Fabrication and properties of PLA/ß-TCP scaffolds using liquid crystal display (LCD) photocuring 3D printing for bone tissue engineering.

Introduction: Bone defects remain a thorny challenge that clinicians have to face. At present, scaffolds prepared by 3D printing are increasingly used in the field of bone tissue repair. Polylactic acid (PLA) has good thermoplasticity, processability, biocompatibility, and biodegradability, but the PLA is brittle and has poor osteogenic performance. Beta-tricalcium phosphate (ß-TCP) has good mechanical properties and osteogenic induction properties, which can make up for the drawbacks of PLA. Methods: In this study, photocurable biodegradable polylactic acid (bio-PLA) was utilized as the raw material to prepare PLA/ß-TCP slurries with varying ß-TCP contents (ß-TCP dosage at 0%, 10%, 20%, 30%, 35% of the PLA dosage, respectively). The PLA/ß-TCP scaffolds were fabricated using liquid crystal display (LCD) light-curing 3D printing technology. The characterization of the scaffolds was assessed, and the biological activity of the scaffold with the optimal compressive strength was evaluated. The biocompatibility of the scaffold was assessed through CCK-8 assays, hemocompatibility assay and live-dead staining experiments. The osteogenic differentiation capacity of the scaffold on MC3T3-E1 cells was evaluated through alizarin red staining, alkaline phosphatase (ALP) detection, immunofluorescence experiments, and RT-qPCR assays. Results: The prepared scaffold possesses a three-dimensional network structure, and with an increase in the quantity of ß-TCP, more ß-TCP particles adhere to the scaffold surface. The compressive strength of PLA/ß-TCP scaffolds exhibits a trend of initial increase followed by decrease with an increasing amount of ß-TCP, reaching a maximum value of 52.1 MPa at a 10% ß-TCP content. Degradation rate curve results indicate that with the passage of time, the degradation rate of the scaffold gradually increases, and the pH of the scaffold during degradation shows an alkaline tendency. Additionally, Live/dead staining and blood compatibility experiments suggest that the prepared PLA/ß-TCP scaffold demonstrates excellent biocompatibility. CCK-8 experiments indicate that the PLA/ß-TCP group promotes cell proliferation, and the prepared PLA/ß-TCP scaffold exhibits a significant ability to enhance the osteogenic differentiation of MC3T3-E1 cells in vitro. Discussion: 3D printed LCD photocuring PLA/ß-TCP scaffolds could improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy for developing bioactive implants in orthopedic applications.

A novel lncRNA SNHG29 regulates EP300- related histone acetylation modification and inhibits FLT3-ITD AML development.

Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) occur in up to 25% of acute myeloid leukemia (AML) patients and indicate a very poor prognosis. The role of long noncoding RNAs (lncRNAs) in FLT3-ITD AML progression remains unexplored. We identified a novel lncRNA, SNHG29, whose expression is specifically regulated by the FLT3-STAT5 signaling pathway and is abnormally down-regulated in FLT3-ITD AML cell lines. SNHG29 functions as a tumor suppressor, significantly inhibiting FLT3-ITD AML cell proliferation and decreasing sensitivity to cytarabine in vitro and in vivo models. Mechanistically, we demonstrated that SNHG29's molecular mechanism is EP300-binding dependent and identified the EP300-interacting region of SNHG29. SNHG29 modulates genome-wide EP300 genomic binding, affecting EP300-mediated histone modification and consequently influencing the expression of varies downstream AML-associated genes. Our study uncovers a novel molecular mechanism for SNHG29 in mediating FLT3-ITD AML biological behaviors through epigenetic modification, suggesting that SNHG29 could be a potential therapeutic target for FLT3-ITD AML.

Copper-containing chitosan-based hydrogels enabled 3D-printed scaffolds to accelerate bone repair and eliminate MRSA-related infection.

Bone defect combined with drug-resistant bacteria-related infection is a thorny challenge in clinic. Herein, 3D-printed polyhydroxyalkanoates/ß-tricalcium phosphate (PHA/ß-TCP, PT) scaffolds were prepared by fused deposition modeling. Then copper-containing carboxymethyl chitosan/alginate (CA/Cu) hydrogels were integrated with the scaffolds via a facile and low-cost chemical crosslinking method. The resultant PT/CA/Cu scaffolds could promote not only proliferation but also osteogenic differentiation of preosteoblasts in vitro. Moreover, PT/CA/Cu scaffolds exhibited a strong antibacterial activity towards a broad-spectrum of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) through inducing the intercellular generation of reactive oxygen species. In vivo experiments further demonstrated that PT/CA/Cu scaffolds significantly accelerated bone repair of cranial defects and efficiently eliminated MRSA-related infection, showing potential for application in infected bone defect therapy.

Carboxymethyl chitosan/sodium alginate hydrogels with polydopamine coatings as promising dressings for eliminating biofilm and multidrug-resistant bacteria induced wound healing.

Microorganisms induced wound infection and the accompanying excessive inflammatory response is the daunting problems in wound treatment. Due to the lack of corresponding biological functions, traditional wound dressings cannot effectively protect the wound and are prone to induce local infection, excessive inflammation, and vascular damage, resulting in prolonged unhealing. Here, a mussel-inspired strategy was adopted to prepare a multifunctional hydrogel created by H2O2/CuSO4-induced rapid polydopamine (PDA) deposition on carboxymethyl chitosan (CMC)/sodium alginate (Alg) based hydrogel, termed as CAC/PDA/Cu(H2O2). The prepared CAC/PDA/Cu(H2O2) hydrogel features excellent biocompatibility, adequate mechanical properties, and good degradability. Moreover, the CAC/PDA/Cu(H2O2) hydrogel can not only realize antibacterial, and anti-inflammatory effects, but also promote angiogenesis to accelerate wound healing in vitro thanks to the composite PDA/Cu(H2O2) coatings. Significantly, CAC/PDA/Cu(H2O2) hydrogel illustrates excellent therapeutic effects in Methicillin-resistant Staphylococcus aureus (MRSA) induced-rat infection models, which can efficiently eliminate MRSA, dramatically reduce inflammatory expression, promote angiogenesis, and ultimately shorten the wound healing time. CAC/PDA/Cu(H2O2) hydrogel exhibited the best wound healing rate on days 7 (80.63 ± 2.44 %), 11 (92.45 ± 2.26 %), and 14 (97.86 ± 0.66 %). Thus, the multifunctional hydrogel provides a facile and efficient approach to wound management and represents promising potential in the therapy for wound healing.

Asymmetries and relationships between muscle strength, proprioception, biomechanics, and postural stability in patients with unilateral knee osteoarthritis.

Background: The pathological mechanism of knee osteoarthritis (KOA) is unknown. KOA degeneration may be associated with changes in muscle strength, proprioception, biomechanics, and postural stability. Objective: This study aimed to assess asymmetries in muscle strength, proprioception, biomechanics, and postural stability of bilateral lower limbs in patients with unilateral KOA and healthy controls and analyze correlations between KOA and these parameters. Methods: A total of 50 patients with unilateral KOA (age range: 50-70) and 50 healthy subjects were recruited as study participants (age range: 50-70). Muscle strength, proprioception, femorotibial angle (FTA), femoral condylar-tibial plateau angle (FCTP), average trajectory error (ATE), and center of pressure (COP) sways areas were accessed in study participants, and the correlation between these variables was investigated. Results: In patients with unilateral KOA, lower limb muscle strength was significantly lower on the symptomatic side than on the asymptomatic side (p < 0.01), while the proprioception (degree error), FTA, FCTP, and ATE were substantially higher compared to the asymptomatic side (p < 0.01). However, no significant difference was observed in the healthy controls (p > 0.05). Patients with unilateral KOA had lower muscle strength than healthy controls (p < 0.05), but their proprioception (degree error: the difference between the target and reproduction angles), ATE, and COP sway areas were higher (p < 0.05). Muscle strength was found to be negatively correlated with ATE and COP sways areas (p < 0.05), whereas proprioception (degree error) was positively correlated with ATE and COP sways areas (p < 0.05) in all study participants. However, no correlation was found between FTA, FCTP, and ATE, COP sways areas in patients with unilateral KOA (p > 0.05). Conclusion: In patients with unilateral KOA, muscle strength, proprioception, biomechanics, and postural stability of bilateral limbs are asymmetrical in unilateral KOA patients. Muscle strength, proprioception, and postural stability are significantly associated variables, and changes in these variables should be considered in KOA prevention and rehabilitation.

Nano tantalum-coated 3D printed porous polylactic acid/beta-tricalcium phosphate scaffolds with enhanced biological properties for guided bone regeneration.

Bone defects caused by tumors section, traffic accidents, and surgery remain a challenge in clinical. The drawbacks of traditional autografts and allografts limit their clinical application. 3D printed porous scaffolds have monumental potential to repair bone defects but still cannot effectively promote bone formation. Nano tantalum (Ta) has been reported with effective osteogenesis capability. Herein, we fabricated 3D printed PLA/ß-TCP scaffold by using the fused deposition modeling (FDM) technique. Ta was doped on the surface of scaffolds utilizing the surface adhesion ability of polydopamine to improve its properties. The constructed PLA/ß-TCP/PDA/Ta had good physical properties. In vitro studies demonstrated that the PLA/ß-TCP/PDA/Ta scaffolds considerably promote cell proliferation and migration, and it additionally has osteogenic properties. Therefore, Ta doped 3D printed PLA/ß-TCP/PDA/Ta scaffold could incontestably improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy to develop bioactive bespoke implants in orthopedic applications.

Customized Design 3D Printed PLGA/Calcium Sulfate Scaffold Enhances Mechanical and Biological Properties for Bone Regeneration.

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Beta-tricalcium phosphate enhanced mechanical and biological properties of 3D-printed polyhydroxyalkanoates scaffold for bone tissue engineering.

Polyhydroxyalkanoates (PHA) is a naturally degradable polyester with good biocompatibility. However, several disadvantages including poor bioactivity and mechanical properties limit the biomedical application of PHA. To circumvent these drawbacks, PHA needs to be blended with other materials to improve performance. Beta-tricalcium phosphate (ß-TCP) has emerged as one of the most promising bone repair materials due to its good biocompatibility, satisfactory mechanical properties, and excellent bone osteoconductivity. In this study, PHA filled with ß-TCP in 0 wt%, 5 wt%, 10 wt%, 20 wt%, and 30 wt% of concentrations were produced using a twin-screw extruder. The extruded 3D filaments made with 20% ß-TCP exhibited the maximum mechanical properties to manufacture 3D scaffolds for bone tissue engineering. We then prepared the 3D-printed PHA/ß-TCP scaffolds by using the fused deposition modeling (FDM) technique. The compressive strength and the shore hardness of the PHA/20%ß-TCP scaffold were 36.7 MPa and 81.1 HD. The produced scaffolds presented compressive strength compatible with natural bone. In addition, the scaffolds with a well-controlled design of pore shape and size provided sufficient space for cellular activity. In vitro studies demonstrated that the addition of ß-TCP could significantly improve the proliferation, adhesion, and migration of MC3T3-E1 cells in the PHA/ß-TCP scaffold. Moreover, the osteogenesis-related genes expression of the PHA/ß-TCP scaffold was enhanced compared to the PHA scaffolds. Therefore, the 3D-printed PHA/ß-TCP scaffold represents an effective strategy to promote mechanical and biological properties, showing huge potential for bone tissue engineering applications.

The Effects of Patient Education on Psychological Status and Clinical Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Background: Rheumatoid arthritis (RA) is a common systemic inflammatory autoimmune disease. The disease has a serious impact on mental health and requires more effective non-pharmacological interventions. Objective: This study aims to systematically evaluate the effectiveness of patient education on psychological status and clinical outcomes in rheumatoid arthritis. Methods: This systematic review and meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Cochrane Library, EMBASE database, and Web of Science database were screened for articles published until November 2, 2021. Randomized controlled trials (RCTs) of patient education for RA were included. Outcomes measures included pain, physical function, disease activity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anxiety, depression, Arthritis Self-Efficacy (pain, other symptoms, total), and General health. For each outcome, standardized mean differences or mean differences and 95% confidence intervals (CIs) were calculated. Results: A total of 24 RCTs (n = 2,276) were included according to the inclusion and exclusion criteria. Meta-analysis revealed a statistically significant overall effect in favor of patient education for physical function [SMD = -0.52, 95% CI (-0.96, -0.08), I 2 = 93%, P = 0.02], disease activity [SMD = -1.97, 95% CI (-3.24, -0.71), I 2 = 97%, P = 0.002], ASE (pain) [SMD = -1.24, 95% CI (-2.05, -0.43), I 2 = 95%, P = 0.003], ASE (other symptoms) [SMD = -0.25, 95% CI (-0.41, -0.09), I 2 = 25%, P = 0.002], ASE (total) [SMD = -0.67, 95% CI (-1.30, -0.05), I 2 = 90%, P = 0.03], and general health [SMD = -1.11, 95% CI (-1.36, -0.86), I 2 = 96%, P < 0.00001]. No effects were found for anxiety [SMD = 0.17, 95% CI (-0.64, 0.98), I 2 = 82%, P = 0.68], depression [SMD = -0.18, 95% CI (-0.52, 0.15), I 2 = 52%, P = 0.28], pain [SMD = -0.37, 95% CI (-0.80, 0.05), I 2 = 89%, P = 0.08], and CRP [SMD = -0.27, 95% CI (-0.57, 0.02), I 2 = 0%, P = 0.07]. Conclusions: Patient education may be effective in improving clinical outcomes and psychological status in patients with rheumatoid arthritis. Considering the methodological limitations of the included RCTs, more high-quality and large-sample RCTs are needed to confirm this conclusion in the future. Systematic Review Registration: http://www.crd.york.ac.uk/prospero, identifier: CRD42021250607.

Asymmetric Biomechanical Properties of the Paravertebral Muscle in Elderly Patients With Unilateral Chronic Low Back Pain: A Preliminary Study.

Background: Clinical incidences of chronic low back pain among the elderly are increasing. However, studies have not fully elucidated on changes in biomechanical properties of paravertebral muscles in patients with unilateral chronic low back pain. We evaluated the changes in biomechanical properties of painful and non-painful paravertebral muscles in elderly patients with unilateral chronic low back pain. Methods: Biomechanical properties of paravertebral muscles, including muscle tone and stiffness, in elderly patients with unilateral chronic low back pain were measured using MyotonPRO. Lumbar Lordosis and Sacral Slope were measured by magnetic resonance imaging. Cross-sectional areas of paravertebral muscles were evaluated using ImageJ software version 1.53. Chronic low back pain severity was assessed by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores. The correlations between VAS scores, ODI scores, Lumbar Lordosis, Sacral Slope, cross-sectional areas (painful side), disease duration, and biomechanical properties of paravertebral muscles in the painful side were analyzed. Results: A total of 60 elderly patients with unilateral chronic low back pain were enrolled in this study. The muscle tone and stiffness of paravertebral muscles on the painful side were significantly higher than those on the non-painful side (p < .05). Cross-sectional areas of paravertebral muscles on the painful side at the L3 level were smaller than those of the non-painful side (p < .05). The VAS scores and ODI scores were significantly positively correlated with muscle tone and stiffness of paravertebral muscles on the painful side (p < .05 and p < .01, respectively). There were no significant correlations between disease duration, cross-sectional areas (painful side), Lumbar Lordosis, or Sacral Slope and muscle tone and stiffness of paravertebral muscles on the painful side (p > .05). Conclusion: In elderly patients with unilateral chronic low back pain, muscle tone and stiffness of paravertebral muscles on the painful side are higher than for those on the non-painful side. The asymmetry of biomechanical properties of paravertebral muscles is associated with severity of chronic low back pain.

Proprioceptive Training for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: There is increased interest in proprioceptive training for knee osteoarthritis (KOA). However, little consensus supports the effectiveness of this intervention. Objective: This meta-analysis aimed to assess the effects of proprioceptive training on symptoms, function, and proprioception in people with KOA. Methods: The PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically searched from the inception dates to April 16, 2021 for relevant randomized controlled trials (RCTs). Data were pooled by calculating the standardized mean differences (SMDs) and 95% confidence intervals (CIs). A random-effects model was used for the analyses. Results: A total of 24 RCTs involving 1,275 participants were included in our analysis. This study indicated that compared to no intervention, proprioceptive training significantly improved pain, stiffness, physical function, joint position sense (JPS), muscle strength, mobility, and knee ROM (P < 0.05) in people with KOA. When compared to other non-proprioceptive training, proprioceptive training provided better results in terms of JPS (SMD = -1.28, 95%CI: [-1.64, -0.92], I 2 = 0%, P < 0.00001) and mobility (timed walk over spongy surface) (SMD = -0.76, 95%CI: [-1.33, -0.18], I 2 = 64%, P = 0.01), and other results are similar. When proprioceptive training plus other non-proprioceptive training compared to other non-proprioceptive training, the two groups showed similar outcomes, but there was a greater improvement for JPS (SMD = -1.54, 95%CI: [-2.74, -0.34], I 2 = 79%, P = 0.01), physical function (SMD = -0.34, 95%CI: [-0.56, -0.12], I 2 = 0%, P = 0.003), and knee ROM (P < 0.05) in the proprioceptive training plus other non-proprioceptive training group. When proprioceptive training plus conventional physiotherapy compared against conventional physiotherapy, the two groups demonstrated similar outcomes, but there was a significant improvement for JPS (SMD = -0.95, 95%CI: [-1.73, -0.18], I 2 = 78%, P = 0.02) in the proprioceptive training plus conventional physiotherapy group. Conclusions: Proprioceptive training is safe and effective in treating KOA. There is some evidence that proprioceptive training combined with general non-proprioceptive training or conventional physiotherapy appears to be more effective and should be considered as part of the rehabilitation program. However, given that the majority of current studies investigated the short-term effect of these proprioceptive training programs, more large-scale and well-designed studies with long-term follow up are needed to determine the long-term effects of these proprioceptive training regimes in KOA. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, PROSPERO, identifier: CRD42021240587.

Comparison of the Asymmetries in Foot Posture and Properties of Gastrocnemius Muscle and Achilles Tendon Between Patients With Unilateral and Bilateral Knee Osteoarthritis.

Background: Asymmetrical foot posture and properties alterations of the gastrocnemius muscle (GM) and Achilles tendon (AT) were observed in knee osteoarthritis (KOA). We aimed to investigate the inter-limbs asymmetries in foot posture and the properties of GM and AT and explore the association between them. Methods: A total of 62 subjects with unilateral or bilateral KOA were included in this study: 30 patients with unilateral pain and 32 patients with bilateral pain were assigned to the bilateral group (BG) and unilateral group (UG), respectively. The relatively serious leg (RSL) and relatively moderate leg (RML) were judged according to the severity of symptoms assessed by using visual analogue scale (VAS) motion. Foot posture and asymmetrical foot posture scores were assessed based on Foot Posture index (FPI-6). Subsequently, all the participants received an assessment for properties of GM and AT, including tone/tension (Hz), stiffness (N/m), and elasticity. We calculated the asymmetry index of AT (Asy -AT) in both legs and the difference of muscle properties between medial and lateral gastrocnemius (D-MLG) in the ipsilateral limb. Results: Asymmetry of foot posture was categorized into three types including normal, asymmetry, and severe asymmetry. The percentage of subjects classified as normal was higher in the BG (62.5%) than in the UG (36.67%), p < 0.05. Tension of AT and tone of lateral gastrocnemius (LG) in RSL were higher than those in RML (15.71 ± 0.91 vs. 15.23 ± 1.01; 25.31 ± 2.09 vs. 23.96 ± 2.08, p < 0.01 and p < 0.01, respectively), and stiffness of AT in the RSL was higher than that in RML (676.58 ± 111.45 vs. 625.66 ± 111.19, p < 0.01). Meanwhile, a positive relationship was found between ipsilateral FPI and tone of MG and LG in the left leg (0.246 per degree, 95% CI: -0.001, 0.129; p = 0.054 and 0.293 per degree, 95% CI: -0.014, 0.157; p = 0.021, respectively) and right leg (0.363 per degree, 95% CI: 0.033, 0.146; p = 0.004 and 0.272 per degree, 95% CI: 0.007, -0.144; p = 0.032, respectively). Moreover, a positive link was observed between asymmetrical FPI scores and K/L grade (0.291 per degree, 95% CI: 0.018, 0.216; p = 0.022). Furthermore, a significantly greater Asy-AT(tension) was detected in the UG than that in the BG (UG vs. UG: 8.20 ± 5.09% vs. 5.11 ± 4.72%, p < 0.01). Additionally, an increased asymmetrical FPI score (i.e., more severe asymmetry) was significantly associated with increases in Asy-AT(tension) and Asy-AT(stiffness) (0.42 per degree, 95% CI: 0.533, 1.881; p = 0.001 and 0.369 per degree, 95% CI: 0.596, 2.82; p = 0.003, respectively). Conclusions: The stiffness and tension of AT and the tone of LG in RSL were higher than those in RML in KOA patients, and inter-limbs foot posture and tension of AT were more asymmetrical in unilateral KOA patients compared to patients with bilateral KOA. Notably, foot posture, as an important biomechanical factor, was significantly associated with properties of GM, AT, and K/L grade in KOA patients.

Effects of Age and Sex on Properties of Lumbar Erector Spinae in Healthy People: Preliminary Results From a Pilot Study.

Background: The influences of age and sex on properties of lumbar erector spinae have not been previously studied. Changes in the performance of lumbar erector spinae properties associated with age represent a valuable indicator of risk for lower-back-related disease. Objective: To investigate the lumbar erector spinae properties with regard to age and sex to provide a reference dataset. Methods: We measured muscle tone and stiffness of the lumbar erector spinae (at the L3-4 level) in healthy men and women (50 young people, aged 20-30 years; 50 middle-aged people, aged 40-50 years; and 50 elderly people, aged 65-75 years) using a MyotonPRO device. Results: In general, there are significant differences in muscle tone and stiffness among young, middle-aged, and elderly participants, and there were significant differences in muscle tone and stiffness between men and women, and there was no interaction between age and sex. The muscle tone and stiffness of the elderly participants were significantly higher than those of the middle-aged and young participants (P < 0.01), and the muscle tone and stiffness of the middle-aged participants were significantly higher than those of the young participants (P < 0.01). In addition, the muscle tone and stiffness of men participants were significantly higher than that of women participants (P < 0.01). Conclusion: Our results indicate that muscle tone and stiffness of the lumbar erector spinae increase with age. The muscle tone and stiffness of the lumbar erector spinae in men are significantly higher than in women. The present study highlights the importance of considering age and sex differences when assessing muscle characteristics of healthy people or patients.

Biodegradable mesoporous manganese carbonate nanocomposites for LED light-driven cancer therapy via enhancing photodynamic therapy and attenuating survivin expression.

Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2 and CO2 under H2O2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.

Myofascial Release for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Background: Chronic low back pain (CLBP) is one of the most common musculoskeletal diseases in the elderly, which has a severe impact on the health of the elderly. However, CLBP treatment is very challenging, and more effective treatment methods are needed. Myofascial release may be an effective therapy for the management of chronic musculoskeletal pain. It is widely used clinically to treat CLBP, but its clinical efficacy is still controversial. Objective: This study aims to systematically evaluate the effectiveness of myofascial release for patients with CLBP. Methods: We selected PubMed, Cochrane Library, EMBASE database, and Web of Science database articles published until April 5, 2021. Randomized controlled trials (RCTs) of myofascial release for CLBP were included. Outcome measures included pain, physical function, quality of life, balance function, pain pressure-threshold, trunk mobility, and mental health. For each outcome, Standardized mean differences (SMD) or mean differences (MD) and 95% confidence intervals (CIs) were calculated. Results: Eight RCTs (n = 375) were included based on inclusion and exclusion criteria. The meta-analysis showed that the overall efficacy of myofascial release for CLBP was significant, including two aspects: pain [SMD = -0.37, 95% CI (-0.67, -0.08), I 2 = 46%, P = 0.01] and physical function [SMD = -0.43, 95% CI (-0.75, -0.12), I 2 = 44%, P = 0.007]. However, myofascial release did not significantly improve quality of life [SMD = 0.13, 95% CI (-0.38, 0.64), I 2 = 53%, P = 0.62], balance function [SMD = 0.58, 95% CI (-0.49, 1.64), I 2 = 82%, P = 0.29], pain pressure-threshold [SMD = 0.03,95% CI (-0.75, 0.69), I 2 = 73%, P = 0.93], trunk mobility [SMD = 1.02, 95% CI (-0.09, 2.13), I 2 = 92%, P = 0.07] and mental health [SMD = -0.06, 95% CI (-0.83, 0.71), I 2 = 73%, P = 0.88]. Conclusions: In this study, we systematically reviewed and quantified the efficacy of myofascial release in treating CLBP. The meta-analysis results showed that myofascial release significantly improved pain and physical function in patients with CLBP but had no significant effects on balance function, pain pressure-threshold, trunk mobility, mental health, and quality of life. However, due to the low quality and a small number of included literature, more and more rigorously designed RCTs should be included in the future to verify these conclusions.

The Efficacy of Backward Walking on Static Stability, Proprioception, Pain, and Physical Function of Patients with Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: Impaired static stability and proprioception have been observed in individuals with knee osteoarthritis (KOA), which serves as a major factor increasing risk of fall. This study aimed to investigate the effects of backward walking (BW) on static stability, proprioception, pain, and physical function in KOA patients. METHODS: Thirty-two subjects with knee osteoarthritis were randomly assigned to either an BW group (BG, n = 16) or a control group (CG, n = 16). The participants in the BG received combination treatment of a 4-week BW training and conventional treatments, while those in the CG was treated with conventional treatments alone. All the participants were tested for the assessment of static stability [center of pressure (COP) sway, including sway length (SL, mm) and sway area (SA, mm2)] and proprioception [average trajectory error (ATE, %) and completion time (CT, second)]. Additionally, pain and knee function scores were measured by the numerical rating scale (NRS) and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, respectively. The assessments were conducted before and after intervention. RESULTS: The COP sway (SA and SL), ATE, NRS, and WOMAC showed a significant decline at week 4 in the two groups in contrast to their baseline (P < 0.05). Moreover, after 4-week intervention, the SA [(610.50 ± 464.26) mm2 vs. (538.69 ± 420.52) mm2], NRS [(1.56 ± 0.63) vs. (2.25 ± 0.86)], and WOMAC [(11.69 ± 2.50) vs. (16.19 ± 3.94)] showed a significantly greater decrease in the BG compared to the CG (P < 0.05, respectively). However, the proprioception (ATE and CT) was closely similar between both groups at week 4 (P > 0.05). CONCLUSION: BW is an effective adjunct to conventional treatment in reducing pain, improving physical function and static stability for KOA patients. It should be taken into consideration when developing rehabilitation programs for people with KOA.

Effect of Pilates on Glucose and Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: The benefits of Pilates for blood glucose and lipids remain unclear. The purpose of this study was to examine the effect of Pilates on their levels. Methods: Searches were conducted in five databases to identify relevant articles published until October 29, 2020. Paired reviewers independently screened the articles and extracted data from each included study. Meta-analysis was performed to assess the effects of Pilates on blood glucose and lipids. Subgroup analyses and sensitivity analyses were conducted to explore heterogeneity. Results: According to the inclusion and exclusion criteria, 15 randomized controlled trials (RCTs) comprising 587 participants were included in the study. Overall, the Pilates group (PG) had a significantly greater reduction in post-prandial blood glucose than the control group (CG) (MD = -22.25 mg/dL, 95% CI: [-28.34, 16.17] mg/dL, P < 0.00001, I2 = 0%); glycated hemoglobin (HbA1c) (MD = -0.78%, 95% CI: [-1.13, -0.42]%, P < 0.0001, I2 = 88%); total cholesterol (TC) (MD = -20.90 mg/dL, 95% CI: [-37.21, -4.60] mg/dL, P = 0.01, I2 = 84%); triglycerides (TG) (MD = -12.59 mg/dL, 95% CI: [-19.88, -5.29] mg/dL, P = 0.0007, I2 = 86%); and low density lipoprotein cholesterol (LDL-C) (MD = -12.39 mg/dL, 95% CI: [-16.82, -7.95] mg/dL, P < 0.00001, I2 = 45%) compared to CG, whereas no significant difference was detected between the two groups in fasting blood glucose (MD = -7.04 mg/dL, 95% CI: [-17.26, 3.17] mg/dL, P = 0.18, I2 = 93%), insulin (MD = -1.44 µU/mL, 95% CI: [-4.30, 1.41] µU/mL, P = 0.32, I2 = 0%); and high density lipoprotein cholesterol (HDL-C) (MD = -2.68 mg/dL, 95% CI: [-9.03, 3.67] mg/dL, P = 0.41, I2 = 89%). However, by subgroup analysis, we found that compared to the CG, PG showed no significant improvement in blood glucose and lipids levels for non-diabetics, while it presented a significantly greater decrease in post-prandial blood glucose, TC, TG, and LDL-C for diabetic patients. Notably, for diabetic patients, Pilates and medication treatments showed no significant reduction in fasting blood glucose (MD = -7.00 mg/dL, 95% CI: [-26.06, 12.06] mg/dL, P = 0.40) and HbA1c (MD = -0.23%, 95% CI: [-0.58, 0.13]%, P = 0.21, I2 = 0%) than medications treatment used alone, and Pilates combined with medications and dietary treatments presented no significant improvement in fasting blood glucose than a combination of medications and dietary treatments (MD = -10.90 mg/dL, 95% CI: [-32.35, 10.54] mg/dL, P = 0.32, I2 = 94%). Conclusions: Overall, Pilates could improve post-prandial blood glucose, fasting blood glucose, HbA1c, TG, TC, and LDL-C for diabetic patients, which could be influenced by its duration and intensity. Moreover, it had no significant effect on blood glucose and lipids for non-diabetic individuals. However, Pilates, as an adjunctive treatment to medications was not superior to medications used alone in lowering fasting blood glucose and HbA1c. Furthermore, Pilates combined with medications and dietary treatments showed no significant improvement in fasting blood glucose, whereas it had a greater reduction in post-prandial blood glucose and HbA1c for diabetic patients. Systematic Review Registration: https://osf.io/xgv6w.

Pilates for Overweight or Obesity: A Meta-Analysis.

Background: Evidence for the efficacy of Pilates for the modulation of body weight and body composition is unclear. Objective: This meta-analysis aimed to evaluate the effects of Pilates on body weight and body composition in adults with overweight or obesity. Data Sources: The PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and EMBASE databases were systematically searched from the inception dates to 12 November 2020 for relevant randomized controlled trials (RCTs). Study Selection: Randomized controlled trials comparing Pilates with other physical exercises or without any intervention were included. Data Extraction and Synthesis: Three reviewers independently performed the data extraction and assessed study quality. The mean differences (MDs) and 95% confidence intervals (CIs) for pooled data were calculated. Main Outcomes and Measures: Outcome measures were body weight, body mass index (BMI), body fat percentage, lean body mass, and waist circumference. Results: Eleven RCTs with 393 subjects were included. This study revealed that Pilates dramatically reduces body weight (MD = -2.40, 95% CI: [-4.04, -0.77], P = 0.004, I 2 = 51%), BMI (MD = -1.17, 95% CI: [-1.85, -0.50], P = 0.0006, I 2 = 61%), and body fat percentage (MD = -4.22, 95% CI: [-6.44, -2.01], P = 0.0002, I 2 = 88%) in adults with overweight or obesity. The reduction in body weight and body fat percentage appears to be more pronounced in studies including participants with obesity only, and the efficacy of Pilates for the improvement of body weight and BMI appears to be more evident in longer intervention duration. However, Pilates has no significant effect on waist circumference (MD = -2.65, 95% CI: [-6.84, 1.55], P = 0.22, I 2 = 0%) and lean body mass (MD = -0.00, 95% CI: [-1.40, 1.40], P = 1.00, I 2 = 23%). Conclusions: Pilates dramatically reduces body weight, BMI, and body fat percentage in adults with overweight or obesity. Large-scale and well-designed RCTs with improved methodology and reporting are urgently needed to further confirm these results.

Yoga for Treating Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Purpose: Rheumatoid arthritis (RA) is a pervasive inflammatory autoimmune disease that seriously impairs human health and requires more effective non-pharmacologic treatment approaches. This study aims to systematically review and evaluate the efficacy of yoga for patients with RA. Methods: Medline (through PubMed), Cochrane Library, EMBASE (through SCOPUS), and Web of Science database were screened through for articles published until 20 July 2020. Randomized controlled trials (RCTs) of yoga in patients with RA were included. Outcomes measures were pain, physical function, disease activity, inflammatory cytokines, and grip strength. For each outcome, standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Result: Ten trials including 840 patients with RA aged 30-70 years were identified, with 86% female participants. Meta-analysis revealed a statistically significant overall effect in favor of yoga for physical function (HAQ-DI) (5 RCTs; SMD = -0.32, 95% CI -0.58 to -0.05, I 2 = 15%, P = 0.02), disease activity (DAS-28) (4 RCTs; SMD = -0.38, 95% CI -0.71 to -0.06, I 2 = 41%, P = 0.02) and grip strength (2 RCTs; SMD = 1.30, 95% CI 0.47-2.13, I 2 = 63%, P = 0.002). No effects were found for pain, tender joints, swollen joints count or inflammatory cytokines (i.e., CRP, ESR, IL-6, and TNF-α). Summary: The findings of this meta-analysis indicate that yoga may be beneficial for improving physical function, disease activity, and grip strength in patients with RA. However, the balance of evidence showed that yoga had no significant effect in improving pain, tender joints, swollen joints count, and inflammatory cytokines in patients suffering from RA. Considering methodological limitations, small sample size, and low-quality, we draw a very cautious conclusion in the results of the estimate of the effect. High-quality and large-scale RCTs are urgently needed in the future, and the real result may be substantially different.

Comprehensive Analysis of Novel lncRNA-TF Regulatory Cross Talks and Identification of Core lncRNA-TF Feedback Loops in Sarcoma.

Sarcomas are a broad family of cancers that arise from cells of mesenchymal origin in virtually every tissue of the body. Some transcription factors (TFs) have been reported to be involved in the pathogenesis and metastasis of sarcomas. The expression of certain long noncoding RNAs (lncRNAs) has been correlated with the degree of cancer prognosis. There is an urgent need to effectively integrate TFs and lncRNA/microRNA/mRNA regulatory axis and further identify more key regulators that play crucial roles in sarcomas. We performed a network-based computational analysis to investigate the lncRNA-TF cross talks via integrating lncRNA-TF ceRNA interactions and TF-TF protein-protein interactions. Multiple topology analyses were performed to the sarcomas-related global lncRNA-TF network. Several lncRNAs or TFs with central topology structures were identified as key regulators and used to locate a hub-associated lncRNA-TF subnetwork. Three functional modules were identified from the sarcomas-related global lncRNA-TF network, which have shown significant pathway enrichment and prognosis capability. The lncRNAs and TFs of these modules were shown to participate in sarcoma-related biological phenomena through involving in mitogen-activated protein kinases (MAPK), Jak-STAT, and transforming growth factor (TGF-beta) signaling pathways. More importantly, a subset of core lncRNA-TF cross talks that might form positive feedback loops to control biological processes of sarcomas was identified. These core lncRNA-TF positive feedback loops showed more TF binding affinity than other lncRNAs. All the results can help us uncover the molecular mechanism of sarcomas and provide a novel way for diagnosis biomarker and therapeutic target identification.