Pulsed Electromagnetic Fields Combined With Adipose-Derived Stem Cells Protect Ischemic Myocardium by Regulating miR-20a-5p/E2F1/p73 Signaling.

Myocardial infarction (MI) is a serious threat to human health. Although monotherapy with pulsed electromagnetic fields (PEMFs) or adipose-derived stem cells (ADSCs) has been reported to have positive effect on the treatment of MI, a satisfactory outcome has not yet been achieved. In recent years, combination therapy has attracted widespread interest. Herein, we explored the synergistic therapeutic effect of combination therapy with PEMFs and ADSCs on MI and found that the combination of PEMFs and ADSCs effectively reduced infarct size, inhibited cardiomyocyte apoptosis and protected the cardiac function in mice with MI. In addition, bioinformatics analysis and RT-qPCR showed that the combination therapy could affect apoptosis by regulating the expression of miR-20a-5p. A dual-luciferase reporter gene assay also confirmed that the miR-20a-5p could target E2F transcription factor 1 (E2F1) and inhibit cardiomyocyte apoptosis by regulating the E2F1/p73 signaling pathway. Therefore, our study systematically demonstrated the effectiveness of combination therapy on the inhibition of cardiomyocyte apoptosis by regulating the miR-20a-5p/E2F1/p73 signaling pathway in mice with MI. Thus, our study underscored the effectiveness of the combination of PEMFs and ADSCs and identified miR-20a-5p as a promising therapeutic target for the treatment of MI in the future.

Virtual Reality-Based Training in Chronic Low Back Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low back pain is one of the most prevalent pain conditions worldwide. Virtual reality-based training has been used for low back pain as a new treatment strategy. Present evidence indicated that the effectiveness of virtual reality-based training for people with chronic low back pain is inconclusive. OBJECTIVE: This study conducted a meta-analysis to evaluate the immediate- and short-term effects of virtual reality-based training on pain, pain-related fear, and disability in people with chronic low back pain. METHODS: We searched the PubMed, Embase, Web of Science, PEDro, CENTRAL, and CINAHL databases from inception until January 2024. Only randomized controlled trials assessing the effects of virtual reality-based training on individuals with chronic low back pain were selected. The outcomes were focused on pain, pain-related fear measured by the Tampa Scale of Kinesiophobia, and disability measured by the Oswestry Disability Index. The immediate term was defined as the immediate period after intervention, and the short term was defined as 3 to 6 months after intervention. The Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were used to evaluate the quality of the methodology and evidence, respectively. RESULTS: In total, 20 randomized controlled trials involving 1059 patients were eligible for analysis. Virtual reality-based training showed significant improvements in pain (mean difference [MD] -1.43; 95% CI -1.86 to -1.00; I2=95%; P<.001), pain-related fear using the Tampa Scale of Kinesiophobia (MD -5.46; 95% CI -9.40 to 1.52; I2=90%; P=.007), and disability using the Oswestry Disability Index (MD -11.50; 95% CI -20.00 to -3.01; I2=95%; P=.008) in individuals with chronic low back pain immediately after interventions. However, there were no significant differences observed in pain (P=.16), pain-related fear (P=.10), and disability (P=.43) in the short term. CONCLUSIONS: These findings indicated that virtual reality-based training can be used effectively for individuals with chronic low back pain in the immediate term, especially to reduce pain, alleviate pain-related fear, and improve disability. However, the short-term benefits need more high-quality trials to be demonstrated. TRIAL REGISTRATION: PROSPERO CRD42021292633; http://tinyurl.com/25mydxpz.

Monocyte to high-density lipoprotein ratio is associated with mortality in patients with coronary artery diseases.

BACKGROUND: Whether the monocyte to high-density lipoprotein ratio (MHR) is associated with the prognosis of coronary artery disease (CAD) is inconclusive. METHODS: Patients with CAD were enrolled and their data were collected. Blood was sampled within 24 h after admission. Multivariate Cox regression analysis was performed to determine the relationship between the MHR and all-cause mortality as well as complications during hospitalization. RESULTS: We included 5371 patients in our cohort study. Among them, 114 (2.12%) patients died in hospital. MHR was independently associated with all-cause mortality (hazard ratio [HR], 1.81; 95% confidence interval [CI] 1.35, 2.42), cardiovascular mortality (1.69; 1.17, 2.45) and non-cardiovascular mortality (2.04; 1.27, 3.28). This association was only observed in patients with hypertension (P for interaction = 0.003). Patients with higher MHR levels also have a higher risk of complications, including infection, pneumonia, electrolyte disturbance, gastrointestinal bleeding, multiple organ dysfunction syndrome, and disturbance of consciousness. The receiver operating characteristic (ROC) analysis showed that the MHR had higher prognostic values than monocytes and high-density lipoprotein. CONCLUSION: MHR was an independent predictor of all-cause mortality and in-hospital complications in patients with CAD, especially in patients with hypertension.

Effects of home-based cardiac telerehabilitation programs in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Recent advances in telecommunications technology have raised the possibility of telehealth intervention delivering cardiac telerehabilitation, which may provide the efficacy of health services in patients after percutaneous coronary intervention (PCI). This study aimed to investigate the effects of home-based cardiac telerehabilitation (HBCTR) in patients undergoing PCI. METHODS: We performed a comprehensive search of the following electronic databases: PubMed, Cochrane Central, Web of Science, Embase, CNKI, and WANFANG. For the prespecified outcomes, the primary outcomes were results of physical function (the six-minute walking test, 6MWT) and quality of life (QoL) of the participants. The secondary outcomes were results of (1) blood pressure; (2) full lipid profile (3) reliable assessment of anxiety and depression in patients. RESULTS: All studies were conducted between 2013 and 2022, and a total of 5 articles could be included in the quantitative meta-analysis. The results showed that there was a statistically significant difference between the HBCTR intervention group and the control group in 6WMT (MD 16.59, 95%CI 7.13 to 26.06, P = 0.0006), but there was no difference in QoL (SMD - 0.25, 95%CI - 1.63 to 1.13, P = 0.73). According to the fixed effects model, there was a statistically significant difference between the HBCTR group versus the control group (MD - 2.88, 95%CI - 5.19 to - 0.57, P = 0.01), but not in diastolic blood pressure. Likewise, significant improvements of triglycerides and in low-density lipoprotein cholesterol were observed in HBTCR groups, but no significant differences were observed regarding total cholesterol and high-density lipoprotein cholesterol. CONCLUSION: This systematic review and meta-analysis have proven that the HBCTR is one of the promisingly effective cardiac rehabilitation strategies that improve cardiorespiratory fitness and reduce cardiovascular disease risk factors. With the continuous improvement of the telerehabilitation network, it is expected to serve in clinical.

EWI2 prevents EGFR from clustering and endocytosis to reduce tumor cell movement and proliferation.

EWI2 is a transmembrane immunoglobulin superfamily (IgSF) protein that physically associates with tetraspanins and integrins. It inhibits cancer cells by influencing the interactions among membrane molecules including the tetraspanins and integrins. The present study revealed that, upon EWI2 silencing or ablation, the elevated movement and proliferation of cancer cells in vitro and increased cancer metastatic potential and malignancy in vivo are associated with (i) increases in clustering, endocytosis, and then activation of EGFR and (ii) enhancement of Erk MAP kinase signaling. These changes in signaling make cancer cells (i) undergo partial epithelial-to-mesenchymal (EMT) for more tumor progression and (ii) proliferate faster for better tumor formation. Inhibition of EGFR or Erk kinase can abrogate the cancer cell phenotypes resulting from EWI2 removal. Thus, to inhibit cancer cells, EWI2 prevents EGFR from clustering and endocytosis to restrain its activation and signaling.

Effectiveness of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for incomplete spinal cord injury: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for people with incomplete spinal cord injury. METHODS: PubMed, Embase, Web of Science, PEDro, CENTRAL and CINAHL were searched from inception until September 4, 2022. Randomized controlled trials that evaluated the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury were selected. Mean differences (MD) with 95% confidence interval (CI) were calculated. The methodological quality was evaluated by the Cochrane Risk of Bias 2.0 tool. Subgroup analyses were conducted according to the time since injury. RESULTS: In total 19 studies involving 770 patients were eligible for analysis. Individuals with acute incomplete spinal cord injury in robotic-assisted gait training groups showed significantly greater improvements in 6-minute walking test (MD 53.32; 95% CI 33.49 to 73.15; P < 0.001), lower extremity motor scale (MD 5.22; 95% CI 3.63 to 6.80; P < 0.001) and walking index for spinal cord injury II (MD 3.18; 95% CI 1.34 to 5.02; P < 0.001). Robotic-assisted gait training improved peak oxygen consumption to a greater degree for chronic incomplete spinal cord injury patients (MD 4.90; 95% CI 0.96 to 8.84; P = 0.01). CONCLUSION: Robot-assisted gait training may be a feasible and effective intervention in terms of cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury.

CD44 promotes angiogenesis in myocardial infarction through regulating plasma exosome uptake and further enhancing FGFR2 signaling transduction.

BACKGROUND: Since angiogenesis occurs as the pathological process following myocardial infarction to alleviate ischemia, therapeutic angiogenesis has been proposed to be a cardioprotective strategy. CD44 has been implicated in endothelial cell functions and its role has been well established in angiogenesis for years. Although recent studies indicate the close correlation between CD44 and exosome, as well as the two being implicated in myocardial ischemia pathological processes, the effect and the underlying mechanism of CD44 and its regulated plasma exosome in pathological angiogenesis post-myocardial infarction have not been fully elucidated. METHODS: In this study, we used CD44 knockout mice to study the in vivo impacts of CD44 on ischemic angiogenesis in myocardial infarction. Mouse cardiac function was measured by echocardiography, histological changes were observed by Evans Blue and TTC-double staining and Masson's trichrome staining, and molecular changes were detected by immunofluorescence. In the in vitro study, CD44 knockout HUVECs were generated and CD44 inhibitor was used to study the mechanism of CD44 on angiogenesis. We performed the immunoprecipitation, proximity ligation assay, and super-resolution imaging to study the mechanistic regulation of FGFR2 signaling transduction by CD44. Importantly, we also isolated plasma exosomes from myocardial infarction model mice and studied the effect of plasma exosomes on the activation of the FGFR2 signaling pathway and the related phenotypic alterations, including exosomes uptake and angiogenic function in primary mouse microvascular endothelial cells, and further discovered the regulation mechanism of exosomal miRNAs. RESULTS: We observed that the expression of CD44 in the border zone of the infarcted heart was tightly related to pathological angiogenesis following myocardial ischemia. The depletion of CD44 impaired angiogenesis and impacts biogenesis and proangiogenic function of plasma exosomes. Subsequently, we found that CD44 mediated the activation of the FGFR2 signaling pathway as well as the caveolin 1-dependent uptake of exosomes in vascular endothelial cells. Most importantly, the proangiogenic therapeutic effect of plasma exosomal miRNAs depended upon the participation of CD44/FGFR2 signaling transduction in vascular endothelial cells. CONCLUSION: CD44 and its regulated plasma exosomes have crucial potent angiogenic activity. Our studies elucidate that CD44 plays a key role in plasma exosomal miRNA-enhanced angiogenic FGFR2 singling transduction and ischemic angiogenesis in the early stage of myocardial infarction.

What conservative interventions can improve the long-term quality of life, depression, and anxiety of individuals with stable COPD? A systematic review and meta-analysis.

PURPOSE: Many conservative interventions are used in the management of stable chronic obstructive pulmonary disease (COPD). It could be helpful for the prescribers to know what the evidence suggests about the effects of these interventions on the long-term quality of life (QoL), depression, and anxiety. This study aimed to summarize the rationale for the use of conservative interventions to improve the long-term QoL, depression, and anxiety in patients with stable COPD. METHODS: The MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched from database inception to December 2019. Randomized clinical trials (RCTs) investigating the long-term effects of conservative interventions on three parameters, including QoL, depression, and anxiety in patients with COPD were eligible for further analysis. To improve methodological rigor, only RCTs examining these parameters as primary outcomes were included. The standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated using random effects models. Quality of evidence was rated using the updated version of Van Tulder's criteria. RESULTS: Thirty-eight RCTs were identified. Regarding long-term depression, there was moderate evidence supporting cognitive behavioral therapy compared with usual care in patients with COPD; regarding the long-term QoL of patients with COPD, there was limited evidence supporting walking programs, supplementary sugarcane bagasse dietary fiber, roflumilast, and tiotropium. CONCLUSIONS: Cognitive behavioral therapy is effective in alleviating the long-term depression of patients with COPD. Evidence for other interventions was insufficient, making it difficult to draw conclusions in terms of their effectiveness on the long-term QoL, depression, and anxiety.

Influence of age on the association between the triglyceride-glucose index and all-cause mortality in patients with cardiovascular diseases.

BACKGROUND: In patients with cardiovascular diseases, it is reported that the triglyceride-glucose index (TGI) potentially indicates prognosis. However, the results are controversial. Moreover, whether age has an impact on the predictive value of TGI remains unclear. METHODS: Participants with cardiovascular diseases were enrolled using the China Health and Retirement Longitudinal Study (CHARLS) registry. TGI was calculated as ln (triglyceride×glucose/2). The survival status was recorded every 2 years in the follow-up waves. Multivariate regression analysis was carried out to determine the relationship between TGI levels and long-term all-cause mortality in patients grouped by different age. Patients younger than 65 years old were regarded as middle-aged group. Otherwise, they were classified as old group. RESULTS: In total, 2923 patients with cardiovascular diseases and baseline blood test results were included. After 7 years of follow-up, 242 (8.91%) patients died. Cox regression analysis revealed that higher TGI levels were associated with a higher risk of long-term all-cause mortality in middle-aged participants (hazard ratio [HR], 3.64; 95% confidence interval [CI] 1.44-9.22, P = 0.006) but not in old participants (HR 1.20, 95% CI 0.62-2.32, P = 0.594, P for interaction = 0.017), after adjusting physical activity and other factors. Kaplan-Meier estimate analysis and restricted cubic spline curves showed similar results. CONCLUSION: TGI was a promising marker for predicting all-cause mortality in middle-aged patients after cardiovascular diseases. Patients younger than 65 years old who have a higher level of TGI may develop a higher risk of all-cause mortality, and they are encouraged to control vascular risk factors and take more physical activity to improve their prognosis. Additionally, whether intervention in regulating TGI levels is beneficial for the prognosis of these patients needs further investigation.

Efficacy of pulsed electromagnetic field on pain and physical function in patients with low back pain: A systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of pulsed electromagnetic field (PEMF) on pain and physical function in patients with low back pain. DATA SOURCES: A search of PubMed, Embase, Cochrane Library, and Web of Science was conducted up to December 2021. METHODS: We included randomized controlled trials that investigated the effectiveness of PEMF in patients with low back pain. The primary outcome was pain intensity and the secondary outcome was physical function, both were evaluated by assessment scales. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the summary statistics analysis. The registration number of this systematic review in PROSPERO is CRD42020213829. RESULTS: Fourteen trials involving 618 participants were included. The PEMF treatment showed more significant pain alleviation than placebo or other therapy alone in patients with low back pain (SMD = -1.01, 95% CI -1.42 to -0.6, P < 0.001, I2 = 31%; SMD = -0.36, 95% CI -0.62 to -0.11, P = 0.005, I2 = 37%, respectively.) In addition, a significant difference in pain alleviation was observed in patients with chronic low back pain (SMD = -0.6, 95%CI - 0.94 to -0.25, p < 0.001, I2 = 67%), whereas no significant difference was observed in patients with acute low back pain (SMD = -0.46, 95%CI - 0.99 to 0.07, p = 0.09, I2 = 0%). PEMF did not improve physical function compared with the control treatment (SMD = -0.45, 95% CI - 0.98 to 0.07, p = 0.09, I2 = 86%). CONCLUSION: PEMF is beneficial for alleviating pain in patients with chronic low back pain despite having no advantage in improving physical function.

The role of CD44 in pathological angiogenesis.

Angiogenesis is required for normal development and occurs as a pathological step in a variety of disease settings, such as cancer, ocular diseases, and ischemia. Recent studies have revealed the role of CD44, a widely expressed cell surface adhesion molecule, in promoting pathological angiogenesis and the development of its associated diseases through its regulation of diverse function of endothelial cells, such as proliferation, migration, adhesion, invasion, and communication with the microenvironment. Conversely, the absence of CD44 expression or inhibition of its function impairs pathological angiogenesis and disease progression. Here, we summarize the current understanding of the roles of CD44 in pathological angiogenesis and the underlying cellular and molecular mechanisms.

Effects of Abdominal Binders on Postoperative Pain and Functional Recovery: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to assess the effectiveness of abdominal binders (ABs) on postoperative pain and functional recovery in patients receiving abdominal surgery. METHODS: The Pubmed, Embase, Cochrane Library, and PEDro databases were searched for clinical trials published up to November 30, 2019. Randomized controlled trials that compared the effects of wearing an AB to not wearing an AB in participants after abdominal surgery were included. The primary outcomes were pain, pulmonary function, and physical function, as assessed by the visual analog scale score, a spirometry device, and the 6-minute walk test, respectively. The registration number of this review in PROSPERO is CRD42020165303. RESULTS: Fourteen trials involving 1,317 participants were included. Pooled estimates for the visual analog scale score and the 6-minute walk test showed significant differences between the AB group and the control group, especially on the fourth day following surgery (mean difference [MD] = -2.82, 95% confidence interval [CI] = -3.41 to -2.22; P < 0.00001; MD = 50.97 meters, 95% CI = 39.99-61.95 m; P < 0.00001). However, no significant differences were found in pulmonary function (forced vital capacity [FVC]: MD = 0.01, 95% CI = -0.29 to -0.32; P = 0.94; forced expiratory volume during the first second [FEV1]: MD = -0.05, 95% CI = -0.24 to 0.14; P = 0.63; FEV1/FVC: MD = 3.14, 95% CI = -2.78 to 9.06; P = 0.30). CONCLUSION: ABs probably improve postoperative pain and physical function, especially on the fourth day or more following abdominal surgery, but they have no effects on pulmonary function.

The Effect of Pulsed Electromagnetic Fields on Angiogenesis.

A pulsed electromagnetic field (PEMF) has been used to treat inflammation-based diseases such as osteoporosis, neurological injury, and osteoarthritis. Numerous animal experiments and in vitro studies have shown that PEMF may affect angiogenesis. For ischemic diseases, in theory, blood flow may be richer by increasing the number of blood vessels which supply blood to ischemic tissue. PEMF plays a role in enhancing angiogenesis, and their clinical application may go far beyond the current scope. In this review, we analyzed and summarized the effects and possible mechanisms of PEMF on angiogenesis. Most studies have shown that PEMF with specific parameters can promote angiogenesis, which is manifested by an increased vascular growth rate and increased capillary density. The potential mechanisms consist of promoting vascular endothelial cell proliferation, migration, and tube formation, and increasing the expression level of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), angiopoietin-2 (Ang-2), and other angiogenic growth factors. Additionally, PEMF has an impact on the activation of voltage-gated calcium channels (VGCC). Bioelectromagnetics. © 2021 Bioelectromagnetics Society.

Pulsed Electromagnetic Fields Increase Angiogenesis and Improve Cardiac Function After Myocardial Ischemia in Mice.

BACKGROUND: Previous studies have shown that pulsed electromagnetic fields (PEMF) stimulate angiogenesis and may be a potential treatment strategy to improve cardiac function after myocardial infarction (MI). This study explored the effects and its related mechanisms of PEMF in MI mice.Methods and Results:MI mice were used in PEMF treatment (15 Hz 1.5 mT PEMF or 30 Hz 3.0 mT PEMF) for 45 min per day for 2 weeks. Furthermore, an in vivo Matrigel plug assay was used to observe the effect of PEMF in promoting angiogenesis. Compared with the sham PEMF group, PEMF treatment with 30 Hz 3.0 mT significantly improved heart function. PEMF treatment with 15 Hz 1.5 mT and 30 Hz 3.0 mT both increased capillary density, decreased infarction area size, increased the protein expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), Ser473-phosphorylated Akt (pSer473-Akt) and S1177-phosphorylated endothelial nitric oxide synthase (pS1177-eNOS), and increased the mRNA level of VEGF and hypoxia inducible factor 1-alpha (HIF-1α) in the infarct border zone. Additionally, treatment with 30 Hz 3.0 mT also increased protein and mRNA level of fibroblast growth factor 2 (FGF2), and protein level of ß1 integrin, and shows a stronger therapeutic effect. CONCLUSIONS: PEMF treatment could promote angiogenesis of the infarct border zone and improve cardiac function in MI mice. A treatment parameter of 30 Hz 3.0 mT is remarkably effective in MI mice. The effect is associated with the proangiogenic signaling pathways of HIF-1α/VEGF/Akt/eNOS or HIF-1α/FGF2/Akt/eNOS.

Efficacy of Extracorporeal Shockwave Therapy on Pain and Function in Myofascial Pain Syndrome of the Trapezius: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effect of extracorporeal shockwave therapy (ESWT) on pain and function in myofascial pain syndrome (MPS) of the trapezius. DATA SOURCES: PubMed, EMBASE, Web of Science, Physiotherapy Evidence Database, and The Cochrane Central Register of Controlled Trials were systematically searched from the time of their inception to September 2019. STUDY SELECTION: Randomized controlled trials comparing the effects of ESWT on MPS of the trapezius were included in this review. DATA EXTRACTION: Data related to study participants, intervention, follow-up period, measure time, and outcomes were extracted. The Physiotherapy Evidence Database scale and the Cochrane Collaboration Tool for Assessing Risk of Bias were used to assess study quality and risk of bias. DATA SYNTHESIS: In total, 10 articles (n=477 patients) met our criteria and were included in this study. The overall effectiveness was calculated using a meta-analysis method. The meta-analysis revealed that ESWT exhibited significant improvement in pain reduction compared with sham ESWT or ultrasound treatment, but no significant effect when compared with conventional treatments (dry needling, trigger point injection, laser therapy) as for pain intensity and neck disability index. CONCLUSIONS: ESWT appears to benefit patients with MPS of the trapezius by alleviating pain. ESWT may not be an ideal therapeutic method to replace conventional therapies but could serve as an adjunct therapeutic method to those treatments.

Effectiveness of Pulsed Electromagnetic Fields on Bone Healing: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The effect of pulsed electromagnetic field (PEMF) on bone healing is still uncertain and it has not been established as a standardized treatment. The aim of this systematic review and meta-analysis is to evaluate the effect of PEMF on bone healing in patients with fracture. We searched CNKI, Wan Fang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database, and Open Grey websites for randomized controlled trials (published before July 2019 in English or Chinese) comparing any form of PEMF to sham. Reference lists were also searched. Related data were extracted by two investigators independently. The bias risk of the articles and the evidence strength of the outcomes were evaluated. Twenty-two studies were eligible and included in our analysis (n = 1,468 participants). The pooled results of 14 studies (n = 1,131 participants) demonstrated that healing rate in PEMF group was 79.7% (443/556), and that in the control group was 64.3% (370/575). PEMF increased healing rate (RR = 1.22; 95% confidence interval [CI] = 1.10-1.35; I2 = 48%) by the Mantel-Haenszel analysis, relieved pain (standardized mean difference (SMD) = -0.49; 95% CI = -0.88 to -0.10; I2 = 60%) by the inverse variance analysis, and accelerated healing time (SMD = -1.01; 95% CI = -2.01 to -0.00; I2 = 90%) by the inverse variance analysis. Moderate quality evidence suggested that PEMF increased healing rate and relieved pain of fracture, and very low-quality evidence showed that PEMF accelerated healing time. Larger and higher quality randomized controlled trials and pre-clinical studies of optimal frequency, amplitude, and duration parameters are needed. © 2020 Bioelectromagnetics Society.

Correction to: Tetraspanin-enriched microdomains regulate digitation junctions.

In the original publication, abstract text, one of the co-author's name and the legend to Table 1 were incorrectly published.

Tetraspanin-enriched microdomains regulate digitation junctions.

Tetraspanins co-emerged with multi-cellular organisms during evolution and are typically localized at the cell­cell interface, [corrected] and form tetraspanin-enriched microdomains (TEMs) by associating with each other and other membrane molecules. Tetraspanins affect various biological functions, but how tetraspanins engage in multi-faceted functions at the cellular level is largely unknown. When cells interact, the membrane microextrusions at the cell-cell interfaces form dynamic, digit-like structures between cells, which we term digitation junctions (DJs). We found that (1) tetraspanins CD9, CD81, and CD82 and (2) TEM-associated molecules integrin α3ß1, CD44, EWI2/PGRL, and PI-4P are present in DJs of epithelial, endothelial, and cancer cells. Tetraspanins and their associated molecules also regulate the formation and development of DJs. Moreover, (1) actin cytoskeleton, RhoA, and actomyosin activities and (2) growth factor receptor-Src-MAP kinase signaling, but not PI-3 kinase, regulate DJs. Finally, we showed that DJs consist of various forms in different cells. Thus, DJs are common, interactive structures between cells, and likely affect cell adhesion, migration, and communication. TEMs probably modulate various cell functions through DJs. Our findings highlight that DJ morphogenesis reflects the transition between cell-matrix adhesion and cell-cell adhesion and involves both cell-cell and cell-matrix adhesion molecules.

CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells.

BACKGROUND: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from inflammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown. METHODS AND RESULTS: Angiogenesis was examined in Cd82-null mice with in vivo and ex vivo morphogenesis assays. Cellular functions, molecular interactions, and signaling were analyzed in Cd82-null ECs. Angiogenic responses to various stimuli became markedly increased upon Cd82 ablation. Major changes in Cd82-null ECs were enhanced migration and invasion, likely resulting from the upregulated expression of cell adhesion molecules such as CD44 and integrins at the cell surface and subsequently elevated outside-in signaling. Gangliosides, lipid raft clustering, and CD44-membrane microdomain interactions were increased in the plasma membrane of Cd82-null ECs, leading to less clathrin-independent endocytosis and then more surface presence of CD44. CONCLUSIONS: Our study reveals that CD82 restrains pathological angiogenesis by inhibiting EC movement, that lipid raft clustering and cell adhesion molecule trafficking modulate angiogenic potential, that transmembrane protein modulates lipid rafts, and that the perturbation of CD82-ganglioside-CD44 signaling attenuates pathological angiogenesis.

The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk.

Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated.