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BACKGROUND: Brain plasticity and functional reorganization are the main mechanisms of stroke rehabilitation and the theoretical basis for transcranial magnetic therapy. Bimodal balance recovery model suggests that the structural integrity of neural pathways affects the functional reorganization mode of brain recovery after stroke. The principal neural pathway that innervates swallowing is the corticobulbar tract (CBT). The goal is to investigate the impact of corticobulbar tract integrity on swallowing function recovery in post-stroke dysphagia (PSD) patients treated with repetitive transcranial magnetic stimulation (rTMS). METHODS: Thirty-five patients with high CBT integrity (relative fractional anisotropy (rFA) >0.5) and 32 patients with low CBT integrity (rFA ≤0.5) were respectively assigned to three subgroups through a random number table: 5 Hz frequency rTMS group, 1 Hz frequency rTMS group, and Sham rTMS group. The Standardized Swallowing Assessment (SSA), Penetration Aspiration Scale (PAS), and Dysphagia Outcome Severity Scale (DOSS) were analyzed before and after therapy. RESULTS: Significant improvements in SSA (p < 0.05), PAS (p < 0.05), and DOSS scores (p < 0.05) were seen in the high frequency (HF) and low frequency (LF) groups compared with the Sham group for patients with high CBT integrity. Increased SSA (p < 0.05), PAS (p < 0.05), and DOSS scores (p < 0.05) demonstrated that the HF group achieved greater remediation than the LF and Sham groups for patients with low CBT integrity. CONCLUSIONS: Both 5 Hz and 1 Hz rTMS over the contralateral hemisphere are effective for the treatment of swallowing disorders for patients with high CBT integrity after stroke; 5 Hz rTMS over the contralateral hemisphere is more effective than 1 Hz and sham stimulation for patients with low CBT integrity.
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Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Projetos Piloto , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
BACKGROUND: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. METHODS: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. RESULTS: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. CONCLUSIONS: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Tratos Piramidais , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana , Resultado do Tratamento , Extremidade SuperiorRESUMO
Osteoporosis leads to increased bone fragility and risk of fractures. Different strategies have been employed to reduce bone loss, including the use of a pulsed electromagnetic field (PEMF). Although many experimental studies have demonstrated the effect of PEMF on reduction of bone loss, the outcomes studied are varied and insufficient, and the quality of evidence is unknown. Therefore, the aim of this review was to assess the preclinical evidence on the effect of PEMF on bone loss. The existing challenges were also evaluated, and suggestions were provided to strengthen the quality of evidence in future studies. All original articles concerning the effect of PEMF on osteoporosis in animal models were included. Twenty-four studies met the inclusion criteria, 23 of which suggested that PEMF was effective in reducing bone loss, while one study failed to demonstrate any benefit. Risk of bias analysis suggested that information on key measures to reduce bias was frequently not reported. Animal models for osteoporosis, PEMF intervention regimens, outcomes, and specific bone detection sites seemed to influence the efficacy of PEMF in osteoporosis. Our results indicate the potential benefits of PEMF selection in animal models of osteoporosis. However, due to the heterogeneity of the parameters and the quality of the included literature, comprehensive studies using standardized protocols are warranted to confirm the results. © 2021 Bioelectromagnetics Society.
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Doenças Ósseas Metabólicas , Osteoporose , Animais , Doenças Ósseas Metabólicas/terapia , Osso e Ossos , Campos Eletromagnéticos , Osteoporose/terapia , RoedoresRESUMO
Postmenopausal osteoporosis (PMOP) is considered to be a well-defined subject that has caused high morbidity and mortality. In elderly women diagnosed with PMOP, low bone mass and fragile bone strength have been proven to significantly increase risk of fragility fractures. Currently, various anabolic and anti-resorptive therapies have been employed in an attempt to retain healthy bone mass and strength. Pulsed electromagnetic fields (PEMFs), first applied in treating patients with delayed fracture healing and nonunions, may turn out to be another potential and effective therapy for PMOP. PEMFs can enhance osteoblastogenesis and inhibit osteoclastogenesis, thus contributing to an increase in bone mass and strength. However, accurate mechanisms of the positive effects of PEMFs on PMOP remain to be further elucidated. This review attempts to summarize recent advances of PEMFs in treating PMOP based on clinical trials, and animal and cellular studies. Possible mechanisms are also introduced, and the future possibility of application of PEMFs on PMOP are further explored and discussed. Bioelectromagnetics. 38:406-424, 2017. © 2017 Wiley Periodicals, Inc.
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Magnetoterapia/métodos , Osteoporose Pós-Menopausa/terapia , Biomarcadores/metabolismo , Densidade Óssea/efeitos da radiação , Remodelação Óssea/efeitos da radiação , Humanos , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of short-wave therapy with sham or no intervention for the management of patients with knee osteoarthritis. METHODS: We searched the following databases from their inception up to 26 October 2016: MEDLINE, CENTRAL, EMBASE, Physiotherapy Evidence Database, CINAHL and OpenGrey. Studies included randomized controlled trials compared with a sham or no intervention in patients with knee osteoarthritis. The results were calculated via standardized mean difference (SMD) and risk ratio for continuous variables outcomes as well as dichotomous variables, respectively. Heterogeneity was explored by the I2 test and inverse-variance random effects analysis was applied to all studies. RESULTS: Eight trials (542 patients) met the inclusion criteria. The effect of short-wave therapy on pain was found positive (SMD, -0.53; 95% CI, -0.84 to -0.21). The pain subgroup showed that patients received pulse modality achieved clinical improvement (SMD, -0.83; 95% CI, -1.14 to -0.52) and the pain scale in female patients decreased (SMD, -0.53; 95% CI, -0.98 to -0.08). In terms of extensor strength, short-wave therapy was superior to the control group ( p < 0.05, I2 = 0%). There was no significant difference in the physical function (SMD, -0.16; 95% CI, -0.36 to 0.05). For adverse effects, there was no significant difference between the treatment and control group. CONCLUSION: Short-wave therapy is beneficial for relieving pain caused by knee osteoarthritis (the pulse modality seems superior to the continuous modality), and knee extensor muscle combining with isokinetic strength. Function is not improved.
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Osteoartrite do Joelho/reabilitação , Manejo da Dor/métodos , Terapia por Ondas Curtas/normas , Humanos , Terapia por Ondas Curtas/métodos , Resultado do TratamentoRESUMO
The purpose of this study was to investigate the efficacy and safety of intra-articular Botulinum Toxin type A (BTA) injection in the management of patients with knee osteoarthritis (KOA). The literature retrieval was conducted based on PRISMA guidelines. Databases including Pubmed, Web of science, EMBASE, and Cochrane Library were searched to identify RCTs that comparing the effects of intra-articular BTA injection with control interventions on patients with KOA. The primary outcomes involved pain and function improvements as well as the occurrence of adverse events. Seven RCTs comprising 548 participants were included in this meta-analysis. Compared with the control group, BTA injection exhibited greater pain reduction at 4 weeks posttreatment (SMD = -0.86, 95% CI [-1.52, -0.19], p = 0.011), but not 8-24 weeks posttreatment (wk 8, SMD = -0.53, 95% CI [-1.21, 0.15], p = 0.127; wk 12, SMD = -0.34, 95% CI [-0.73, 0.04], p = 0.081; wk 24, SMD = -0.65, 95% CI [-1.52, 0.22], p = 0.144). Additionally, no differences were found between BTA injection versus control intervention on functional improvement at all time points assessed (wk 4, WMD = -5.16, 95% CI [-12.31, 2.00], p = 0.158; wk 8, WMD = -0.98, 95% CI [-5.66, 3.71], p = 0.683; wk 12, WMD = -2.52, 95% CI [-7.54, 2.50], p = 0.325); wk 24, WMD = -3.66, 95% CI [-14.09, 6.76], p = 0.491). There was no significant difference in adverse event rate between the BTA and control group (OR = 0.88, 95% CI [0.24, 3.18], p = 0.843). This meta-analysis suggests that intra-articular BTA injection could be an efficious and safe strategy for analgesic treatment of KOA. However, evidence is limited due to the small number and heterogeneity of included studies, this urges further and stronger trials to confirm our findings.
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Toxinas Botulínicas Tipo A , Osteoartrite do Joelho , Humanos , Toxinas Botulínicas Tipo A/toxicidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor/induzido quimicamente , Injeções Intra-ArticularesRESUMO
PURPOSES: To evaluate the effects of low frequency whole-body vibration (WBV) on degeneration of articular cartilage and subchondral bone in mice with destabilization of the medial meniscus (DMM)induced osteoarthritis(OA) and mice with normal knee. METHODS: Ten-week-old C57BL/6J male mice received DMM on right knees, while the left knees performed sham operation. There were six groups: DMM, SHAM DMM, DMM+WBV,SHAM DMM+WBV, DMM+ NON-WBV and SHAM DMM+NON-WBV. After four weeks, the knees were harvested from the DMM and SHAM DMM group. The remaining groups were treated with WBV (10 Hz) or NON-WBV. Four weeks later, the knees were harvested. Genes, containing Aggrecan(Acan) and Collagenâ ¡(Col2a1), Matrix Metalloproteinases 3 and 13(MMP3,13), TNFα and IL6, were measured and staining was also performed. OA was graded with OARSI scores, and tibial plateaubone volume to tissue volume ratio(BV/TV), bone surface area to bone volume ratio (BS/BV), trabecular number(Tb.N) and trabecular thickness separation(TS) between groups were analyzed. RESULTS: Increased OARSI scores and cartilage degradation were observed after WBV. BV/TV, Tb.N and TS were not significant between the groups. Significant reductions were observed in MMP3, MMP13, Col2a1, Acan, TNFα and IL6 in the DMM+WBV compared to SHAM DMM+WBV group. BV/TV, BS/BV, Tb.N, TS and OARSI scores were not significantly changed in the left knees. IL6 expression in the SHAM DMM+WBV group was significantly increased compared with the SHAM DMM+ NON-WBV group, while Col2a1, Acan and MMP13 expression decreased. CONCLUSION: WBV accelerated cartilage degeneration and caused slight changes in subchondral bone in a DMM-induced OA model. WBV had no morphologic effect on normal joints.
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Cartilagem Articular , Osteoartrite do Joelho , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite do Joelho/terapia , Fator de Necrose Tumoral alfa , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz , Interleucina-6/genética , Vibração/uso terapêuticoRESUMO
CONTEXT: Noninvasive brain stimulations (NIBS) have been increasingly applied to the patients with neuropathic pain (NP), while the effectiveness of NIBS in the management of NP is still conflicting. OBJECTIVES: To examine the effectiveness of NIBS on pain and depression symptoms of patients with NP. METHODS: A comprehensive literature retrieval was performed on MEDLINE, Embase, PsycINFO, PEDro, and CENTRAL from the establishment of the databases to June 2021. Randomized controlled trials comparing NIBS with sham stimulation were included. RESULTS: A total of thirteen trials comprising 498 participants met the inclusion criteria. The pooled analysis found a significant effect on the improvement of pain scores at post-treatment, favoring NIBS over sham stimulation (SMDâ¯=â¯-0.60; 95% CI: -1.00 to -0.20; Pâ¯=â¯0.004). Subgroup analysis showed that only transcranial direct current stimulation (tDCS) (SMDâ¯=â¯-0.38; 95% CI: -0.71 to -0.04; Pâ¯=â¯0.030) and high-frequency repetitive transcranial magnetic stimulation (H-rTMS) (SMDâ¯=â¯-0.95; 95% CI: -1.85 to -0.04; Pâ¯=â¯0.040) had positive effects on pain reduction among all types of NIBS. The favorable effects of NIBS remained significant at follow-up visit (SMDâ¯=â¯-0.51; 95% CI: -0.79 to -0.23; Pâ¯=â¯0.000), while only H-rTMS was found in subgroup analyses to significantly improve pain scales of the patients (SMDâ¯=â¯-0.54; 95% CI: -0.85 to -0.24; Pâ¯=â¯0.000). Additionally, overall NIBS showed no beneficial effect over sham stimulation in reducing depression symptoms of NP patients either at post-treatment (SMDâ¯=â¯-0.19; 95% CI: -0.39 to 0.01; Pâ¯=â¯0.061) or at follow-up visit (SMDâ¯=â¯-0.18; 95% CI: -0.45 to 0.10; Pâ¯=â¯0.202). CONCLUSION: This meta-analysis revealed the analgesic effect of NIBS on patients with NP, while no beneficial effect was observed on reducing concomitant depression symptoms. The findings recommended the clinical application of NIBS in patients with NP.
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Depressão , Neuralgia , Manejo da Dor , Estimulação Transcraniana por Corrente Contínua , Humanos , Analgésicos , Encéfalo , Depressão/terapia , Neuralgia/terapia , Estimulação Magnética Transcraniana , DorRESUMO
The continuous application of chemical fertilizers in vegetable cropping has led to deterioration of the soil environment and reduced yield and quality. The objective of this study was to evaluate the effect of combining chemical and bio-organic fertilizers on cauliflower yield, soil biochemical properties, and the bacterial community. Six treatments were established: no fertilizer (CK, control), chemical fertilizers (CF, conventional dosage for this region), balanced fertilization (BF, 30% reduction of chemical fertilizers), and balanced fertilization plus 3,000, 6,000, or 12,000 kg.ha-1 bio-organic fertilizer (Lvneng Ruiqi Biotechnology Co., Ltd., Gansu, China) (BF + OF1, BF + OF2, BF + OF3, respectively). A two-season field experiment with cauliflower was conducted under the different fertilizer treatments in irrigation districts along the Yellow River, Northwest China. The results indicate that the yield, soil organic matter, total potassium content, and enzyme activity under the bio-organic treatments were generally higher than those under the CF treatment. Compared with the CF treatment, the BF treatment increased soil organic matter content, enzyme activity and soil bacterial relative abundance. Moreover, the bacterial alpha-diversity were higher than those of conventional fertilization. The predominant phyla, including Proteobacteria, Actinobacteria, Gemmatimonadetes, and Chloroflexi, were the main contributors to the microbiome shift, as demonstrated by their remarkable enrichment in the soil under BF + OF2 and BF + OF3 treatments. Furthermore, Pearson correlation analyses show significant correlations among the soil organic matter, available P and K, electrical conductivity, and relative abundance of potentially beneficial microbial groups, such as the genera Massilia, Bacillus, Lysobacter, and Nitrosospira. Overall, this study suggests that balanced fertilization and the application of bio-organic fertilizers are essential to ensure soil fertility and long-term sustainable green productivity.
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BACKGROUND: Immunosuppressive drugs are routinely used to treat myasthenia gravis (MG). However, current recommendations provide limited evidence to support treatment options, leading to considerable variation in practice among healthcare specialists. Hence, we present a protocol for a systematic review and network meta-analysis (NMA) to update the evidence by comparing the efficacy and acceptability of oral immunosuppressive drugs for the treatment of MG. METHODS: We will conduct a systematic review and NMA of all randomized controlled trials evaluating the following oral immunosuppressive drugs for the treatment of MG. Published studies will be searched using the following databases from inception to November 23, 2021: CENTRAL, the CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, and 3 Chinese databases (Chinese Biomedical Literatures Database, CNKI, and Wan Fang database). Assessment of study eligibility and data extraction will be conducted independently by 2 reviewers. The main outcome will be a quantitative MG scoring system. We will conduct Bayesian NMA to synthesize all evidence for each outcome and obtain a comprehensive ranking of all treatments. The quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: The objective of this study was to assess the relative clinical efficacy and acceptability of first-line immunosuppressants for the treatment of MG, using a systematic review and NMA approach. CONCLUSION: In the absence of head-to-head trials comparing therapies, evidence from this NMA of available clinical trials will inform clinicians, patients, and families the risk-benefit profiles of different treatment options.
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Imunossupressores , Miastenia Gravis , Humanos , Imunossupressores/uso terapêutico , Metanálise em Rede , Teorema de Bayes , Resultado do Tratamento , Miastenia Gravis/tratamento farmacológico , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
Chronic inflammatory pain is a serious clinical problem caused by inflammation of the joints and degenerative diseases and greatly affects patients' quality of life. Persistent pain states are thought to result from the central sensitization of nociceptive pathways in the spinal dorsal horn. Spinal microglia-mediated neuroinflammation plays a pivotal role in the development and maintenance of the central sensitization of chronic inflammatory pain. Botulinum toxin type A (BoNT/A) was recently reported to have analgesic and anti-inflammatory effects. However, the precise mechanism underlying its analgesic effect remains unclear. Although several studies have reported that BoNT/A could regulate neuroflammation, the reduction of neuroinflammation regulated by BoNT/A in chronic inflammatory pain in experimentally induced arthritis has not been reported. The aim of this study was to investigate whether BoNT/A could alleviate adjuvant-arthritis pain via modulating microglia-mediated neuroinflammation and intracellular molecular pathway. The pain behavioral tests were performed before and after CFA immunization as well as after BoNT/A injection. Western blotting and immunofluorescence staining were used to assess the changes of microglial activation markers (ionized calcium binding adaptor molecule 1, IBA-1) and phosphorylation of P38MAPK (P-p38MAPK) in the lumbar spinal cord. TNF-αand P2X4R gene expression were studied by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that (1) the activation of spinal microglia can be continued till 21 days after CFA injection, which suggested its role in the development and maintenance of chronic inflammatory pain. (2) The intra-articular administration of a single eï¬ective dose of BoNT/A (5U/10 U) on day 21 after CFA injection significantly reduced nociceptive behaviors and decreased protein overexpression and immunoreactivity for IBA-1 and P-p38MAPK in CFA induced rat. Simultaneously, BoNT/A (5 U) also inhibited the increase in TNF-α mRNA and P2X4R mRNA expression induced by CFA injection. These results suggested that BoNT/A is a potential therapeutic agent for relieving the neuroinflammation that occurs in chronic inflammatory pain by inhibiting the activation of microglial cells and the release of microglia-derived TNF-α. This effect is likely mediated by inhibiting the activation of the P2X4R-P38MAPK signaling pathways in spinal microglial cells.
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Artrite Experimental/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Animais , Inflamação/tratamento farmacológico , Masculino , Ratos , Receptores Purinérgicos P2X4/genética , Receptores Purinérgicos P2X4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: The aim of the study was to compare the effectiveness of the integration of orthotic intervention and scoliosis-specific exercise with orthotic intervention only via assessing the spinal deformity, back muscle endurance, and pulmonary function of the patients with adolescent idiopathic scoliosis. DESIGN: It is a prospective randomized controlled study. Patients who fulfilled the SRS criteria for orthotic intervention were randomly assigned to the orthosis combined with exercise group (combined orthotic and exercise intervention) or the orthotic intervention group (orthotic intervention only). All the subjects were prescribed with a rigid thoracolumbosacral orthosis and scoliosis-specific exercise program was provided to the subjects in the orthosis combined with exercise group. Cobb angle, back muscle endurance, and pulmonary function of subjects were measured at baseline, 1-mo, and 6-mo follow-up visits. RESULTS: After 6 mos of intervention, the subjects in the orthosis combined with exercise group showed better Cobb angle correction than those in the orthotic intervention group. The back muscle endurance and pulmonary function decreased in the subjects of the orthotic intervention group, whereas some improvement happened in the subjects of the orthosis combined with exercise group. Between-group statistical significance was detected at the 6-mo follow-up among back muscle endurance time and parameters of pulmonary function. CONCLUSIONS: In this study, orthotic intervention combined with scoliosis-specific exercise offered better Cobb angle correction and improvement of the respiratory parameters and back muscle endurance of the patients with adolescent idiopathic scoliosis as compared with orthotic intervention only.
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Braquetes , Terapia por Exercício , Escoliose/terapia , Adolescente , Músculos do Dorso , Criança , Feminino , Humanos , Masculino , Força Muscular , Estudos Prospectivos , Resultado do Tratamento , Capacidade VitalRESUMO
INTRODUCTION: Exercise is considered as an effective intervention in the management of patients with chronic low back pain (cLBP). However, the relative effectiveness as well as the hierarchy of exercise interventions have not been well established, although various exercise options are available. Therefore, the present protocol proposes to conduct a network meta-analysis (NMA) aiming to evaluate the effectiveness of different forms of exercise for treatment of cLBP. METHODS AND ANALYSIS: Medline, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, and the Physiotherapy Evidence Database will be searched to identify all randomised controlled trials that evaluate the effectiveness of exercise in the treatment of cLBP. There will be no restrictions on date or language. Two authors will screen the literature and extract data independently based on predesigned rules, and evaluate the risk of bias of included studies using the Cochrane Risk of Bias Tool. Disagreements will be resolved through discussion or consultation with a senior reviewer. The primary outcomes of this study will be pain relief and improvement in function or disability for all interventions. Traditional pairwise meta-analysis and Bayesian NMA will be conducted to compare the effectiveness of different exercise interventions. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation instrument. ETHICS AND DISSEMINATION: Ethical approval and informed consent are not required since this is a protocol for a meta-analysis with no confidential personal data to be collected. The results of this NMA will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42018090576.
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Terapia por Exercício/métodos , Dor Lombar/terapia , Teorema de Bayes , Doença Crônica , Humanos , Metanálise em Rede , Modalidades de Fisioterapia , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
INTRODUCTION: Achieving efficacious and safe treatments for unstable angina pectoris (UAP) is still a challenging clinical problem. The availability of different oral Chinese patent medicines frequently poses a practical challenge to clinicians, namely, which one to choose as first-line regimen for treatment. This study aims to examine the comparative effectiveness and safety of oral Chinese patent medicines for UAP on the national essential drugs list of China. METHODS AND ANALYSIS: We will conduct a network meta-analysis (NMA) of all randomised controlled trials to evaluate the use of oral Chinese patent medicines as adjuvant for the treatment of UAP. We will explore eight electronic databases from their inception to June 2018 and search for grey literature. Primary outcomes include mortality and the cardiovascular events. Secondary outcomes include: (1) symptom improvement; (2) ECG improvement; (3) frequency of acute angina attack; (4) duration of angina; (5) adverse effects. Two independent authors will screen titles and abstracts, review full texts, extract data, assess the risk of bias using the Cochrane risk of bias tool and assess the quality of evidence and strength of the recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). If adequate data are available, NMA will be performed with Bayesian analysis methods. ETHICS AND DISSEMINATION: The NMA will help us to reduce the uncertainty of interventions and help clinicians to make optimal and more accurate therapeutic decisions for adults with UAP. Therefore, we will publish the findings of this study in a peer-reviewed journal. No ethics approval is necessary for this study based on the nature of its design. TRIAL REGISTRATION NUMBER: CRD42018092822.
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Angina Instável/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos Essenciais , Adjuvantes Farmacêuticos , Administração Oral , China , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Metanálise como Assunto , Metanálise em Rede , Medicamentos sem Prescrição , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
We examined the effects of tumor necrosis factor-α (TNFα) and interleukin-6 (IL6) gene knockout in preserving the bone loss induced by ovariectomy (OVX) and the mechanisms involved in bone metabolism. Twenty female wild-type (WT), TNFα-knockout (TNFα-/-) or IL6-knockout (IL6-/-) mice aged 12 weeks were sham-operated (SHAM) or subjected to OVX and killed after 4 weeks. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone marrow stromal cells (BMSCs) from all three groups (WT, TNFα-/- and IL6-/-) were induced to differentiate into osteoblasts or osteoclasts and treated with 17-ß-estradiol. Bone metabolism was assessed by histological analysis, serum analyses and qRT-PCR. OVX successfully induced a high turnover in all mice, but a repair effect was observed in TNFα-/- and IL6-/- mice. The ratio of femoral trabecular bone volume to tissue volume, trabecular number and trabecular thickness were significantly decreased in WT mice subjected to OVX, but increased in TNFα-/- mice (1.62, 1.34, 0.27-fold respectively; P < 0.01) and IL6-/- mice (1.34, 0.80, 0.22-fold respectively; P < 0.01). Furthermore, we observed a 29.6% increase in the trabecular number in TNFα-/- mice when compared to the IL6-/- mice. Both, TNFα-/- and IL6-/- BMSCs exhibited decreased numbers of TRAP-positive cells and an increase in ALP-positive cells, with or without E2 treatment (P < 0.05). While the knockout of TNFα or IL6 significantly upregulated mRNA expressions of osteoblast-related genes (Runx2 and Col1a1) and downregulated osteoclast-related mRNA for TRAP, MMP9 and CTSK in vivo and in vitro, TNFα knockout appeared to have roles beyond IL6 knockout in upregulating Col1a1 mRNA expression and downregulating mRNA expressions of WNT-related genes (DKK1 and Sost) and TNF-related activation-induced genes (TRAF6). TNFα seemed to be more potentially invasive in inhibiting bone formation and enhancing TRAF6-mediated osteoclastogenesis than IL6, implying that the regulatory mechanisms of TNFα and IL6 in bone metabolism may be different.