Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy.

BACKGROUND: Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs. METHODS: Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au-S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated. RESULT: The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed. CONCLUSION: The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.

Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin.

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.

Hybrid nanopotentiators with dual cascade amplification for glioma combined interventional therapy.

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2+ BC) due to the challenges in addressing blood circulation and tumor accumulation. Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2+ BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a "nano-thermal-bomb". Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor. Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2+ BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2+ cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions. Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy. In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

B1-B2 transition in shock-compressed MgO.

Magnesium oxide (MgO) is a major component of the Earth's mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl B1 crystal structure to a CsCl B2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature. We identify the B1 to B2 phase transition between 397 and 425 gigapascal (around 9700 kelvin), in agreement with recent theory that accounts for phonon anharmonicity. From 425 to 493 gigapascal, we observe a mixed-phase region of B1 and B2 coexistence. The transformation follows the Watanabe-Tokonami-Morimoto mechanism. Our data are consistent with B2-liquid coexistence above 500 gigapascal and complete melting at 634 gigapascal. This study bridges the gap between previous theoretical and experimental studies, providing insights into the timescale of this phase transition.

Reliability of foot posture index (FPI-6) for evaluating foot posture in patients with knee osteoarthritis.

Objective: To determine the reliability of FPI-6 in the assessment of foot posture in patients with knee osteoarthritis (KOA). Methods: Thirty volunteers with KOA (23 females, 7 males) were included in this study, assessed by two raters and at three different moments. Inter-rater and test-retest reliability were assessed with Cohen's Weighted Kappa (Kw) and Intraclass Correlation Coefficient (ICC). Bland-Altman plots and respective 95% limits of agreement (LOA) were used to assess both inter-rater and test-retest agreement and identify systematic bias. Moreover, the internal consistency of FPI-6 was assessed by Spearman's correlation coefficient. Results: FPI-6 total score showed a substantial inter-rater (Kw = .66) and test-retest reliability (Kw = .72). The six items of FPI-6 demonstrated inter-rater and test-retest reliability varying from fair to substantial (Kw = .33 to .76 and Kw = .40 to .78, respectively). Bland-Altman plots and respective 95% LOA indicated that there appeared no systematic bias and the acceptable agreement of FPI-6 total score for inter-rater and test-retest was excellent. There was a statistically significant positive correlation between each item and the total score of FPI-6, which indicated that FPI-6 had good internal consistency. Conclusion: In conclusion, the reliability of FPI-6 total score and the six items of FPI-6 were fair to substantial. The results can provide a reliable way for clinicians and researchers to implement the assessment of foot posture in patients with KOA.

Comparison of the asymmetries in muscle mass, biomechanical property and muscle activation asymmetry of quadriceps femoris between patients with unilateral and bilateral knee osteoarthritis.

Background: More and more attention has been paid to the research of muscle mass and muscle quality of quadriceps femoris (QF) in knee osteoarthritis (KOA). This study aimed to explore the asymmetric changes of muscle mass, biomechanical property and muscle activation in the inter-limbs QF of KOA patients, and tried to provide a novel insight for the evaluation, prevention and treatment of KOA. Methods: A total of 56 Participants with unilateral or bilateral KOA were included in this study: 30 patients with unilateral pain and 26 patients with bilateral pain were assigned to the bilateral group (BG) and unilateral group (UG), respectively. The symptom severity of bilateral lower limbs was evaluated by visual analogue scale, and the relatively serious leg (RSL) and relatively moderate leg (RML) were classified. The thickness of rectus femoris (RF), vastus intermedius (VI), vastus medialis (VM) and vastus lateralis (VL) were measured by ultrasound. The Shear wave elastography (SWE) techniqie was used to measure the shear modulus of RF, VM and VL. Surface electromyography (sEMG) was used to assess the root mean square (RMS) of the RF, VM, and VL during straight leg raising in a sitting position and squatting task. We calculated the asymmetry indexes of inter-limbs for the corresponding indices of the measured muscles. Result: Thickness of RF, VI and VL of RSL was lower than those on RML (p < 0.05), and thickness of VM was lower more significant (p < 0.01). Thickness of RF, VI and VL of RSL was also lower than those of RML in BG (p < 0.05), however, there was no significant difference in VM thickness (p > 0.05). There were no significant difference in Asymmetry indexes of all measured muscle thickness between the two groups (p > 0.05). The Shear modulus of RF, VM, and VL in the RML of UG and BG was higher than those in the RSL (p < 0.05). In sitting and straight leg raising task, the RMS of RF, VM and VL in RML were higher than those in RSL, UG and BG both showed this trend (p < 0.05). About squatting task, in UG, the RMS of the three muscles in RML of patients were also higher than those in the RSL (p < 0.05). However, the difference was not significant in BG (p > 0.05). In the straight leg raising task, the asymmetry indexes of RMS in RF, VM, and VL of both the two groups were positively correlated with VAS scores (p < 0.05). Conclusion: The muscle thickness, shear modulus and muscle activation electromyography of QF in RML were higher than those of RSL in unilateral KOA patients. The VM of RML in bilateral KOA patients may show muscle thickness degeneration earlier, which is closer to the VM of RSL. The shear modulus of RF, VM, and VL were higher on the RML side during the single-leg task, but there may be passive compensation for muscle activation in both lower limbs during the bipedal task. In conclusion, there is a general asymmetry of QF muscle mass, biomechanics Characteristic and performance in patients with KOA, which may provide new ideas for the assessment, treatment and rehabilitation of the disease.

New Developments and Opportunities of Microbiota in Treating Breast Cancers.

Despite the prevalence of breast cancer (BC), over half of BC cases are unrelated to known risk factors, which highlights the importance of uncovering more cancer-related factors. Currently, the microbiota has been proven to be a potent modulator of the tumor environment in BC, which regulates the immune balance in tumor-related networks. Through a large amount of data accumulation, the microbiota has shown many possibilities to reveal more insights into the development or control of BC. To expand the potential benefits of patients with BC, this study discusses the distribution profile and the effect mechanism of BC-related microbiota on tumors and further discusses its impact on different tumor therapies. Finally, we summarize the possibility of targeting microbiological therapies to improve BC treatment or in combination with other therapies.

Effects of Gut Microbiota on Host Adaptive Immunity Under Immune Homeostasis and Tumor Pathology State.

Gut microbiota stimulate and shape the body's adaptive immune response through bacterial components and its active metabolites, which orchestrates the formation and maintenance of the body's immune homeostasis. In addition, the imbalances in microbiota-adaptive immunity contribute to the development of tumor and the antitumor efficiency of a series of antitumor therapies at the preclinical and clinical levels. Regardless of significant results, the regulation of gut microbiota on adaptive immunity in immune homeostasis and tumors needs a more thorough understanding. Herein, we highlighted the comprehensive knowledge, status, and limitations in the mechanism of microbiome interaction with adaptive immunity and put forward the prospect of how to translate these insights in inhibiting tumor progression and enhancing the efficacy of antitumor interventions.

Effects of language background on executive function: Transfer across task and modality.

The relation between linguistic experience and cognitive function has been of great interest, but recent investigations of this question have produced widely disparate results, ranging from proposals for a "bilingual advantage," to a "bilingual disadvantage," to claims of no difference at all as a function of language. There are many possible sources for this lack of consensus, including the heterogeneity of bilingual populations, and the choice of different tasks and implementations across labs. We propose that another reason for this inconsistency is the task demands of transferring from linguistic experience to laboratory tasks can differ greatly as the task is modified. In this study, we show that task modality (visual, audio, and orthographic) can yield different patterns of performance between monolingual and multilingual participants. The very same task can show similarities or differences in performance, as a function of modality. In turn, this may be explained by the distance of transfer - how close (or far) the laboratory task is to the day to day lived experience of language usage. We suggest that embodiment may provide a useful framework for thinking about task transfer by helping to define the processes of linguistic production and comprehension in ways that are easily connected to task manipulations.

Production and immunogenicity of a deoxyribonucleic acid Alphavirus vaccine expressing classical swine fever virus E2-Erns protein and porcine Circovirus Cap-Rep protein.

Classical swine fever virus (CSFV) and porcine Circovirus type 2 (PCV2) are economically pivotal infectious disease viruses of swine. Alphaviral RNA replicon plasmids have been used as an important vector for constructing nucleic acid vaccines. Here, we aimed to construct a recombinant alphaviral plasmid vaccine pSCA1-E2-Erns-Cap-Rep for the prevention and control of CSFV and PCV2. Our results showed that the recombinant alphaviral plasmid vaccine pSCA1-E2-Erns-Cap-Rep was successfully constructed. The vaccine encoding E2 and Erns of CSFV, Cap, and Rep of PCV2 can induce E2, Erns, Cap, and Rep protein expression. ELISA analysis showed that mice-immunized pSCA1-E2-Erns-Cap-Rep plasmid vaccine produced higher anti-CSFV- and anti-PCV2-specific antibodies with dose- and time-dependent manners. Furthermore, neutralizing assays were measured using IF and ELISA methods. The results showed the production of neutralizing antibodies could neutralize CSFV (up to 210.13) and PCV2 (28.6) effectively, which exhibited the immune efficacy of the pSCA1-E2-Erns-Cap-Rep plasmid vaccine. Taken together, this pSCA1-E2-Erns-Cp-Rep plasmid vaccine could be considered a novel candidate vaccine against CSFV and PCV2.

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

Background: Knee osteoarthritis (KOA) is a high incidence chronic joint disease that seriously affects patients' quality of life, and current treatment methods have limited efficacy. Self-management may be an effective strategy for KOA, and clinicians have been showing increased interest recently. However, the effectiveness of self-management for KOA remains controversial. Purpose: This study aims to systematically evaluate the effectiveness of self-management for KOA. Methods: We screened articles published in MEDLINE, Cochrane Library, EMBASE, and Web of Science until September 17, 2021. The main outcomes included pain, knee function, stiffness, WOMAC (total), physical function, arthritis self-efficacy (ASE-pain), arthritis self-efficacy (ASE-other symptoms), mental health, and quality of life. Results: Thirteen randomized controlled trials (RCTs) were finally included (n = 1610). Meta-analysis showed differences in pain, knee function, stiffness, ASE-pain, ASE-other symptoms, mental health, and quality of life between the self-management and control groups. Of the nine outcomes evaluated, four were highly heterogeneous, and the quality of evidence ranged from very low to moderate. Conclusion: The meta-analysis results showed that self-management might help improve the pain, knee function, stiffness, ASE, mental health, and quality of life in patients with KOA. However, it has no significant effect on WOMAC (total) and physical function. Considering that this study has some limitations, we cannot draw clear conclusions based on the results of this study. Nevertheless, we offer much needed insight and encourage more rigorously designed and implemented RCTs in the future to substantiate our conclusions.

A triple enhanced permeable gold nanoraspberry designed for positive feedback interventional therapy.

Due to the unique microenvironment, nanoparticles cannot easily penetrate deeply into tumours, which decreases their therapeutic efficacy. Thus, new strategies should be developed to solve this problem and increase the efficacy of nanomedicine. In this study, gold nanoraspberries (GNRs) were constructed using ultrasmall gold nanospheres (UGNPs) with a matrix metalloproteinase (MMP)-2/9-sensitive peptide as a cross-linking agent. These UGNPs were then modified with trastuzumab (TRA) and mertansine derivatives (DM1) via the AuS bond. TRA targets the human epidermal growth factor receptor-2 (Her-2) which is overexpressed on Her-2+ breast cancer cells. The AuS bond in GNRs-DM1 can be replaced by the free sulfhydryl group of GSH, which could achieve GSH dependent redox responsive release of the drug. In the mouse model of Her-2+ breast cancer, a "positive feedback" triple enhanced penetration platform was construct to treat tumours. Firstly, near-infrared light-triggered photothermal conversion increased vascular permeability, resulting in nanoparticle penetration. Secondly, GNRs disintegrated into UGNPs in response to stimulation with MMPs. GNRs with larger particle sizes reached the tumour site through EPR effect and active targeting. Meanwhile, UGNPs with smaller particle sizes penetrated deeply into the tumour through diffusion. Thirdly, the UGNPs transformed activated cancer-associated fibroblasts to a quiescent state, which reduced intercellular pressure and promoted the penetration of the UGNPs into the interior of the tumour. In turn, an increase in the number of nanoparticles penetrating into the tumour led to a "positive feedback" loop of triple enhanced photothermal effects and further self-amplify the permeability in vivo. Interventional photothermal therapy (IPTT) was used to improve the therapeutic efficacy by reducing the laser power attenuation caused by percutaneous irradiation. The GNRs also showed excellent multimode imaging (computed tomography, photoacoustic imaging and photothermal imaging) capabilities and high anti-tumour efficacy due to efficient tumour targeting and triple enhanced deep penetration into the tumour site. Thus, these MMP-2/redox dual-responsive GNRs are promising carriers of drugs targeting human epidermal growth factor receptor 2+ breast cancer.

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.

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.

Preoperative Strength Training for Clinical Outcomes Before and After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

Background: There is an increasing interest in preoperative strength training for promoting post-operative rehabilitation, but the effectiveness of preoperative strength training for clinical outcomes after total knee arthroplasty (TKA) remains controversial. Objective: This study aims to systematically evaluate the effect of preoperative strength training on clinical outcomes before and after TKA. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE databases from the inception to November 17, 2021. The meta-analysis was performed to evaluate the effects of preoperative strength training on clinical outcomes before and after TKA. Results: Seven randomized controlled trials (RCTs) were included (n = 306). Immediately before TKA, the pooled results showed significant improvements in pain, knee function, functional ability, stiffness, and physical function in the strength training group compared with the control group, but not in strength (quadriceps), ROM, and WOMAC (total). Compared with the control group, the results indicated strength training had a statistically significant improvement in post-operative knee function, ROM, and functional ability at less than 1 month and 3 months, and had a statistically significant improvement in post-operative strength (quadriceps), stiffness, and WOMAC (total) at 3 months, and had a statistically significant improvement in post-operative pain at 6 months. However, the results indicated strength training had no statistically significant improvement in post-operative strength (quadriceps) at less than 1 month, 6, and 12 months, had no statistically significant improvement in post-operative pain at less than 1 month, 3, and 12 months, had no statistically significant improvement in post-operative knee function at 6 and 12 months, and had no statistically significant improvement in post-operative physical function at 3 months. Conclusions: Preoperative strength training may be beneficial to early rehabilitation after TKA, but the long-term efficacy needs to be further determined. At the same time, more caution should be exercised when interpreting the clinical efficacy of preoperative strength training for TKA.

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.

EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy.

BACKGROUND: Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab-valine-citrulline (vc)-doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells. METHODS: Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody-drug conjugates (ADCs). Then, the ADCs were adsorbed to the surface of the BSA nanoparticles (NPs), which were prepared by a desolvation method to obtain cetuximab-vc-DOX-BSA-NPs. The cetuximab-vc-DOX conjugates adsorbed on the surface of the BSA nanoparticles were determined and optimized by size exclusion chromatography. An in vitro cytotoxicity study was conducted using a colon carcinoma cell line with different EGFR-expression levels to test the selectivity of cetuximab-vc-DOX-NPs. RESULTS: The vc-DOX and cetuximab-vc-DOX conjugates were both synthesized successfully and their structural characteristics confirmed by 1H-NMR and SDS-PAGE. The MTT assay showed stronger cytotoxicity of cetuximab-vc-DOX-NPs versus control IgG-vc-DOX-NPs in EGFR-overexpressing RKO cells. Cellular binding and intracellular accumulation determined by flow cytometry and confocal laser scanning microscopy revealed the strong binding ability of cetuximab-vc-DOX-NPs to RKO cells. The in vivo imaging study demonstrated that cetuximab-vc-DOX-NPs exhibited higher fluorescent intensity in tumor tissues than non-decorated nanoparticles (IgG-vc-DOX-NPs). In vivo tumor inhibition and survival tests showed that cetuximab-vc-DOX-NPs revealed higher tumor inhibition efficacy and lower systemic toxicity than control IgG-vc-DOX- NPs. CONCLUSION: The obtained results emphasize that cetuximab-vc-DOX-NPs, with good tumor-targeting ability and low systemic toxicity, are a promising targeting system for drug delivery.