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.

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.

Clinical features and outcomes of benign recurrent vertigo: A longitudinal study.

OBJECTIVE: To study the demographics, vertigo profiles, and outcomes of adult patients with benign recurrent vertigo (BRV). PATIENTS AND METHODS: This prospective study included patients with BRV who were admitted to a tertiary neurology clinic between June 2013 and June 2017. All patients underwent detailed clinical interviews and related examinations. A follow-up was then conducted through an outpatient or telephone interview. RESULTS: A total of 66 patients (48 females) were enrolled, and the mean age at the onset of vertigo was 35.2 years. Spontaneous vertigo was the most common type (77.8%), followed by positional vertigo (16.7%). The duration of vertigo attacks varied from minutes to 72 hours. A family history of migraine and/or recurrent vertigo was reported in 51.5% of patients. The overall response rate was 80.3%（53/66）after a median follow-up time of 32.5 months (range: 18-60 months). Forty (75.5%, of 53) patients still reported having vertigo attacks at the follow-up. The frequency of vertigo attacks was reduced in 32 (60.4%) patients and was unchanged in 8 (15.1%). Four (7.5%) cases developed into vestibular migraine, but none developed into Meniere's disease. CONCLUSION: The outcomes of patients with BRV were benign, and the frequency of vertigo is significantly reduced. Few cases developed into vestibular migraine.

Standalone oblique lateral interbody fusion vs. combined with percutaneous pedicle screw in spondylolisthesis.

BACKGROUND: To compare standalone oblique lateral interbody fusion (OLIF) vs. OLIF combined with posterior bilateral percutaneous pedicle screw fixation (OLIF combined) for the treatment of lumbar spondylolisthesis. METHODS: This was a retrospective study of patients who underwent standalone OLIF or combined OLIF between 07/2014 and 08/2017 at two hospitals in China. Direct decompressions were not performed. Visual analog scale (VAS), Oswestry Disability Index (ODI), satisfaction rate, anterior/posterior disc heights (DH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, fusion rate, and complications were analyzed. All imaging examinations were read independently by two physicians and the mean measurements were used for analysis. RESULTS: A total of 73 patients were included: 32 with standalone OLIF and 41 with combined OLIF. The total complication rate was 25.0% with standalone OLIF and 26.8% with combined OLIF. There were no differences in VAS and ODI scores by 2 years of follow-up, but the scores were better with standalone OLIF at 1 week and 3 months (P < 0.05). PDH and FW was smaller in the combined OLIF group compared with the standalone OLIF group before and after surgery (all P < 0.05). There were significant differences in FH before surgery and at 1 week and 3 months between the two groups (all P < 0.05), but the difference disappeared by 2 years (P = 0.111). Cage subsidence occurred in 7.3% (3/41) and 7.3% (3/41) of the patients at 3 and 24 months, respectively, in the combined OLIF group, compared with 6.3% (2/32) and 15.6% (5/32), respectively, in the standalone OLIF group at the same time points (P = 0.287). There was no cage retropulsion in both groups at 2 years. The fusion rate was 85.4%(35/41) in the combined OLIF group and 84.4% (27/32) in the standalone OLIF group at 3 months(P = 0.669). At 24 months, the fusion rate was 100.0% in the combined OLIF group and 93.8% (30/32) in the standalone OLIF group (P = 0.066). CONCLUSION: Standalone OLIF may achieve equivalent clinical and radiological outcomes than OLIF combined with fixation for spondylolisthesis. The rate of complications was similar between the two groups. Patients who are osteoporotic might be better undergoing combined rather than standalone OLIF. The possibilty of proof lies within a future prospective study, preferably an RCT.

Quantitative analysis of paraspinal muscle atrophy after oblique lateral interbody fusion alone vs. combined with percutaneous pedicle screw fixation in patients with spondylolisthesis.

BACKGROUND: There is no available literature for comparison on muscle atrophy between the "stand-alone" oblique lateral interbody fusion (OLIF) and regular OLIF (i.e., combined with percutaneous pedicle screws fixation (PPSF) in patients with spondylolisthesis). This study aimed to identify changes in back muscle atrophy between the two surgeries. METHODS: This was a retrospective cohort study of patients who underwent OLIF or OLIF+PPSF at Beijing Jishuitan Hospital and Shanghai ChangZheng Hospital between 07/2014 and 10/2017. Computed tomography (CT) was used to measure functional cross-sectional area (FCSA) and fat infiltration percentage (FIP) of the multifidus and erector spinae before and 24 months after surgery. RESULT: There were no differences in FCSA and FIP between OLIF (n = 32) and OLIF+PPSF (n = 41) groups before surgery. In the OLIF group, the multifidus and erector spinae FCSA and FIP did not change at 24 months (FCSA: multifidus: from 8.59 ± 1.76 to 9.39 ± 1.74 cm2, P = 0.072; erector spinae: from 13.32 ± 1.59 to 13.55 ± 1.31 cm2, P = 0.533) (FIP: multifidus: from 15.91 ± 5.30% to 14.38 ± 3.21%, P = 0.721; erector spinae: from 11.63 ± 3.05% to 11.22 ± 3.12%, P = 0.578). In the OLIF+PPSF group, the multifidus and erector spinae FCSA decreased (multifidus: from 7.72 ± 2.69 to 5.67 ± 1.71 cm2, P < 0.001; erector spinae: from 12.60 ± 2.04 to 10.15 ± 1.82 cm2, P < 0.001), while the FIP increased (multifidus: from 16.13 ± 7.01% to 49.38 ± 20.54%, P < 0.001; erector spinae: from 11.93 ± 3.22% to 22.60 ± 4.99%, P < 0.001). The differences of FCSA and FIP between the two groups at 24 months were significant (all P < 0.001). The patients in the standalone OLIF group had better VAS back pain, and JOA scores than the patients in the OLIF combined group (all P < 0.05) at 1 week and 3 months after surgery. There were two cases (4.9%) of adjacent segment degeneration in the OLIF combined group, while there was no case in the OLIF alone group. CONCLUSIONS: Standalone OLIF had better clinical outcomes at 1 week and 3 months than OLIF+PPSF in patients with spondylolisthesis. OLIF may not result in paraspinal muscle atrophy at 24 months after surgery.

Removal of calcified lumbar disc herniation with endoscopic-matched ultrasonic osteotome - Our preliminary experience.

Objective: To evaluate the clinical efficacy, practicability, and safety of an ultrasonic osteotome for percutaneous transforaminal endoscopic discectomy (PTED) in patients with calcified lumbar disc herniation (CLDH).Methods: A total of 25 CLDH patients who underwent PTED at our department between December 2017 and August 2018 were analyzed retrospectively. Post-operative lumbar spine CT was used to evaluate residual calcification. Efficacy was evaluated by pre- and post-operative with the pain visual analog scale (VAS), Oswestry disability index (ODI), and the Modified MacNab Scale; the incidence of intra- and postoperative complications was also analyzed.Results: All procedures were successfully completed and none of the patients was lost to follow-up. Postoperative CT verified the successful removal of calcified protrusions. VAS and ODI scores improved significantly after surgery. Based on the Modified MacNab scale, >90% patients achieved good or excellent outcomes. There were no complications such as dural tear and infection. Seven patients had varying degrees of postoperative dysesthesia. One patient experienced recurrence of herniation within 1 week after operation; successful recovery was achieved after repeat PTED.Conclusions: Use of this ultrasonic osteotome for PTED facilitated effective removal of calcified disc protrusion, relieved nerve compression, and protected the adjacent neurovascular tissues. The instrument may help expand the indications for endoscopic surgery and avoid open surgery for some CLDH patients.

Tunability of Hi-Bi photonic crystal fiber integrated with selectively filled magnetic fluid and microfluidic manipulation.

Optical fiber microfluidics technology can implement the mutual tune of the light field and fluid in micro-nano scale. In this paper, one core of high-birefringence photonic crystal fiber (Hi-Bi PCF) is used as a microfluidic channel. The birefringence of Fe3O4 nanofluid is experimentally and theoretically investigated by selectively infiltrating the magnetic fluid into the core of the Hi-Bi PCF. The presence of magnetic fluid alters the birefringence of the original Hi-Bi PCF and can be modulated by the intensity of the external magnetic field. The optical field distribution is simulated, and the birefringence of the Hi-Bi PCF with selective filling is approximately 6.672×10-4. The experimental results show that the structure has a highly linear response to the external magnetic field from 0 Oe to 300 Oe, and the sensitivity is 16.8 pm/Oe with a high resolution of 1.19 Oe. Due to several advantages such as all-fiber compact structure, low transmission loss, and high linear response, this device can find various applications, including weak magnetic field measurement with high accuracy, optical fiber gyroscopes, and magneto-optic modulators. Particularly, it also has important significance to realize the all-fiber microfluidic chip laboratory.

Effect of needle diameter, type and volume of contrast agent on intervertebral disc degeneration in rats with discography.

PURPOSE: Discography can increase disc degeneration, but the influence of different discography variables on the degeneration of discs has not been reported. The aim of this study was to investigate the effects of discography variables of needle diameter, type of contrast agent and volume of contrast agent on disc degeneration. METHODS: Three separate experiments examined needle diameter, and type and volume of contrast agent. Coccygeal discs (Co7-10) adult male rats were used. X-rays were used to detect the disc height degeneration index at 1, 2 and 4 weeks after the procedure. MRI was used to study the changes in the disc structure and the signal intensity of IVD 2 and 4 weeks after the procedure. Disc water content and histology were measured at 4 weeks after the procedure. RESULTS: A 21-g needle significantly increased disc degeneration when compared with the 30-g needle as detected by X-ray, MRI, disc water content and histology (P < 0.05). Two microlitres of iodine significantly decreased the disc MRI signal and water content at 4 weeks compared with the same volume of normal saline (P < 0.05). Three microlitres of iodine significantly increased disc degeneration when compared with 2 µl iodine, as detected by X-ray, MRI, disc water content and histology at 4 weeks (P < 0.05). CONCLUSION: To reduce disc degeneration after discography, it may be best to choose a smaller needle size, minimize the use of contrast agent and use non-ionic contrast agents with osmotic pressure similar to the intervertebral disc. These slides can be retrieved under Electronic Supplementary Material.

Bone mesenchymal stem cells attenuate radicular pain by inhibiting microglial activation in a rat noncompressive disk herniation model.

Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses. Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflammation and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). The study found that the use of NP in the DRG can induce abnormal mechanical pain, increase the contents of the proinflammatory factors TNF-α and IL-1ß, decrease the content of the anti-inflammatory cytokine TGF-ß1 and activate microglia in the spinal dorsal horns (L5) (P < 0.05). BMSC administration could increase the mechanical withdrawal thresholds dramatically, decrease the contents of IL-1ß and TNF-α, increase the content of TGF-ß1 significantly (P < 0.05) and inhibit microglial activation in the bilateral spinal dorsal horn. Our results indicate that BMSC administration can reduce mechanical allodynia and downregulate the expression of proinflammatory cytokines by inhibiting microglial activation in the spinal dorsal horn in a rat noncompressive disk herniation model.

Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates.

siRNA therapeutics have promise for the treatment of a wide range of genetic disorders. Motivated by lipoproteins, we report lipopeptide nanoparticles as potent and selective siRNA carriers with a wide therapeutic index. Lead material cKK-E12 showed potent silencing effects in mice (ED50 ∼ 0.002 mg/kg), rats (ED50 < 0.01 mg/kg), and nonhuman primates (over 95% silencing at 0.3 mg/kg). Apolipoprotein E plays a significant role in the potency of cKK-E12 both in vitro and in vivo. cKK-E12 was highly selective toward liver parenchymal cell in vivo, with orders of magnitude lower doses needed to silence in hepatocytes compared with endothelial cells and immune cells in different organs. Toxicity studies showed that cKK-E12 was well tolerated in rats at a dose of 1 mg/kg (over 100-fold higher than the ED50). To our knowledge, this is the most efficacious and selective nonviral siRNA delivery system for gene silencing in hepatocytes reported to date.

Poly(glycoamidoamine) Brushes Formulated Nanomaterials for Systemic siRNA and mRNA Delivery in Vivo.

Safe and effective delivery is required for siRNA and mRNA-based therapeutics to reach their potential. Here, we report on the development of poly(glycoamidoamine) brush nanoparticles as delivery vehicles for siRNA and mRNA. These polymers were capable of significant delivery of siRNA against FVII and mRNA-encoding erythropoietin (EPO) in mice. Importantly, these nanoparticles were well-tolerated at their effective dose based on analysis of tissue histology, systemic cytokine levels, and liver enzyme chemistry. The polymer brush nanoparticles reported here are promising for therapeutic applications.

Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid-Glucose Complexation.

Injectable hydrogels have been widely used for a number of biomedical applications. Here, we report a new strategy to form an injectable and glucose-responsive hydrogel using the boronic acid-glucose complexation. The ratio of boronic acid and glucose functional groups is critical for hydrogel formation. In our system, polymers with 10-60% boronic acid, with the balance being glucose-modified, are favorable to form hydrogels. These hydrogels are shear-thinning and self-healing, recovering from shear-induced flow to a gel state within seconds. More importantly, these polymers displayed glucose-responsive release of an encapsulated model drug. The hydrogel reported here is an injectable and glucose-responsive hydrogel constructed from the complexation of boronic acid and glucose within a single component polymeric material.

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.

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.

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.

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.

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.

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.