Osteopontin deficiency promotes cartilaginous endplate degeneration by enhancing the NF-κB signaling to recruit macrophages and activate the NLRP3 inflammasome.

Intervertebral disc degeneration (IDD) is a major cause of discogenic pain, and is attributed to the dysfunction of nucleus pulposus, annulus fibrosus, and cartilaginous endplate (CEP). Osteopontin (OPN), a glycoprotein, is highly expressed in the CEP. However, little is known on how OPN regulates CEP homeostasis and degeneration, contributing to the pathogenesis of IDD. Here, we investigate the roles of OPN in CEP degeneration in a mouse IDD model induced by lumbar spine instability and its impact on the degeneration of endplate chondrocytes (EPCs) under pathological conditions. OPN is mainly expressed in the CEP and decreases with degeneration in mice and human patients with severe IDD. Conditional Spp1 knockout in EPCs of adult mice enhances age-related CEP degeneration and accelerates CEP remodeling during IDD. Mechanistically, OPN deficiency increases CCL2 and CCL5 production in EPCs to recruit macrophages and enhances the activation of NLRP3 inflammasome and NF-κB signaling by facilitating assembly of IRAK1-TRAF6 complex, deteriorating CEP degeneration in a spatiotemporal pattern. More importantly, pharmacological inhibition of the NF-κB/NLRP3 axis attenuates CEP degeneration in OPN-deficient IDD mice. Overall, this study highlights the importance of OPN in maintaining CEP and disc homeostasis, and proposes a promising therapeutic strategy for IDD by targeting the NF-κB/NLRP3 axis.

Maglev-fabricated long and biodegradable stent for interventional treatment of peripheral vessels.

While chronic limb-threatening ischemia is a serious peripheral artery disease, the lack of an appropriate stent significantly limits the potential of interventional treatment. In spite of much progress in coronary stents, little is towards peripheral stents, which are expected to be both long and biodegradable and thus require a breakthrough in core techniques. Herein, we develop a long and biodegradable stent with a length of up to 118 mm based on a metal-polymer composite material. To achieve a well-prepared homogeneous coating on a long stent during ultrasonic spraying, a magnetic levitation is employed. In vivo degradation of the stent is investigated in rabbit abdominal aorta/iliac arteries, and its preclinical safety is evaluated in canine infrapopliteal arteries. First-in-man implantation of the stent is carried out in the below-the-knee artery. The 13 months' follow-ups demonstrate the feasibility of the long and biodegradable stent in clinical applications.

Effects of serum proteins on corrosion rates and product bioabsorbability of biodegradable metals.

Corrodible metals are the newest kind of biodegradable materials and raise a new problem of the corrosion products. However, the removal of the precipitated products has been unclear and even largely ignored in publications. Herein, we find that albumin, an abundant macromolecule in serum, enhances the solubility of corrosion products of iron in blood mimetic Hank's solution significantly. This is universal for other main biodegradable metals such as magnesium, zinc and polyester-coated iron. Albumin also influences corrosion rates in diverse trends in Hank's solution and normal saline. Based on quantitative study theoretically and experimentally, both the effects on corrosion rates and soluble fractions are interpreted by a unified mechanism, and the key factor leading to different corrosion behaviors in corrosion media is the interference of albumin to the Ca/P passivation layer on the metal surface. This work has illustrated that the interactions between metals and media macromolecules should be taken into consideration in the design of the next-generation metal-based biodegradable medical devices in the formulism of precision medicine. The improved Hank's solution in the presence of albumin and with a higher content of initial calcium salt is suggested to access biodegradable metals potentially for cardiovascular medical devices, where the content of calcium salt is calculated after consideration of chelating of calcium ions by albumin, resulting in the physiological concentration of free calcium ions.

Mixed ensiling plus nitrate destroy fiber structure of rape straw, increase degradation, and reduce methanogenesis through in vitro ruminal fermentation.

BACKGROUND: Better utilization of rape straw can provide alternative strategies for sustainable ruminant and food production. The research reported here investigated changes in the carbohydrate composition of rape straw as a result of mixed ensiling with whole-crop corn or inoculated with nitrate, and the consequent effects on ruminal fermentation through in vitro batch culture. The three treatments included: rape straw and corn silage (RSTC), and ensiling treatment of rape straw with whole-crop corn (RSIC) or with calcium nitrate inoculation (RSICN). RESULTS: Ensiling treatment of rape straw and whole-crop corn or plus nitrate enriched lactic acid bacteria and lactate. The treatments broke the fiber surface connections of rape straw, leading to higher neutral detergent soluble (NDS) content and lower fiber content. Ensiling treatments led to greater (P < 0.05) dry matter degradation (DMD), molar proportions of propionate and butyrate, relative abundance of the phylum Bacteroidetes and genus Prevotella, and lower (P < 0.05) methane production in terms of g kg-1 DMD, molar proportions of acetate, and lower acetate to propionate ratio than the RSTC treatment. The RSICN treatment led to the lowest (P < 0.05) hydrogen concentration and methane production among the three treatments. CONCLUSION: Ensiling treatments of rape straw and whole-crop corn destroy the micro-structure of rape straw, promote substrate degradation by enriching the phylum Bacteroidetes and the genus Prevotella, and decrease methane production by favoring propionate and butyrate production. Nitrate inoculation in the ensiling treatment of rape straw and whole-crop corn further decreases methane production without influencing substrate degradation by providing an additional hydrogen sink. © 2023 Society of Chemical Industry.

Effect of mindfulness-based mind-body therapies in patients with non-specific low back pain-A network meta-analysis of randomized controlled trials.

Background/objectives: Although mindfulness-based mind-body therapy (MBMBT) is an effective non-surgical treatment for patients with non-specific low back pain (NLBP), the best MBMBT mode of treatment for NLBP patients has not been identified. Therefore, a network meta-analysis (NMA) was conducted to compare the effects of different MBMBTs in the treatment of NLBP patients. Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for randomized controlled trials (RCTs) applying MBMBT for the treatment of NLBP patients, with all of the searches ranging from the time of database creation to January 2023. After 2 researchers independently screened the literature, extracted information, and evaluated the risks of biases in the included studies, the data were analyzed by using Stata 16.0 software. Results: A total of 46 RCTs were included, including 3,886 NLBP patients and 9 MBMBT (Yoga, Ayurvedic Massage, Pilates, Craniosacral Therapy, Meditation, Meditation + Yoga, Qigong, Tai Chi, and Dance). The results of the NMA showed that Craniosacral Therapy [surface under the cumulative ranking (SUCRA): 99.2 and 99.5%] ranked the highest in terms of improving pain and disability, followed by Other Manipulations (SUCRA: 80.6 and 90.8%) and Pilates (SUCRA: 54.5 and 71.2%). In terms of improving physical health, Craniosacral Therapy (SUCRA: 100%) ranked the highest, followed by Pilates (SUCRA: 72.3%) and Meditation (SUCRA: 55.9%). In terms of improving mental health, Craniosacral Therapy (SUCRA: 100%) ranked the highest, followed by Meditation (SUCRA: 70.7%) and Pilates (SUCRA: 63.2%). However, in terms of improving pain, physical health, and mental health, Usual Care (SUCRA: 7.0, 14.2, and 11.8%, respectively) ranked lowest. Moreover, in terms of improving disability, Dance (SUCRA: 11.3%) ranked lowest. Conclusion: This NMA shows that Craniosacral Therapy may be the most effective MBMBT in treating NLBP patients and deserves to be promoted for clinical use. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO [CRD42023389369].

Sarcopenia negatively affects postoperative short-term outcomes of patients with non-cirrhosis liver cancer.

BACKGROUND: Literature review have shown that sarcopenia substantially alters the postoperative outcomes after liver resection for malignant tumors. However, these retrospective studies do not distinguish cirrhotic and non-cirrhotic liver cancer patients, nor combine the assessment of muscle strength in addition to muscle mass. The purpose of this study is to study the relationship between sarcopenia and short-term outcomes after hepatectomy in patients with non-cirrhotic liver cancer. METHODS: From December 2020 to October 2021, 431 consecutive inpatients were prospectively enrolled in this study. Muscle strength and mass were assessed by handgrip strength and the skeletal muscle index (SMI) on preoperative computed tomographic scans, respectively. Based on the SMI and the handgrip strength, patients were divided into four groups: group A (low muscle mass and strength), group B (low muscle mass and normal muscle strength), group C (low muscle strength and normal muscle mass), and group D (normal muscle mass and strength). The main outcome was major complications and the secondary outcome was 90-d Readmission rate. RESULTS: After strictly exclusion, 171 non-cirrhosis patients (median age, 59.00 [IQR, 50.00-67.00] years; 72 females [42.1%]) were selected in the final analysis. Patients in group A had a statistically significantly higher incidence of major postoperative complications (Clavien-Dindo classification ≥ III) (26.1%, p = 0.032), blood transfusion rate (65.2%, p < 0.001), 90-day readmission rate (21.7%, p = 0.037) and hospitalization expenses (60,842.00 [IQR, 35,563.10-87,575.30], p < 0.001) than other groups. Sarcopenia (hazard ratio, 4.21; 95% CI, 1.44-9.48; p = 0.025) and open approach (hazard ratio, 2.56; 95% CI, 1.01-6.49; p = 0.004) were independent risk factors associated with major postoperative complications. CONCLUSIONS: Sarcopenia is closely related to poor short-term postoperative outcomes in non-cirrhosis liver cancer patients and the assessment that combines muscle strength and muscle mass can simply and comprehensively identify it. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT04637048 . (19/11/2020).

The Black-Box Deconstruction of Dynamic Sustainable Development Ability Driving Environmental Performance of Manufacturing Enterprises.

Based on the conceptual model of the black-box deconstruction of dynamic sustainable development ability driving environmental performance of manufacturing enterprises, the nonparametric percentile bootstrap method based on deviation correction is used to demonstrate the theoretical hypothesis and empirically deconstruct the black-box of dynamic sustainable development driving environmental performance. Empirical results show that (1) dynamic sustainable development ability has a positive influence on environmental performance; (2) green resource integration ability, green duality, low-carbon manufacturing practice, and green intelligence capital play mediating roles in the influence of dynamic sustainable development ability on environmental performance; and (3) environmental regulation positively moderates the mediating mechanism of green resource integration ability, green duality, low-carbon manufacturing practice, and green intelligence capital of the relationships between dynamic sustainable development ability and environmental performance.

A Biodegradable Metal-Polymer Composite Stent Safe and Effective on Physiological and Serum-Containing Biomimetic Conditions.

The new-generation coronary stents are expected to be biodegradable, and then the biocompatibility along with biodegradation becomes more challenging. It is a critical issue to choose appropriate biomimetic conditions to evaluate biocompatibility. Compared with other candidates for biodegradable stents, iron-based materials are of high mechanical strength, yet have raised more concerns about biodegradability and biocompatibility. Herein, a metal-polymer composite strategy is applied to accelerate the degradation of iron-based stents in vitro and in a porcine model. Furthermore, it is found that serum, the main environment of vascular stents, ensured the safety of iron corrosion through its antioxidants. This work highlights the importance of serum, particularly albumin, for an in vitro condition mimicking blood-related physiological condition, when reactive oxygen species, inflammatory response, and neointimal hyperplasia are concerned. The resultant metal-polymer composite stent is implanted into a patient in clinical research via interventional treatment, and the follow-up confirms its safety, efficacy, and appropriate biodegradability.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

Surface modification to enhance cell migration on biomaterials and its combination with 3D structural design of occluders to improve interventional treatment of heart diseases.

The dominant source of thromboembolism in heart comes from the left atrial appendage (LAA). An occluder can close LAA and significantly reduce the risk of strokes, particularly for those patients with atrial fibrillation. However, it is technically challenging to fabricate an LAA occluder that is appropriate for percutaneous implantation and can be rapidly endothelialized to accomplish complete closure and avoid severe complication. Hypothesizing that a fast migration rate of endothelial cells on the implant surface would lead to rapid endothelialization, we fabricated an LAA occlusion device for interventional treatment with a well-designed 3D architecture and a nanoscale 2D coating. Through screening of biomaterials surfaces with cellular studies in vitro including cell observations, qPCR, RNA sequencing, and implantation studies in vivo, we revealed that a titanium-nitrogen nanocoating on a NiTi alloy promoted high migration rate of endothelial cells on the surface. The effectiveness of this first nanocoating LAA occluder was validated in animal experiments and a patient case, both of which exhibited successful implantation, fast sealing and long-term safety of the device. The mechanistic insights gained in this study will be useful for the design of medical devices with appropriate surface modification, not necessarily for improved cell adhesion but sometimes for enhanced cell migration.

PDLLA-Zn-nitrided Fe bioresorbable scaffold with 53-µm-thick metallic struts and tunable multistage biodegradation function.

Balancing the biodegradability and mechanical integrity of a bioresorbable scaffold (BRS) with time after implantation to match the remodeling of the scaffolded blood vessel is important, but a key challenge in doing so remains. This study presents a novel intercalated structure of a metallic BRS by introducing a nanoscale Zn sacrificial layer between the nitrided Fe platform and the sirolimus-carrying poly(d,l-lactide) drug coating. The PDLLA-Zn-FeN BRS shows a multistage biodegradation behavior, maintaining mechanical integrity at the initial stage and exhibiting accelerated biodegradation at the subsequent stage in both rabbit abdominal aortas and human coronary arteries, where complete biodegradation was observed about 2 years after implantation. The presence of the nanoscale Zn sacrificial layer with an adjustable thickness also contributes to the tunable biodegradation of BRS and allows the reduction of the metallic strut thickness to 53 µm, with radial strength as strong as that of the current permanent drug-eluting stents.

In vivo degradation and endothelialization of an iron bioresorbable scaffold.

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds (BRSs). In particular, it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments; otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial. Herein, we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold (IBS) based on optical coherence tomography (OCT) images; this approach was confirmed to be consistent with the present weight-loss measurements, which is, however, a destructive approach. The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent. The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience, which has been widely used in clinic. The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model; and our well-designed ultrathin stent exhibited less individual variation. We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models. The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model. The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.

Outcomes of Discectomy by Using Full-Endoscopic Visualization Technique via the Transcorporeal and Transdiscal Approaches in the Treatment of Cervical Intervertebral Disc Herniation: A Comparative Study.

OBJECTIVE: To compare the difference in clinical and radiographic outcomes between anterior transcorporeal and transdiscal percutaneous endoscopic cervical discectomy (ATc-PECD/ATd-PECD) approaches for treating patients with cervical intervertebral disc herniation (CIVDH). METHOD: We selected 77 patients with single-segment CIVDH and received ATc-PECD or ATd-PECD in the Second Affiliated Hospital of Chongqing Medical University between March 1, 2010, and July 1, 2015. 35 patients suffered from ATc-PECD, and there were 42 patients in the ATd-PECD group. Obtaining the data of 1, 3, 6, 12, and 24 months postoperatively, the VAS for neck and arm pain and the modified MacNab criteria were used to evaluate the clinical outcomes, comparing radiographic outcomes and complications of these two groups. RESULTS: We found that the mean operative time was significantly longer in the ATc-PECD group (P < 0.05). At the 2-year follow-up, the mean VAS score for neck and arm pain was significantly decreased in both two groups. There was no significant difference in the VAS score for arm pain and neck pain between the two groups at the 2-year follow-up (P=0.783 and P=0.785, respectively). For the ATc-PECD group, the difference in the height of IVS or vertebral body was significant between the preoperative and postoperative groups (P < 0.05, respectively). For the ATd-PECD group, there was only a significant decrease in the height of the IVS (P < 0.05); the decrease in the surgical vertebral body was not significant between the preoperative and postoperative groups (P > 0.05). CONCLUSION: In the 2-year follow-up, there is no significant difference in the clinical outcomes between the 2 approaches. While the longer time was consumed in the ATc-PECD group, the lower rate of disc collapse and recurrence is notable. Additionally, when the center diameter of tunnel was limited to 6 mm, the bony defect can be healed without the occurrence of the collapse of the superior endplate, and ATc-PECD may be preferable in the endoscopic treatment of CIVDH.

Long-Term Efficacy of Biodegradable Metal-Polymer Composite Stents After the First and the Second Implantations into Porcine Coronary Arteries.

A biodegradable coronary stent is expected to eliminate the adverse events of an otherwise eternally implanting material after vessel remodeling. Both biocorrodible metals and biodegradable polymers have been tried as the matrix of the new-generation stent. Herein, we utilized a metal-polymer composite material to combine the advantages of the high mechanical strength of metals and the adjustable degradation rate of polymers to prepare the biodegradable stent. After coating polylactide (PLA) on the surface of iron, the degradation of iron was accelerated significantly owing to the decrease of local pH resulting from the hydrolysis of PLA, etc. We implanted the metal-polymer composite stent (MPS) into the porcine artery and examined its degradation in vivo, with the corresponding metal-based stent (MBS) as a control. Microcomputed tomography (micro-CT), coronary angiography (CA), and optical coherence tomography (OCT) were performed to observe the stents and vessels during the animal experiments. The MPS exhibited faster degradation than MBS, and the inflammatory response of MPS was acceptable 12 months after implantation. Additionally, we implanted another MPS after 1-year implantation of the first MPS to investigate the result of the MPS in the second implantation. The feasibility of the biodegradable MPS in second implantation in mammals was also confirmed.

Characterization and in vivo evaluation of a bio-corrodible nitrided iron stent.

A bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique. In the nitrided iron stents, the tensile strength, radial strength, stiffness and in vitro electrochemical corrosion rate were significantly increased compared with those of the control pure iron stent. To evaluate its performance in vivo, the deployment of the nitrided iron stents in juvenile pig iliac arteries was performed. At 3 or 6 months postoperatively, the stented vessels remained patent well; however, slight luminal loss resulting from intimal hyperplasia and relative stenosis of the stented vessel segment with piglets growth were observed by 12 months; no thrombosis or local tissue necrosis was found. At 1 month postoperatively, a nearly intact layer of endothelial cells formed on the stented vessel wall. Additionally, a decreased inflammation scoring, considerably corroded struts and corrosion products accumulation were seen. These findings indicate the potential of this nitrided iron stent as an attractive biodegradable stent.