Total flavonoids of Rhizoma Drynariae enhances CD31hiEmcnhi vessel formation and subsequent bone regeneration in rat models of distraction osteogenesis by activating PDGF­BB/VEGF/RUNX2/OSX signaling axis.

Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney­tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co­immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow­derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet­derived growth factor (PDGF)­BB, VEGF, runt­related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription­quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF­BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF­BB. The protein and mRNA levels of PDGF­BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF­BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic­osteogenic coupling to regenerate bone defects during DO via the PDGF­BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.

Electroacupuncture as an Adjuvant Approach to Rehabilitation during Postacute Phase after Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Increasing attention has been paid to electroacupuncture (EA) for promoting postoperative rehabilitation, but the effectiveness of EA for rehabilitation after total knee arthroplasty (TKA) remains obscure. OBJECTIVE: To examine the effect of EA on rehabilitation after TKA. METHODS: Database searches on PubMed, CINAHL, Embase, and China National Knowledge Infrastructure (CNKI) were carried out to obtain articles, from inception to 15 October 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was conducted to assess the effects of acupuncture on pain, range of knee motion, and postoperative vomiting after TKA. RESULTS: In the current study, a total of ten randomized clinical trials were included according to the inclusion and exclusion criteria. Compared to basic treatment, EA combined with basic treatment showed a significantly greater pain reduction on 3, 7, and 14 days postoperatively after TKA. However, we found that EA had no significant improvement in enhancing the range of knee motion and decreasing the percentage of vomiting. Subgroup analysis suggested that a combination of EA and rehabilitation training was superior to rehabilitation training in pain relief, while EA combined with celecoxib capsules showed no significant difference in improving pain compared to celecoxib capsules alone. CONCLUSIONS: In the postacute phase after TKA, EA, as a supplementary treatment, could reduce postoperative pain, but no evidence supported the benefits of EA for improving ROM of knee and decreasing the ratio of vomiting. Additional high-quality and large-scale RCTs are warranted.

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 electroacupuncture on postoperative cognitive dysfunction for patients undergoing total knee arthroplasty: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Electroacupuncture is increasingly used in rehabilitation for postoperative cognitive dysfunction (POCD), but relevant evidence remains unclear for patients receiving total knee arthroplasty (TKA). METHODS: The databases research of PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI) will be conducted from inception to December 31, 2020. The relevant randomized controlled trials (RCTs) from data will be screened one by one. The remaining studies that meet the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Paired 2 reviewers will assess quality of the included studies and publication bias by using the Cochrane Collaboration risk of bias tool, and Egger test and Begg test respectively. And grading of recommendations assessment, development and evaluation (GRADE) will be used to estimate the quality of evidence. RESULTS: In this study, we will analyze the effect of electroacupuncture on Mini-Mental State Examination (MMSE), interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S100-ß protein, and adverse events for patients with TKA. CONCLUSION: Our findings will provide evidence for the effectiveness of electroacupuncture on the treatment and prevention of POCD for TKA patients. REGISTRATION NUMBER: Available at: https://osf.io/azyt9 (DOI number: 10.17605/OSF.IO/AZYT9).

Evidence of Chinese herbal fumigation for knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (KOA) is the most common cause of musculoskeletal pain and disability worldwide. Chinese herbal fumigation, an external therapy, is commonly used for the treatment of KOA, while there is no systematic review or meta-analysis designed to evaluate the effects of Chinese herbal fumigation on KOA. METHODS: Seven databases including Cochrane Central Register of Controlled Trials, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang data, VIP, and Chinese Biomedical Literature Database will be searched up to October 31, 2020. Data that meet the inclusion criteria will be extracted and analyzed by using RevMan V.5.3 software. Two reviewers will assess quality of the included studies based on the Cochrane Collaboration risk of bias tool. The funnel plot and Begg test will be used to evaluate publication bias. And Grading of Recommendations Assessment, Development and Evaluation will be employed to assess the quality of evidence. RESULTS: This study will provide high-quality evidence for Chinese herbal fumigation for the treatment of KOA in terms of effectiveness and safety. CONCLUSION: This systematic review will provide evidence to help us confirm the clinical efficacy of Chinese herbal fumigation in the treatment of KOA.

Electroacupuncture for the Prevention of Postoperative Cognitive Dysfunction Among Older Adults Undergoing Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Postoperative cognitive dysfunction (POCD) is a common surgical complication in elderly patients undergoing hip and knee replacement. Electroacupuncture (EA) may have a protective effect on postoperative cognitive function, but relevant evidence remains uncertain. Objective: To systematically evaluate the evidence of EA for the prevention of POCD after total joint arthroplasty. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and Chinese Biomedical Literature Database (CBM) databases were searched until May 1, 2021. Randomized controlled trials (RCTs) in which patients undergoing hip and knee replacement pretreated with EA for preventing POCD were included. The risk of bias was assessed by the Cochrane Collaboration tool. Meta-analysis was performed using Review Manager version 5.4. Results: A total of 11 RCTs with 949 patients were identified. Meta-analysis showed that compared with controls, EA pretreatment significantly reduced the incidence of POCD at 1, 3, and 7 days and 3 and 6 months after the operation. EA was also superior in improving the Mini-Mental State Examination (MMSE) scores on the third postoperative day, but not on the first postoperative day. Neuron-specific enolase (NSE) and interleukin-1ß (IL-1ß) in the EA group were significantly lower than that in the control group. There was no difference in S100ß between the EA group and the control group. Compared to the control group, tumor necrosis factor-α (TNF-α) levels were not significantly lower in the EA group at postoperative hour 0, while significantly decreased at postoperative hours 24 and 48. Conclusion: Our results suggest that EA pretreatment is an effective adjunctive therapy for reducing the incidence of POCD for patients receiving total joint replacement surgery. Its effect was embodied in improving the MMSE scores and NSE, IL-1ß, and TNF-α levels, whereas it had no significant effect on S100ß levels. Meanwhile, the benefits of EA for improving POCD need further strengthening and support from more large-scale, high-quality, and good-homogeneity RCTs. Systematic Review Registration: https://osf.io/xb3e8.

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.

Total Flavonoids of Rhizoma Drynariae Enhances Angiogenic-Osteogenic Coupling During Distraction Osteogenesis by Promoting Type H Vessel Formation Through PDGF-BB/PDGFR-ß Instead of HIF-1α/ VEGF Axis.

Background: Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying traditional Chinese medicine Rhizoma Rrynariae, has been proved to be effective in treating osteoporosis, bone fractures and defects. However, pharmacological effects of TFRD on type H vessels, angiogenic-osteogenic coupling in distraction osteogenesis (DO) and the mechanism remain unclear. This study aims at investigating whether type H vessels exist in the DO model, effects of TFRD on angiogenic-osteogenic coupling and further elucidating the underlying mechanism. Methods: Rats models of DO and bone fracture (FR) were established, and then were separately divided into TFRD and control subgroups. Imageological and histological analyses were performed to assess bone and vessel formation. Immunofluorescent staining of CD31 and endomucin (Emcn) was conducted to determine type H vessel formation. Matrigel tube formation, ALP and Alizarin Red S staining assays were performed to test the effects of TFRD on angiogenesis or osteogenesis of endothelial precursor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of HIF-1α, VEGF, PDGF-BB, RUNX2 and OSX were determined by ELISA, qPCR or western blot, respectively. Results: The in vivo results indicated more formed type H vessels in DO groups than in FR groups and TFRD obviously increased the abundance of type H vessels. Moreover, groups with higher abundance of type H vessels showed better angiogenesis and osteogenesis outcomes. Further in vitro experiments showed that TFRD significantly promoted while blocking PDGF-BB remarkably suppressed the angiogenic activity of EPCs under stress conditions. The levels of p-AKT and p-ERK1/2, downstream mediators of the PDGF-BB pathway, were up-regulated by TFRD but blocked by function blocking anti-PDGF-BB antibody. In contrast, the activated AKT and ERK1/2 and corresponding tube formation were not affected by the HIF-1α inhibitor. Besides, blocking PDGF-BB inhibited the osteogenic differentiation of the stretched BMSCs, but TFRD enhanced the osteogenic activity of BMSCs and ameliorated the inhibition, with more calcium nodes, higher ALP activity and mRNA and protein levels of RUNX2 and OSX. Conclusion: Type H vessels exist in the DO model and TFRD enhances angiogenic-osteogenic coupling during DO by promoting type H vessel formation via PDGF-BB/PDGFR-ß instead of HIF-1α/VEGF axis.

Effects of Bushen Huoxue method for female with decreased ovarian reserve: A protocol for systematic review and meta-analysis.

BACKGROUND: Decreased ovarian reserve (DOR) is a common reproductive barrier in female. Bushen Huoxue (BSHX) method of TCM is widely applied to treat DOR clinically. The purpose of this study is to provide a systemic and comprehensive evaluation of BSHX in the treatment of DOR. METHODS: We have registered this protocol with OSF registry and the DOI is 10.17605/OSF.IO/QNUE2. We will search 4 English databases (PubMed, EMBASE, MEDLINE, Cochrane Library) and four Chinese databases (China national knowledge infrastructure database, Wanfang database, VIP and Superstar database) from their inception to August 10, 2020. Two authors will search and extract independently all related studies. RevMan 5.3 software will be applied to synthesize data. RESULTS: The results of this study will be published in a scientific journal after peer-review. CONCLUSION: This systematic review will provide reliable evidences for clinicians, and help them make decisions in DOR management.

Comparison between Tonifying Kidney Yang and Yin in Treating Segmental Bone Defects Based on the Induced Membrane Technique: An Experimental Study in a Rat Model.

Tonifying kidney therapy consisting of tonifying kidney yang and yin is the basic principle of Chinese medicine in treating segmental bone defects (SBDs). Previous studies have demonstrated the presence of the differences between tonifying kidney yang and yin in bone metabolism of osteoporosis and distraction osteogenesis models. However, whether the difference between the two tonifying kidney methods in bone repair for the induced membrane (IM) technique occurs or what is the difference remain unclear. Angiogeneic-osteogenic coupling plays an important role in bone repair and the induced membrane couples angiogenesis with the later osteogenesis during the IM process. This study aimed at investigating the effects of tonifying kidney yang (total flavonoids of Rhizoma Drynariae, TFRD) and yin (plastrum testudinis extract, PTE) on angiogenesis and osteogenesis in the IM-treated SBDs. Rats of 6 mm tibia bone defect model treated with IM were divided into five groups: the control group, the model group, the tonifying kidney yang group (TFRD-treated group), the tonifying kidney yin group (PTE-treated group), and the western medicine group. At 4 weeks after insertion of the polymethylmethacrylate (PMMA), three caudal vertebrae from the tail in each rat were implanted into the 6 mm defect gap. Radiographical, histological, immunohistochemical, and immunofluorescent analyses were performed to assess bone and vessel formation at 4 or 12 weeks after insertion of the PMMA, respectively. Our results revealed that TFRD and PTE were beneficial to both angiogenesis and osteogenesis. TFRD exerted a better effect on angiogenesis than PTE and achieved a better result in stage 1 rather than in stage 2 of IM, whereas PTE was superior to TFRD in osteogenesis and achieved a better result in stage 2 instead of stage 1. Collectively, these findings elucidated the beneficial effects of tonifying kidney yang and yin on angiogenesis and osteogenesis of SBD repair during the IM process, as well as the difference that tonifying kidney yang surpasses tonifying kidney yin in angiogenesis while tonifying kidney yin outperforms tonifying kidney yang in osteogenesis, which suggests that the combination between the application of tonifying kidney yang method in stage 1 of IM and tonifying kidney yin method in stage 2 may achieve better repair efficiency.

Acupuncture for Rehabilitation After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: There is an increasing interest in acupuncture for promoting post-operative rehabilitation, but the effectiveness of acupuncture for rehabilitation after total knee arthroplasty (TKA) remains controversial. Objective: This study aims to investigate the effect of acupuncture on rehabilitation after TKA. Methods: Database searches of PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI) were conducted to obtain articles published until August 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was performed to examine the effects of acupuncture on pain, range of knee motion, function, and nausea/vomiting after TKA. Results: A total of nine randomized clinical trials were included according to the inclusion and exclusion criteria in this review. Compared with routine treatment, acupuncture combined with routine treatment showed a significantly greater pain reduction at 8, 12, 24, and 48 h post-operatively after TKA. Meanwhile, we found that the acupuncture groups showed a significant function improvement and a lower percentage of nausea/vomiting in comparison with the control groups after operation. However, acupuncture groups demonstrated no statistically significant improvement in post-operative pain at 4 h, 7 days, 14 days, and more than 21 days, and no significant difference in range of knee motion was observed between the acupuncture groups and control groups after surgery. Conclusions: Acupuncture, as a supplementary treatment after TKA, could improve function and reduce nausea/vomiting. However, the effect of acupuncture on pain relief may be mainly achieved within post-operative 48 h, and it had no efficacy in improving range of knee motion. More large-scale and high-quality studies are warranted.

Pas de deux: An Intricate Dance of Anther Smut and Its Host.

The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host Silene latifolia serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores. In the current study, transcriptome analyses of the fungus and its host were conducted during discrete stages of bud development so as to identify changes in fungal gene expression that lead to spore development and to identify changes associated with infection in the host plant. In contrast to early biotrophic phase stages of infection for the fungus, the latter stages involve tissue necrosis and in the case of infected female flowers, further changes in the developmental program in which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via Illumina RNA sequencing revealed enrichment of fungal genes encoding small secreted proteins, with hallmarks of effectors and genes found to be relatively unique to the Microbotryum species complex. Host gene expression analyses also identified interesting sets of genes up-regulated, including those involving stress response, host defense response, and several agamous-like MADS-box genes (AGL61 and AGL80), predicted to interact and be involved in male gametophyte development.