Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Acupuncture as adjunctive therapy for patients with AECOPD: study protocol for a multicenter, randomized controlled trial.

Background: The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations. Methods and analysis: This study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization. Ethics and dissemination: Ethical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.

Recent trends in acupuncture for chronic pain: A bibliometric analysis and review of the literature.

BACKGROUND: Acupuncture has been increasingly used in patients with chronic pain, yet no bibliometric analysis of acupuncture studies for chronic pain exists. OBJECTIVES: To investigate the characteristics, hotspots and frontiers of global scientific output in acupuncture research for chronic pain over the past decade. METHODS: We retrieved publications on acupuncture for chronic pain published from 2011 to 2022 from the Science Citation Index Expanded (SCI-expanded) of the Web of Science Core Collection (WoSCC). The co-occurrence relationships of journals/countries/institutions/authors/keywords were performed using VOSviewer V6.1.2, and CiteSpace V1.6.18 analyzed the clustering and burst analysis of keywords and co-cited references. RESULTS: A total of 1616 articles were retrieved. The results showed that the number of annual publications on acupuncture for chronic pain has increased over time, with the main types of literature being original articles (1091 articles, 67.5 %) and review articles (351 articles, 21.7 %). China had the most publications (598 articles, 37 %), with Beijing University of Traditional Chinese Medicine (93 articles, 5.8 %) and Evidence-based Complementary and Alternative Medicine ranked first (169 articles, 10.45 %) as the most prolific affiliate and journal, respectively. Liang FR was the most productive author (43 articles), and the article published by Vickers Andrew J in 2012 had the highest number of citations (625 citations). Recently, "acupuncture" and "pain" appeared most frequently. The hot topics in acupuncture for chronic pain based on keywords clustering analysis were experimental design, hot diseases, interventions, and mechanism studies. According to burst analysis, the main research frontiers were functional connectivity (FC), depression, and risk. CONCLUSION: This study provides an in-depth perspective on acupuncture for chronic pain studies, revealing pivotal points, research hotspots, and research trends. Valuable ideas are provided for future research activities.

Clinical Evidence for Association of Acupuncture with Improved Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: Depression is the most significant contributor to non-fatal health reductions worldwide. Acupuncture is the most commonly used complementary alternative therapy to relieve major depressive disorder (MDD) effectively. Nevertheless, the effects of acupuncture for MDD are uncertain. This review aimed to determine the efficacy and safety of acupuncture for MDD. METHODS: Meta-analysis was performed for randomized controlled trials of acupuncture for MDD data from eight databases searched from inception until February 10, 2022. All RCTs with adult participants undergoing acupuncture treatment for MDD were included. The primary outcome measure was the Hamilton rating scale for depression (HAMD). We used random-effects meta-analysis to synthesize the results with a mean difference or odds ratio. Furthermore, the potential heterogeneity was tested through meta-regression/subgroup analyses/sensitive analysis. The quality of evidence for each outcome was assessed by the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Forty-three studies were included: 9 acupuncture versus sham acupuncture (n = 920), 26 acupuncture versus antidepressants (n = 2169), and 9 acupuncture plus antidepressants versus antidepressants (n = 667). Of the 43 high-quality articles, 24 and 8 were determined to have a low and moderate risk of bias, respectively. The pooled results for HAMD and SDS revealed the clinical benefits of acupuncture or acupuncture plus antidepressants compared to sham acupuncture or antidepressants, with high-quality evidence. Furthermore, high-quality evidence showed that acupuncture led to fewer adverse effects than antidepressants. CONCLUSIONS: Acupuncture or acupuncture plus antidepressants were significantly associated with reduced HAMD scores, with high-quality evidence. Also, more rigorous trials are needed to identify the optimal frequency of acupuncture for MDD and integrate such evidence into clinical care to reduce antidepressant use.

Effectiveness and Safety of Acupuncture-Related Therapies for Chronic Musculoskeletal Pain: A Protocol for Systematic Review and Network Meta-Analysis.

Introduction: Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain. Methods and Analysis: Our literature search will be performed in five electronic databases-the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results. Results: Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option. Conclusion: This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.

Effectiveness and Safety of Electroacupuncture for Depression: A Systematic Review and Meta-Analysis.

Purpose: The purpose of this systematic review and meta-analysis was to comprehensively evaluate the efficacy and safety of electroacupuncture as an effective adjunctive therapy for patients with depression. Methods: Randomized controlled trials (RCTs) about the treatment of depression by electroacupuncture therapy from inception to September 2021 were searched and collected in eight databases. HAMD, SDS, and Adverse Reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each outcome was assessed through the Grading of Recommendations Assessment and the Development and Evaluation approach. Stata 15.0 software was used for data analysis. Results: A total of 16 depression-related RCTs were included in this meta-analysis. For the main outcome, electroacupuncture significantly reduced HAMD scores (I2:0.0%, SMD: -2.28% (95% CI-3.16 to -1.39)), and the quality of evidence was moderate. The improvement effect of electroacupuncture plus antidepressants was better than that of western drugs in patients with depression (I2:26.2%, SMD: -1.18% (95% CI-1.42 to -0.94)), and the quality of evidence was moderate. Electroacupuncture significantly reduced HAMD scores without significant heterogeneity (I2:0.0%, SMD: -3.76% (95%CI-5.78-1.73)). Studies with very low quality of evidence found that electroacupuncture was as effective as antidepressants in reducing SDS scores (I2:36.4%, WMD: -1.15% (95%CI-2.93-0.63)), and electroacupuncture was found to be more effective than sham electroacupuncture stimulation as well. Moderate quality evidence showed no statistical difference between electroacupuncture plus antidepressants/electroacupuncture and antidepressants (I2:0%, RR:1.05% (95%CI 0.73 to 1.53)). Conclusions: Our meta-analysis shows that electroacupuncture reduces HAMD scores. It is suggested to use electroacupuncture plus antidepressants to improve the curative effect and effectively reduce drug side effects.

The Application of Acupuncture Therapy for Postoperative Pain Over the Past 20 Years: A Bibliometric Analysis.

Purpose: The purpose of this study is to analyze and visualize the research trends on acupuncture therapy for postoperative pain over the past 20 years to identify hotspots and frontiers, and provide new research ideas. Methods: A search of the Web of Science database, with a time frame of 2001-01-01 to 2022-02-28, was conducted to collect literatures related to acupuncture therapy for postoperative pain. A bibliometric analysis and visualization of results was performed using CiteSpace software for the volume of annual publications, journals, countries, institutions, authors, keywords, and references. Results: A total of 840 literatures were eventually included in the analysis. The number of publications has fluctuated upwards each year over the past 20 years and reached a peak in the latest three years. Evidence-Based Complementary and Alternative Medicine was the journal with the most relevant publications and Pain was the most frequently cited journal. The country with the highest volume of publications was China, and the USA contributed most to the international collaboration. The most prolific and influential authors were Inhyunk Ha and Han JS respectively. The most frequent keyword was "acupuncture". References with highest frequency or centrality were both systematic evaluations focusing on different acupuncture therapies for postoperative pain relief. Conclusion: The field of acupuncture therapy for postoperative pain is currently in a period of high growth. China and the USA have made the largest contribution to the volume of publications. The most influential institutions and authors are mainly from China and South Korea. The overall collaborative network needs to be strengthened. Electroacupuncture and auricular acupuncture (therapeutic techniques), low back surgery (types of surgery), and "postoperative pain, nausea and vomiting" are research hotspots in this field. Improvement of postoperative life quality, proof of clinical efficacy and evidence-based evaluation are the current research trends and frontiers.

The dose-effect association between acupuncture sessions and its effects on major depressive disorder: A meta-regression of randomized controlled trials.

BACKGROUND: The benefits of acupuncture on Major depressive disorder (MDD) have been well established in previous studies. However, uncertainty exists regarding the dose-effect relationship between acupuncture and MDD. This study aims to explore the association between acupuncture and its effects on MDD based on previously published data. METHODS: Nine databases were searched from inception until 10th September 2021. Randomized controlled trials that compared acupuncture with sham acupuncture, or anti-depressants, were included. The data extraction, and assessing the data quality and risk of bias completed by two researcher, respectively. A non-linear meta-regression approach with restricted cubic spline was used to investigate the dose-effect relationship between acupuncture sessions and their effects on the Hamilton rating scale for depression (HAMD) score. RESULTS: Of the 20,835 citations screened, 62 studies (2269 patients of MDD) were included. The dose-effect meta-analysis suggested that acupuncture session was associated with a decline in HAMD scores. Overall, an increase in the number of acupuncture sessions received was associated with symptom improvement in MDD patients. After 8 acupuncture sessions, the HAMD score decreased from 17.68 (95% CI: -11.81, -4.80) to 8.30 (95% CI: 14.23-21.13). After 24 acupuncture sessions, a decrease in HAMD scores was observed in 51% of cases (95% CI: 48% to 54%). After 36 acupuncture sessions, the effect of improvement in HAMD scores peaked at 66% of cases (95% CI: 59% to 72%). CONCLUSIONS: A dose-effect relationship was found between the number of acupuncture sessions and HAMD scores. 36 acupuncture sessions were associated with optimal clinical response. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021290143.

Acupuncture for Knee Osteoarthritis: A Systematic Review of Randomized Clinical Trials with Meta-Analyses and Trial Sequential Analyses.

Background: Knee osteoarthritis (KOA) can cause chronic pain and seriously affect the quality of patient lives. The continued emergence of high-quality RCTS requires us to update the quality of evidence. This study aims to evaluate the efficacy of acupuncture for KOA patients and calculate the required information size (RIS) to determine whether further clinical studies are required. Methods: We searched PubMed, Embase, WOS, CBM, CNKI, VIP, WHO ICTRP, ChiCTR, and Grey literature to collect randomized controlled trials (RCTs) of acupuncture for KOA from inception to December 2021. A meta-analysis was performed according to the Cochrane systematic review method by using Review Manager 5.4 and TSA 0.9.5.10 beta, and GRADE was used to evaluate the quality of the evidence. Trial sequential analysis was used to control random errors and calculate the required information size. Results: Eleven RCTs with 2484 patients were included in our meta-analysis, meeting the inclusion criteria for the meta-analysis. The meta-analysis indicated that acupuncture had beneficial effect on knee osteoarthritis in reducing pain [n = 2387; SMD = -0.12, 95% CI (-0.20, -0.04); I 2 = 0%] and improved patients function activities [n = 2408; MD = -1.25, 95% CI (-1.97, -0.53); I 2 = 0%], but true acupuncture showed no significant effect in relieve patient's stiffness [n = 1337; MD = -0.07, 95% CI (-0.30, 0.15); I 2 = 0%]. We pooled the studies which found no significant difference in improving the quality life of mental [n = 1462; SMD = 0.02, 95% CI (-0.23, 0.27); I 2 = 78%] and patients physical health (SF-36 or SF-12) [n = 1745; SMD = 1.01, 95% CI (-0.08, 2.11); I 2 = 0%] compared with sham acupuncture. The pain and function TSA graphs indicated that cumulative Z-curves intersected with the traditional level of statistical favoring acupuncture, and more RCTs will required in the future studies. Conclusion: Acupuncture has beneficial effect on pain relief and improves function activities, and this treatment can be recommended as a beneficial alternative therapy in patients with KOA, particularly for chronic patients and those currently undergoing long-term pain and help them increasing quality of life. But it should be further verified through more RCTs in function. Available studies suggested that acupuncture was superior to sham acupuncture in reduce pain and function as verified by TSA.

Potential efficacious materials investigation of Yi-Yi Mixture based on Metabolome-oriented network pharmacology strategy.

Yi-Yi Mixture, an efficient Chinese medicine preparation composed of four herbal medicines, has been used in clinical practice in China for the treatment of acute pancreatitis over twenty years. However, its functional materials against acute pancreatitis remains unclear, which is a huge obstacle for quality control. In this study, a metabolome-oriented network pharmacology strategy was proposed to clarify its potential substances and further screen out quality markers. Firstly, an Ultra-High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was utilized to profile the chemical constituents in Yi-Yi Mixture. Secondly, metabolic exposure of chemical constituents as well as their global metabolites produced in biological systems were profiled and defined as metabolome of Yi-Yi Mixture. Then, the metabolome targets were predicted based on network analysis. As a result, a total of 66 chemical components were characterized, including 6 stilbenes, 21 anthraquinones, 7 phenols, 13 neolignans, 3 naphthalenes and 16 other types. Moreover, metabolic profiles of YYM (32 prototypes and 37 metabolites) were analyzed in rat bio-samples. Among them, resveratrol, emodin, chrysophanol, rhein and their derivatives were detected in multiple tissues/organs, revealing their potential as key pharmacodynamic substances. These were further confirmed by metabolome-oriented network analysis and molecular docking techniques. This is the first comprehensive investigation on chemical and metabolic profiles of Yi-Yi Mixture, and the results provided scientific foundation for further research on quality control and clinical-safe medication administration.

Bibliometric Analysis of Functional Magnetic Resonance Imaging Studies on Acupuncture Analgesia Over the Past 20 Years.

BACKGROUND: Researches on the central mechanisms of acupuncture analgesia have been widely conducted worldwide. However, there is no bibliometric analysis of functional magnetic resonance imaging (fMRI) studies on acupuncture analgesia. This study visualized the current status, hot spots and frontiers of fMRI studies on acupuncture analgesia in the past 20 years to provide a theoretical basis for its clinical application. METHODS: All publications were obtained from Science Citation Index-Expanded (SCI-E) of Web of Science (WOS). We used CiteSpace to analyze publications, journals, cited journals, authors, cited authors, institutions, countries, references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps. RESULTS: We retrieved a total of 797 articles. Regarding the volume of publications, the total number of annual publications showed a fluctuating but overall increasing trend. Evidence-based Complementary and Alternative Medicine (21 articles) was the most productive journal, and Pain (225 articles) was the most cited journal. The most productive author was Qin W (16 articles), and the most co-cited author was Hui KKS (111). The most prolific institution and country were Massachusetts General Hospital (34 articles) and USA (212 articles). "Pain" was the top-ranked for keyword frequency and centrality. "Functional connectivity" was the frontier hotspot for 2018-2021. CONCLUSION: First, fMRI researches on acupuncture analgesia involved several countries (regions) and institutions, mainly located in the USA, China and Korea, and most of them were universities. In addition, the USA was a major contributor in this field. Second, in terms of disciplinary distribution, the literatures were mainly from clinical neurology, neuroscience, and radiology nuclear medicine medical imaging. Third, the keyword co-occurrence analysis showed that the hot keywords included pain, fMRI, and lower back pain. Fourth, through keyword clustering analysis, the hot disease was found to be lower back pain, and the hot contents were acupuncture specificity and frequency specificity. Fifth, a timeline analysis of the references identified that chronic low back pain and specificity will remain a hot topic for future research.

Acupuncture for Quality of Life of Patients with Defecation Dysfunction after Sphincter Preserving Surgery for Rectal Cancer: A Systematic Review.

PURPOSE: To evaluate the effectiveness and safety of acupuncture for quality of life of patients with defecation dysfunction (DD) after sphincter preserving surgery for rectal cancer. METHODS: We searched nine online databases from inception to July 1, 2021, and did not restrict the type of language. Then, studies were independently selected by two research team members with screening criteria and risk bias assessment, and the data were extracted. The primary outcome was Quality of Life Questionnaire-Core 29 (QLQ-CR29). The data were then synthesized using the RevMan V.5.2 by random-effects model. Also, we used the standardized mean differences with 95% credible interval (CI) to describe the outcome of the analysis. RESULTS: A total of 6 randomized controlled trials (RCTs) (with 439 patients) were included in the systematic review, and data from 2 RCTs (with 200 patients) were used in the meta-analysis. Five studies (83%) were judged to have a medium risk of bias, and one was at high risk of bias. For synthesis, data from two medium-risk studies found that acupuncture or electropuncture may improve the QLQ-CR29 with urination (mean difference, -0.39 points; 95%CI, -0.46 to -0.32; I 2 = 34%), abdominal pain (mean difference, -0.71 points; 95%CI, -0.89 to -0.54; I 2 = 9%), stool (mean difference, -0.49 points; 95%CI, -0.77 to -0.20; I 2 = 57%), defecation (mean difference, -0.59 points; 95% CI, -0.85 to -0.33; I 2 = 51%), sexual function (mean difference, 0.93 points; 95% CI, 0.48 to 1.38; I 2 = 90%), and self-feelings (mean difference, 1.04 points; 95% CI, 0.36 to 1.73; I 2 = 94%). CONCLUSION: Findings in this study indicate that acupuncture or electropuncture may be effective and safe for DD, but the quality of included studies was very low. So, more large-scale, multicenter, long-term, and high-quality original research is still expected in the future.

Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience.

BACKGROUNDS: Pilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs. METHODS: All patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail. RESULTS: Finally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation. CONCLUSION: Although the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.

Structural dependence of antidiabetic effect of steviol glycosides and their metabolites on streptozotocin-induced diabetic mice.

BACKGROUND: Stevia has been proposed as a potential antidiabetic sweetener, mainly based on inconsistent results from stevioside or the plant extract, yet lacking relative experimental evidence from individual steviol glycosides (SGs) and their metabolites. RESULTS: The results systematically revealed that the typical SGs and their final metabolite (steviol) presented an antidiabetic effect on streptozotocin (STZ) diabetic mice in all assayed antidiabetic aspects. In general, the performance strength of the samples followed the sequence steviol > steviol glucosyl ester > steviolbioside > rubusoside > stevioside > rebaudioside A, which is opposite to their sweetness strength order, and generally in accordance with the glucosyl group numbers in their molecules. This may imply that the antidiabetic effect of the SGs might be achieved through steviol, which presented antidiabetic performance similar to that of metformin with a dose of 1/20 that of metformin. Moreover, the 18 F-fluorodeoxyglucose traced micro-PET experiment revealed that stevioside and steviol could increase the uptake of glucose in the myocardium and brain of the diabetic mice within 60 min, and decrease the accumulation of glucose in the liver and kidney. CONCLUSIONS: The SGs and steviol presented an antidiabetic effect on STZ diabetic mice in all assayed aspects, with an induction time to start the effect of the SGs. Stevioside and steviol could increase uptake of glucose in the myocardium and brain of the diabetic mice, and decrease accumulation of glucose in the liver and kidney. The performance strength of the SGs is generally in accordance with glucosyl group numbers in their molecules.