rashes over the skin surface and congestion of the eyeball, and dysphagia were also present. Anti-allergic treatment did not resolve the symptoms. Patch tests revealed negative reactions to the rested reagents including titanium. Radiographic results showed solid bone fusion and no signs of chronic inflammation or hypotoxic infection in the surrounding tissues. Upon the patient's request, we removed the titanium screws and plate of the Zero-P device. No allergic reactions were observed after the surgery and at a 6-month follow-up. CONCLUSIONS: Even with a small implant such as the Zero-P device, allergy to titanium may still occur. This case demonstrated the need to screen for the presence of allergy to metals including titanium before the surgery.

Biomechanical Analysis of Cortical Bone Trajectory Screw Versus Bone Cement Screw for Fixation in Porcine Spinal Low Bone Mass Model.

STUDY DESIGN: A prospective study of in vitro animal. OBJECTION: To compare the biomechanics of cortical bone trajectory screw (CBT) and bone cement screw (BC) in an isolated porcine spinal low bone mass model. SUMMARY OF BACKGROUND DATA: The choice of spinal fixation in patients with osteoporosis remains controversial. Is CBT better than BC? Research on this issue is lacking. METHODS: Ten porcine spines with 3 segments were treated with EDTA decalcification. After 8 weeks, all the models met the criteria of low bone mass. Ten specimens were randomly divided into groups, group was implanted with CBT screw (CBT group) and the other group was implanted with bone cement screw (BC group). The biomechanical material testing machine was used to compare the porcine spine activities of the two groups in flexion, extension, bending, and axial rotation, and then insertional torque, pull-out force, and anti-compression force of the 2 groups were compared. Independent sample t test was used for comparison between groups. RESULTS: Ten 3 segments of porcine spine models with low bone mass were established, and the bone mineral density of all models was lower than 0.75 g/cm 2 . There is no difference between the CBT and BC groups in flexion, extension, bending, and axial rotation angle, P >0.05. However, there were significant differences between the 2 groups and the control group, with P ＜0.01. The 2 groups significantly differed between the insertional torque ( P =0.03) and the screw pull-out force ( P =0.021). The anti-compression forces between the 2 groups have no significant difference between the two groups ( P =0.946). CONCLUSIONS: The insertional torque and pull-out force of the CBT were higher than those of the BC in the isolated low bone porcine spine model. The range of motion and anti-compression ability of the model was similar between the 2 fixation methods.

Casticin promotes osteogenic differentiation of bone marrow stromal cells and improves osteoporosis in rats by regulating nuclear factor-κB/mitogen-activated protein kinase.

BACKGROUND: Osteoporosis has influenced millions of people, especially postmenopausal women, which has become a big burden to the whole world. Although the diverse roles of casticin (CAS) on different diseases were identified, whether it was implicated with osteoporosis was unknown. METHODS: A rat model of osteoporosis was established through dexamethasone (DEX) treatment and a cell model reflecting the osteogenic and osteoclast induction was constructed in bone marrow stromal cells (BMSCs). The calcification at the late stage of induction was measured via Alizarin Red S staining. Western blot was applied to evaluate the levels of proteins. RESULTS: Hematoxylin and eosin staining revealed that the number of bone trabecular in DEX-induced osteoporosis rats was decreased, while increased doses of CAS treatment elevated the number of bone trabecular. CAS treatment alleviated DEX-induced osteoporosis in rats. Moreover, we found that CAS inhibited the nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) pathway. In addition, CAS promoted osteogenic differentiation of BMSCs and reduced osteoclastogenesis of bone marrow monocytes. Finally, CAS was observed to retard the receptor activator of NFκ-B ligand-induced NF-κB/MAPK pathway. CONCLUSION: CAS promoted osteogenic differentiation of BMSCs and improved osteoporosis in rats by regulating the NF-κB/MAPK pathway. This might shed a light into using CAS as a drug treating osteoporosis in the future.

Erratum: IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.65255.].

Postoperative Upper-limb Palsy After Posterior Percutaneous Endoscopic Cervical Foraminotomy and Discectomy.

BACKGROUND: Postoperative upper-limb palsy (ULP) is a serious complication after cervical spine surgery. ULP after posterior percutaneous endoscopic cervical foraminotomy and discectomy (PPCED) has not yet been reported. OBJECTIVE: To introduce cases of postoperative ULP after PPCED and associated risk factors. STUDY DESIGN: A single-center, retrospective, observational study. SETTING: Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China. METHODS: From January 2016 through January 2022, PPCED involving a total of 663 segments was performed in 610 patients with radiculopathy who were diagnosed with cervical radiculopathy or mixed cervical spondylosis caused by foraminal stenosis or posterolateral disc herniation. RESULTS: PPCED was successfully completed in 610 patients, 6 of whom (0.98%) developed ULP. Two patients were diagnosed with double-segment cervical nerve root canal stenosis (C4/5/6, C5/6/7) and 2 with migrated cervical disc soft herniation (a magnetic resonance image of one showed a migrated disc herniation downward from C4/5 in the sagittal plane; another showed this upward from C5/6); one patient was diagnosed with C5/6 intervertebral foraminal stenosis, and one had simple C4/5 lateral disc herniation. Postoperative ULP rates for C4/5 (2/30, 6.67%) and C5/6 (2/177, 1.13%) were much higher than those for the other levels. Anatomically, the width of the intervertebral foramen on computed tomography was 2.3 ± 1.12 mm in ULP cases, which was significantly lower than that in non-ULP cases (3.4 ± 1.83, P < 0.05). This suggests that preoperative foramen width correlates highly negatively with postoperative ULP incidence. LIMITATIONS: This was a single-center, retrospective, nonrandomized study with a low level of evidence. CONCLUSIONS: PPCED is a good treatment for cervical radiculopathy. The rate of postoperative ULP after PPCED is much lower than that after posterior cervical foraminotomy. Perturbation to the C5 (or C6) nerve root, thermal injury due to burr use or the radiofrequency applied, and marked foraminal stenosis are possible relevant factors associated with postoperative ULP.

Oblique lateral interbody fusion stand-alone vs. combined with percutaneous pedicle screw fixation in the treatment of discogenic low back pain.

Objective: Oblique lateral interbody fusion (OLIF) has unique advantages in the treatment of discogenic low back pain (DBP). However, there are few studies in this area, and no established standard for additional posterior internal fixation. The purpose of this study was to investigate the efficacy of OLIF stand-alone vs. combined with percutaneous pedicle screw fixation (PPSF) in the treatment of DBP. Methods: This retrospective case-control study included forty patients. All patients were diagnosed with DBP by discography and discoblock. Perioperative parameters (surgery duration, blood loss, and muscle damage), complications, Visual analog scale (VAS), and Oswestry Disability Index (ODI) were assessed. Imaging data including cage subsidence, cage retropulsion, fusion rate, and adjacent spondylosis degeneration (ASD) were analyzed. Results: There were 23 patients in the OLIF stand-alone group and 17 patients in the OLIF + PPSF group. The mean surgery duration, blood loss, and muscle damage in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group (P < 0.05). However, there was no significant difference in the average hospitalization time between the two groups (P > 0.05). There was no significant difference in the VAS and ODI scores between the two groups before surgery (P > 0.05), and VAS and ODI scores significantly improved after surgery (P < 0.05). The VAS and ODI scores in the OLIF stand-alone group were significantly better than those in the OLIF + PPSF group at 1 month (P < 0.05), While there was no significant difference between the two groups at 12 months and last follow up (P > 0.05). At the last follow-up, there was no significant difference in cage subsidence, fusion rate, ASD and complication rate between the two groups (P > 0.05). Conclusion: OLIF stand-alone and OLIF + PPSF are both safe and effective in the treatment of DBP, and there is no significant difference in the long-term clinical and radiological outcomes. OLIF stand-alone has the advantages of surgery duration, blood loss, muscle damage, and early clinical effect. More clinical data are needed to confirm the effect of OLIF stand-alone on cage subsidence and ASD. This study provides a basis for the clinical application of standard DBP treatment with OLIF.

Diagnosis and treatment of left ureteral injury as a rare complication of oblique lumbar interbody fusion surgery: a case report and literature review.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) surgery has been performed as a minimally invasive lateral lumbar fusion technique in recent years. Reports of operative complications of OLIF are limited, and there are fewer reports of ureteral injuries. CASE PRESENTATION: A 62-year-old Chinese woman diagnosed with "lumbar spondylolisthesis (L4 forward slip, I degree)" underwent OLIF treatment. The surgical decompression process was smooth, and the cage was successfully placed. After the expansion sleeve of OLIF was removed, clear liquid continuous outflow from the peritoneum was found. The patient was diagnosed with a ureteral injury. The urological surgeon expanded the original incision, and left ureteral injury anastomosis and ureteral stent implantation were performed. The patient was changed to the prone position and a percutaneous pedicle screw was placed in the corresponding vertebral body. The patient was indwelled with a catheter for 2 weeks, and regular oral administration of levofloxacin to prevent urinary tract infection. After 2 months, the double J tube was removed using a cystoscope. One year after surgery, the symptoms of lumbar back were significantly improved, and there were no urinary system symptoms. However, the patient needed an annual left ureter and kidney B-ultrasound. CONCLUSION: Ureteral injury is a rare complication and is easily missed in OLIF surgery. If the diagnosis is missed, the consequences can be serious. Patients should undergo catheterization before the operation and hematuria should be observed during the operation. We emphasize the careful use of surgical instruments to prevent intraoperative complications. In addition, after withdrawing the leaf in the operation, it is necessary to carefully observe whether a clear liquid continues to leak. If ureteral injury is found, one-stage ureteral injury repair operation should be performed to prevent ureteral stricture.

Identification of diagnostic mRNA biomarkers in whole blood for ankylosing spondylitis using WGCNA and machine learning feature selection.

Ankylosing spondylitis (AS) is a common inflammatory spondyloarthritis affecting the spine and sacroiliac joint that finally results in sclerosis of the axial skeleton. Aside from human leukocyte antigen B27, transcriptomic biomarkers in blood for AS diagnosis still remain unknown. Hence, this study aimed to investigate credible AS-specific mRNA biomarkers from the whole blood of AS patients by analyzing an mRNA expression profile (GSE73754) downloaded Gene Expression Omnibus, which includes AS and healthy control blood samples. Weighted gene co-expression network analysis was performed and revealed three mRNA modules associated with AS. By performing gene set enrichment analysis, the functional annotations of these modules revealed immune biological processes that occur in AS. Several feature mRNAs were identified by analyzing the hubs of the protein-protein interaction network, which was based on the intersection between differentially expressed mRNAs and mRNA modules. A machine learning-based feature selection method, SVM-RFE, was used to further screen out 13 key feature mRNAs. After verifying by qPCR, IL17RA, Sqstm1, Picalm, Eif4e, Srrt, Lrrfip1, Synj1 and Cxcr6 were found to be significant for AS diagnosis. Among them, Cxcr6, IL17RA and Lrrfip1 were correlated with severity of AS symptoms. In conclusion, our findings provide a framework for identifying the key mRNAs in whole blood of AS that is conducive for the development of novel diagnostic markers for AS.

Controlling sustained statins release in multi-layered composite scaffolds for healing of osteoporotic bone defects.

The risk of fragility fracture sharply increases due to the decreased bone mineral density and toughness in patients with osteoporosis (OP). The local use of bone tissue scaffolds with both mechanical stability and drug-delivery functionality is one of the key strategies for the efficient curing of OP. In this work, we reported a layer-by-layer constructing strategy to fabricate 3-D composite bone tissue scaffolds (eSTPS) by assembling ß-tri­calcium phosphate (ß-TCP)/polycaprolactone (PCL) microchips and lovastatin-loaded nanofiber membranes (eLOV/PCL). The eSTPS scaffolds show a strong and suited compressive strength as well as long-term delivery of lovastatin. The in vitro tests indicate well biocompatibility and alkaline phosphatase activity of the scaffolds. The eSTPS scaffolds were implanted into the femur of OP modeled rabbits. After 12 weeks curing, the bone parameters are significantly improved, meanwhile ingrowth of new bone and vascular-like tissue were observed. These results suggest the eSTPS scaffolds to be a promising candidate for the local treatment of OP.

IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor among adolescents and young adults. IRF7 belongs to the transcription factor family of interferon regulatory factors (IRFs) and has previously been described to function as a tumor suppressor in multiple cancer types. However, the biological functions and cellular mechanism of IRF7 in OS remain elusive. In this study, by quantitative real-time PCR (qRT-PCR) and western blotting, we found that IRF7 was downregulated in OS, and the higher expression of IRF7 was correlated with a better survival prognosis. Moreover, loss-of-function and gain-of-function studies have proved the critical functions of IRF7 in suppressing aerobic glycolysis of osteosarcoma cells as evidenced by glucose uptake, lactate production, extracellular acidification rate, and oxygen consumption rate. Mechanistically, IRF7 inhibited the expression of key glycolytic gene PKM2 via direct transcriptional regulation. Moreover, the in vitro and in vivo tumor-suppressive roles of IRF7 were uncovered in OS and these effects were largely glycolysis-dependent. Therefore, our study unveils a previous unprecedented role of IRF7 in glucose metabolism reprogram and suggests that IRF7 might serve as a potential therapeutic target for patients with OS.