Comparison of Outcomes Between Endoscopic Transforaminal Lumbar Interbody Fusion and Minimally Invasive Transforaminal Lumbar Interbody Fusion in Patients With Single-Level Lumbar Degenerative Disease: A Retrospective Study.

OBJECTIVE: The objective of this study was to compare the clinical and radiological outcomes of endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: This retrospective study included 110 patients with single-level lumbar degenerative disease who underwent Endo-TLIF or MIS-TLIF between January 2019 and December 2021. Patients were divided into Endo-TLIF (n = 55) and MIS-TLIF groups (n = 55). Perioperative, clinical, and radiological outcomes were assessed. RESULTS: The Endo-TLIF group had significantly lower blood loss and shorter hospital stay. However, the operation time was significantly longer and there was more x-ray exposure than in the MIS-TLIF group. There were no significant differences in complications between the groups. The Endo-TLIF group showed significantly lower creatine kinase levels than the MIS-TLIF group at 3 days postoperatively (P < 0.05), but not at 7 days postoperatively (P > 0.05). Oswestry Disability Index and visual analog scale scores were significantly reduced in both groups at different time points postoperation compared to preoperation. The visual analog scale score in the Endo-TLIF group was lower than that in the MIS-TLIF group at 3 days postoperatively. Moreover, no significant differences were found in fusion rates, lumbar lordosis, and lumbar segmental lordosis between the 2 groups (P > 0.05). CONCLUSIONS: Endo-TLIF might be considered as an effective and reliable treatment option for single-level lumbar degeneration. It results in less trauma and faster postoperative recovery, but a longer operative time and more x-ray exposure than MIS-TLIF. Endo-TLIF has effects on clinical and radiological outcomes that are comparable to those of MIS-TLIF.

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.

Risk factors associated with the prevalence of neck and shoulder pain among high school students: a cross-sectional survey in China.

BACKGROUND: After the COVID-19 outbreak, many Chinese high school students have increased their dependence on electronic devices for studying and life, which may affect the incidence of neck and shoulder pain (NSP) in Chinese adolescents. METHODS: To evaluate the prevalence of NSP in high school students and its associated risk factors during COVID-19, a survey was conducted among 5,046 high school students in Shanghai, Qinghai, Henan and Macao during the second semester and summer vacation of the 2019-2020 academic year. The questionnaire included questions regarding demographic characteristics, the prevalence of NSP and lifestyle factors such as sedentary behavior, poor posture and electronic device usage. Univariable and multivariable logistic regression was used to analyze the possible influencing factors for neck and shoulder pain. RESULTS: A total of 4793 valid questionnaires (95.0%) were collected. The results indicated that the prevalence of NSP was 23.7% among high school students. Binary logistic regression analysis revealed that female gender (P < 0.05, OR = 1.82), grade (P < 0.05, range OR 1.40-1.51) and subject selection (P < 0.05, range OR 0.49-0.68) were risk factors for NSP in high school students. Sedentary behavior (P < 0.05, range OR 1.74-2.36), poor posture (P < 0.05, range OR 1.19-2.56), backpack weight (P < 0.05, range OR 1.17-1.88), exercise style and frequency (P < 0.05, range OR 1.18-1.31; P < 0.05, range OR 0.76-0.79, respectively), and the time spent using electronic devices (P < 0.05, range OR 1.23-1.38)had a significant correlation with NSP in high school students. CONCLUSIONS: NSP is currently very common among high school students during the outbreak of COVID-19. Sedentary behavior, poor posture and other factors have a great impact on the occurrence of NSP in high school students. Education regarding healthy lifestyle choices should be advocated for to decrease NSP among high school students, such as more physical activity, changing poor postures and reducing the amount of time spent using electronic devices.

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.

Hydrogen Promotes the Effectiveness of Bone Mesenchymal Stem Cell Transplantation in Rats with Spinal Cord Injury.

Although bone mesenchymal stem cell (BMSC) transplantation has been applied to the treatment of spinal cord injury (SCI), the effect is unsatisfactory due to the specific microenvironment (inflammation and oxidative stress) in the SCI area, which leads to the low survival rate of transplanted cells. Thus, additional strategies are required to improve the efficacy of transplanted cells in the treatment of SCI. Hydrogen possesses antioxidant and anti-inflammatory properties. However, whether hydrogen can enhance the effect of BMSC transplantation in the treatment of SCI has not yet been reported. This study was aimed at investigating whether hydrogen promotes the therapeutic effect of BMSC transplantation in the treatment of SCI in rats. In vitro, BMSCs were cultured in a normal medium and a hydrogen-rich medium to study the effect of hydrogen on the proliferation and migration of BMSCs. BMSCs were treated with a serum-deprived medium (SDM), and the effects of hydrogen on the apoptosis of BMSCs were studied. In vivo, BMSCs were injected into the rat model of SCI. Hydrogen-rich saline (5 ml/kg) and saline (5 ml/kg) were given once a day via intraperitoneal injection. Neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) and CatWalk gait analyses. Histopathological analysis, oxidative stress, inflammatory factors (TNF-α, IL-1ß, and IL-6), and transplanted cell viability were detected at 3 and 28 days after SCI. Hydrogen can significantly enhance BMSC proliferation and migration and tolerance to SDM. Hydrogen and BMSC codelivery can significantly enhance neurological function recovery by improving the transplant cell survival rate and migration. Hydrogen can enhance the migration and proliferation capacity of BMSCs to repair SCI by reducing the inflammatory response and oxidative stress in the injured area. Hydrogen and BMSC codelivery is an effective method to improve BMSC transplantation in the treatment of SCI.

Expanding the "Magic Triangle" of Reinforced Rubber Using a Supramolecular Filler Strategy.

A strategy for optimizing the rolling resistance, wet skid and cut resistance of reinforced rubber simultaneously using a supramolecular filler is demonstrated. A ß-alanine trimer-grafted Styrene Butadiene Rubber (A3-SBR) pristine polymer was designed and mechanically mixed with commercially available styrene butadiene rubber to help the dispersion of a ß-alanine trimer (A3) supramolecular filler in the rubber matrix. To increase the miscibility of A3-SBR with other rubber components during mechanical mixing, the pristine polymer was saturated with ethanol before mixing. The mixture was vulcanized using a conventional rubber processing method. The morphology of the assembles of the A3 supramolecular filler in the rubber matrix was studied by Differential Scanning Calorimetry (DSC) and Transmission Electron Microscopy (TEM). The Differential Scanning Calorimetry study showed that the melting temperature of ß-sheet crystals in the vulcanizates was around 179 °C and was broad. The melting temperature was similar to that of the pristine polymer, and the broad melting peak likely suggests that the size of the crystals is not uniform. The Transmission Electron Microscopy study revealed that after mixing the pristine polymer with SBR, some ß-sheet crystals were rod-like with several tens of nanometers and some ß-sheet crystals were particulate with low aspect ratios. Tensile testing with pre-cut specimens showed that the vulcanizate containing A3-SBR was more cut-resistant than the one that did not contain A3-SBR, especially at a large cut size. The rolling resistance and wet skid were predicted by dynamic mechanical analysis (DMA). DMA tests showed that the vulcanizates containing A3-SBR were significantly less hysteretic at 60 °C and more hysteretic at 0 °C based on loss factor. Overall, the "magic triangle" was expanded by optimizing the rolling resistance, wet-skid, and cut resistance simultaneously using a ß-alanine trimer supramolecular filler. The Payne effect also became less severe after introducing the ß-alanine trimer supramolecular filler into the system.

Multiband Signal Receiver by Using an Optical Bandpass Filter Integrated with a Photodetector on a Chip.

Photonic integration brings the promise of significant cost, power and space savings and propels the real applications of microwave photonic technology. In this paper, a multiband radio frequency (RF) signal simultaneous receiver using an optical bandpass filter (OBPF) integrated with a photodetector (PD) on a chip is proposed, which was experimentally demonstrated. The OBPF was composed of ring-assisted Mach-Zehnder interferometer with a periodical bandpass response featuring a box-like spectral shape. The OBPF was connected to a PD and then integrated onto a single silicon photonic chip. Phase-modulated multiband RF signals transmitted from different locations were inputted into the OBPF, by which one RF sideband was filtered out and the phase modulation to intensity modulation conversion was realized. The single sideband with carrier signals were then simultaneously detected by the PD. A proof-of-concept experiment with the silicon photonic integrated chip was implemented to simultaneously receive four channels of 8 GHz, 12 GHz, 14 GHz and 18 GHz in the X- and Ku-bands. The performance of the integrated microwave photonic multiband receiver-including the receiving sensitivity, the spurious free dynamic range, the gain and the noise figure across the whole operation frequency band-was characterized in detail.

pH-Responsive Delivery of H2 through Ammonia Borane-Loaded Hollow Polydopamine for Intervertebral Disc Degeneration Therapy.

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 µg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (P < 0.05). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.

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.

Effect of species, concentration and volume of local anesthetics on intervertebral disk degeneration in rats with discoblock.

PURPOSE: Discoblock is effective in relieving discogenic low back pain, but it can also cause intervertebral disk degeneration (IDD). The effect of species, concentration and volume of local anesthetics on IDD with discoblock have not been reported. The purpose was to study the effect of species, concentration and volume of local anesthetics on IDD in rats undergoing discoblock. METHODS: The effects of local anesthetics on nucleus pulposus cell (NPC) viability in vitro were studied. NPCs were exposed to lidocaine, bupivacaine and ropivacaine at different concentrations. NPC viability was measured. The least cytotoxic local anesthetic was used in vivo. The concentration and volume of local anesthetics on IDD in rat with discoblocks were tested in vivo. Detection indicators included X-ray, MRI, water content of the disk and histological changes. RESULTS: The toxicity of local anesthetics to NPCs was dose and time dependent, and the cytotoxicity of different local anesthetics was different. Among the three local anesthetics, ropivacaine was the least toxic to NPCs. The effect of ropivacaine concentration on IDD was not significant, as detected by X-ray, MRI, disk water content and histology (P < 0.05). The volume of ropivacaine has a significant effect on IDD, as supported by X-ray, MRI, disk water content and histology (P < 0.05). Acupuncture itself significantly increased IDD, as detected by MRI, disk water content and histology (P < 0.05). CONCLUSION: Ropivacaine should be selected for its low cytotoxicity. A lower volume and slow injection speed should be used to reduce IDD during discoblock.

Alendronate-functionalized double network hydrogel scaffolds for effective osteogenesis.

Development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. In views of the actual requirement of biomechanics, biodegradability, and bioactivity, herein, a double-network (DN) hydrogel was constructed by interspersing a methacrylated gelatin (GelMA) network into alendronate (ALN)-modified oxidized alginate (OSA) network via Schiff base reaction and photo-crosslinking process to promote in situ bone regeneration. This GelMA@OSA-ALN DN hydrogel possessed favorable network and pores, good biocompatibility, and enhanced biomechanics. Notably, the introduction of Schiff base furnished the ND hydrogel scaffold with pH-responsive biodegradation and sustained ALN drug release delivery, which could provide effective bioactivity, upregulate osteogenesis-related genes, and promote the cell viability, growth, proliferation, and osteogenesis differentiation for bone regeneration. Therefore, we provide a new insight to develop functional DN hydrogel scaffold toward governing the on-demand drug release and achieving the stem cell therapy, which will be developed into the minimally invasive gelling system to prolong local delivery of bisphosphonates for the bone-related diseases.

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats.

Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (-23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10-200 µg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.

Fabrication of Naturally Derived Double-Network Hydrogels With a Sustained Aspirin Release System for Facilitating Bone Regeneration.

Continuous efforts on pursuit of effective drug delivery systems for engineering hydrogel scaffolds is considered a promising strategy for the bone-related diseases. Here, we developed a kind of acetylsalicylic acid (aspirin, ASA)-based double-network (DN) hydrogel containing the positively charged natural chitosan (CS) and methacrylated gelatin (GelMA) polymers. Combination of physical chain-entanglement, electrostatic interactions, and a chemically cross-linked methacrylated gelatin (GelMA) network led to the formation of a DN hydrogel, which had a suitable porous structure and favorable mechanical properties. After in situ encapsulation of aspirin agents, the resulting hydrogels were investigated as culturing matrices for adipose tissue-derived stromal cells (ADSCs) to evaluate their excellent biocompatibility and biological capacities on modulation of cell proliferation and differentiation. We further found that the long-term sustained ASA in the DN hydrogels could contribute to the anti-inflammation and osteoinductive properties, demonstrating a new strategy for bone tissue regeneration.

Myricetin Loaded Nano-micelles Delivery System Reduces Bone Loss Induced by Ovariectomy in Rats Through Inhibition of Osteoclast Formation.

In recent years, much attention has been paid to the therapeutic effects of phytochemicals on osteoporosis. Other studies have shown that myricetin (MY) could promote osteogenic activity and inhibit osteoclastic effect, albeit little is known about effect of MY micellar system on osteoporosis. Therefore, we sought to discuss the therapeutic effect and mechanism of MY-loaded bone-targeting micelles on osteoporosis induced by ovariectomy (OVA) in rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles were prepared via ethanol injection method, while in vitro release study, bone targeting, pharmacokinetic studies, and the effect on proliferation of osteoblasts were investigated. Further, the therapeutic effect on osteoporosis was studied through ovariectomized rats. Compared with free MY, oral bioavailability of AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles in rats was increased by 3.54 times. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles exhibited bone targeting potential, and could significantly increase the activity of alkaline phosphatase and promote the proliferation of osteoblasts. Importantly, AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles mainly regulated bone metabolism by inhibiting bone resorption, thereby improving the symptoms of osteoporosis in OVA rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles substantially enhanced the oral bioavailability of MY and demonstrated good bone targeting capability, thereby suggesting its prospect as carrier for osteoporotic improvement in OVA rats.

Morphology of Herniated Disc as a Predictor for Outcomes of Posterior Percutaneous Full-endoscopic Cervical Discectomy in Treating Cervical Spondylotic Radiculopathy.

OBJECTIVE: To quantitively characterize the morphology of cervical disc herniation (CDH) causing cervical spondylotic radiculopathy (CSR) and investigate whether the morphological features of CDH are associated with clinical outcomes in CSR patients treated by posterior percutaneous full-endoscopic cervical discectomy (PPECD). METHODS: This is a single-center retrospective study. Eighty-seven PPECD-treated patients meeting the inclusion criteria were included between May 2017 and May 2019. Based on preoperative T2-weighted magnetic resonance imaging (MRI), we designed and measured six morphological parameters of CDH for all patients to reflect its relative position to cervical spinal cord and protruding degree: DC-SC distance from the center of disc (DC) and the center of spinal cord (SC); DC-DP distance from the center of cervical disc (DC) to the peak of herniation (DP); internal diameter of the disc; axial length of CDH; central angle of CDH formed by central axes of CDH and spinal cord; the modified index of CDH. We recorded general information, neck disability index (NDI) scores, visual analog scale (VAS) scores of neck and arm of all patients preoperatively and postoperatively at 1-year follow-up. The association of preoperative general variables and morphological parameters with clinical outcomes were explored by utilizing logistic regression and receiver operating characteristic curve (ROC) analysis. RESULTS: The preoperative neck-VAS, arm-VAS, and NDI were significantly decreased after PPECD and remained at a low value at follow-up. In regards to the morphological parameters of CDH, the mean value of DC-SC distance, DC-DP distance, internal diameter of the disc, axial length of CDH, central angle of CDH, and modified index of CDH were 1.61 ± 0.30 cm, 1.66 ± 0.32cm, 1.04 ± 0.21 cm, 0.63 ± 0.19cm, 39.38° ± 11.94°, and 0.39 ± 0.24, respectively. For patients grouped by difference in the recovery rate of NDI and arm-VAS (excellent improved group, EI; and limited improved group, LI), there were no differences in the age, gender, surgical segments, and morphological parameters, except for the central angle of CDH. According to binary logistic regression analysis, only the preoperative central angle of CDH was significantly associated with postoperative NDI recovery (odds ratio: 0.873; 95% confidence interval: 0.819-0.931, P = 0.002). ROC analysis showed the optimal cut-off value of the central angle of CDH for predicting the postoperative improvement of functional outcomes is 33.788°. CONCLUSION: Preoperative morphology of CDH is related to the outcomes of CSR patients after PPECD. Patients with a large central angle of CDH (>33.788°) have more likelihood of ameliorating neurological symptoms of CSR. There is the potential to select the central angle of CDH as a predictor for outcomes of PPECD in treating CSR.

Central nystagmus plus ABCD2 identifying stroke in acute dizziness presentations.

OBJECTIVE: The objective was to explore the ability of head impulse-nystagmus-test of skew (HINTS) combined with ABCD2  score to identify cerebrovascular causes of dizziness. MATERIALS AND METHODS: We prospectively recruited 85 patients with acute onset of dizziness from September 2016 to December 2018 and analyzed their clinical characteristics, ABCD2  scores, HINTS, and neuroimages data. RESULTS: Acute stroke was identified by MRI in 21 of 85 patients. The mean ± SD ABCD2  scores were significantly higher among patients with acute stroke than those without acute stroke (4.0 ± 0.8 h vs. 2.5 ± 0.7 h, p < 0.01). The majority (71.4%) of patients with cerebrovascular causes had central pattern of nystagmus at the initial 48 h from symptoms onset. The sensitivity and specificity of HINTS were 100% and 87% for the presence of stroke in patients with nystagmus. When combined central pattern of nystagmus and ABCD2  ≥ 4, the sensitivity increased to 100% for identifying cerebrovascular causes. Nystagmus were absence at time of examination in 16.5% of our patients, and ABCD2  scores in patients who had cerebrovascular diagnoses were all ≥ 4. CONCLUSION: HINTS examinations could efficiently differentiate stroke from nonstroke under the condition that patients remaining symptomatic, including spontaneous or gaze-evoked nystagmus. It is more practical to apply the combination of central pattern of nystagmus and ABCD2  ≥ 4 in ED setting. If patients were absence of central nystagmus at admission, cerebrovascular event should be a priority diagnosis when their ABCD2  ≥ 4.

Toxicology and Pharmacokinetics Study of Intradiscal Injection of Simvastatin in Rabbits.

To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups: control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 µl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p > 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p < 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.

The Effect and Possible Mechanism of Intradiscal Injection of Simvastatin in the Treatment of Discogenic Pain in Rats.

To study the effect of intradiscal injection of simvastatin on discogenic pain in rats and its possible mechanism, 30 adult female rats were used in this experiment. Twenty rats were randomly divided into sham operation group (Control group), intervertebral disk degeneration group (DDD group), intervertebral disk degeneration + hydrogel group (DDD + GEL group), and intervertebral disk degeneration + simvastatin group (DDD + SIM group). The mechanical pain threshold and cold sensation in rats were measured. The contents of NF-kappa B1, RelA, GAP43, SP, CGRP, TRPM 8, IL-1ß, and TNF-α in the intervertebral disk (IVD), the corresponding contents of dorsal root ganglion (DRG) and plantar skin GAP43 and TRPM 8 were quantitatively detected by PCR. The corresponding IVDs were stained to detect their degeneration. There was no significant difference in the mechanical pain threshold between the groups at each time point. From the first day to the 8th week after surgery, the cold-sensing response of the DDD group was significantly higher than that of the Control group (P < 0.05). At 7 and 8 weeks postoperatively, the cold-sensing response of the DDD + SIM group was significantly lower than that of the DDD + GEL group (P < 0.05). The levels of NF-κB1, RelA, GAP43, SP, CGRP, TRPM8, IL-1ß, and TNF-α in the IVD of DDD + SIM group were significantly lower than those in DDD group (P < 0.05). The content of GAP43 and TRPM8 in rat plantar skin decreased significantly and TRPM8 in DRG decreased significantly (P < 0.05).