Predicting acupuncture efficacy for major depressive disorder using baseline clinical variables: A machine learning study.

Acupuncture is a viable treatment option for major depressive disorder (MDD). However, its effectiveness varies among patients. This study aimed to develop a model to predict the efficacy of acupuncture therapy for MDD using machine learning and baseline clinical variables. A total of 124 patients with MDD from five research centers were included in our machine learning study. All patients underwent acupuncture treatment for 6 weeks and the efficacy of the treatment was evaluated using the Hamilton Depression Scale-17 (HAMD-17). The max-relevance and min-redundancy (mRMR) algorithm and Pearson correlation analysis were used for selecting 11 significant features from 26 baseline clinical variables for model training. We compared the performance of five machine learning models, including logistic regression, support vector machine, K-nearest neighbor, random forest, and XgBoost, in predicting the effect of acupuncture in relieving major depression. Among the five models, XgBoost performed the best with an area under the receiver operating characteristic curve (AUC) of 0.835, an accuracy of 0.730, a sensitivity of 0.670, a specificity of 0.774, and an F1 score of 0.751. The key predictive variables identified were anxiety score in the self-rating depression scale (SDS), the traditional Chinese medicine syndrome of deficiency in both heart and spleen, and body mass index (BMI). The study demonstrates that the developed model can help physicians predict the patients who will benefit from acupuncture treatment, which is of positive significance for improving the clinical efficacy of acupuncture on MDD.

Electroacupuncture alleviated depression-like behaviors in ventromedial prefrontal cortex of chronic unpredictable mild stress-induced rats: Increasing synaptic transmission and phosphorylating dopamine transporter.

AIMS: Electroacupuncture (EA) shows advantages in both clinical practice and depression animal models. Dopaminergic-related dysfunction in the prefrontal cortex (PFC) may be a hidden antidepressant mechanism of EA, where dopamine transporter (DAT) plays an essential role. This study aimed to investigate the synaptic transmission and DAT-related changes of EA in depression. METHODS: Male Sprague-Dawley rats were subjected to 3-week chronic unpredictable mild stress (CUMS). The successfully modeled rats were then randomly and equally assigned to CUMS, selective serotonin reuptake inhibitor (SSRI), and EA or SSRI + EA groups, followed by a 2-week treatment respectively. After monitoring body weight and behavioral tests of all rats, the ventromedial PFC (vmPFC) tissue was collected for electrophysiology and the expression detection of DAT, phosphorylated DAT (p-DAT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and trace amine-associated receptor 1 (TAAR1). RESULTS: Depressive-like behaviors induced by CUMS were alleviated by EA, SSRI, and SSRI + EA treatments through behavioral tests. Compared with CUMS group, EA improved synaptic transmission in vmPFC by upregulating spontaneous excitatory postsynaptic currents amplitude. Molecularly, EA reversed the increased total DAT and p-DAT expression as well as the decreased ratio of p-DAT/total DAT along with the activation of TAAR1, cAMP, and PKA in vmPFC. CONCLUSION: We speculated that the antidepressant effect of EA was associated with enhanced synaptic transmission in vmPFC, and the upregulated phosphorylation of DAT relevant to TAAR1, cAMP, and PKA may be the potential mechanism.

Electroacupuncture Improves Depression-Like Behavior by Regulating the Abundance of Lactobacillus and Staphylococci in Mice.

BACKGROUND: Growing evidence suggests that gut microbiota can affect depression-like behavior, and electroacupuncture (EA) can regulate the composition and abundance of gut microbiota. At the same time, not a lot of research has been done on how EA affects gut microbiota to depression-like behavior. The objective of this study was to study the associated mechanisms by which EA exerts antidepressant effects by modulating gut microbiota. METHODS: Twenty-four C57BL/6 male mice were randomly divided into three groups, one group (n = 8) was the normal control group (NC). And the other two groups was chronic unpredictable mild stress for modeling + electroacupuncture group (CUMS + EA) (n = 8) and chronic unpredictable mild stress for modeling group (CUMS) (n = 8). Both CUMS and EA groups were subjected to 28 days of CUMS, but only the EA group received an additional 14 days of EA procedure. Behavior tests were used to determine the antidepressant effect of EA. Sequencing of the 16S ribosomal RNA (rRNA) gene was applied to examine alterations in the intestinal microbiome between groups. RESULTS: The findings were compared to those of the NC group, the sucrose preference rate and the total distance of Open Field Test (OFT) in CUMS group decreased, the abundance of Lactobacillus decreased, while the abundance of staphylococci increased. After the intervention of EA, the sucrose preference index and the total distance of OFT increased, the abundance of Lactobacillus increased, while the abundance of staphylococci decreased. CONCLUSIONS: These findings indicated EA may play an antidepressant effect by adjusting the abundance of Lactobacillus and staphylococci.

Efficacy of electroacupuncture in assisting postoperative healing of distal radius fractures: study protocol for a randomized controlled trial.

BACKGROUND: Manual reduction and surgical treatment are common methods for distal radius fractures (DRFs). The existing literature suggests that postoperative combined rehabilitation treatment and medication are effective for the healing of DRFs. However, the side effects of these treatments remain to be solved. Previous studies have shown that electroacupuncture (EA) can effectively relieve wrist swelling and improve the joint function in patients with DRFs, but more evidence is needed to prove the effectiveness of EA. This trial aims to explore the efficiency and feasibility of combined EA treatment in postoperative treatment of DRFs compared with routine treatment. METHODS: This is a parallel randomized controlled trial. A total of 222 patients diagnosed with moderate DRFs will be recruited and randomly assigned to an EA group or a routine treatment group at a ratio of 1:1. Routine treatment group will receive medication and rehabilitation. Yangxi (LI 5), Yangchi (TE 4), Yanggu (SI 5), Hegu (LI 4), and Taiyuan (LU 9) will be selected in the EA group for intervention three times a week on the basis of routine treatment. Both groups will receive 8 weeks of treatment and 4 weeks of follow-up. The primary outcome will be ulnar positive variance. The secondary outcomes will include radiographic healing rate, bone strength, hemorheological indices, serum biochemical indicators and inflammatory factors, grip strength, wrist swelling score, patient-rated wrist evaluation, disabilities of arm, shoulder and hand, and visual analogue scale. Outcomes will be evaluated at baseline, postoperative 3rd day, 2nd, 4th, 6th, 8th, and 12th weeks. DISCUSSION: The results of this study will help establish a more optimized scheme to treat patients with DRFs. Trial registration Chinese Clinical Trial Registry ChiCTR2200062857. Registered on 21 August 2022, www.chictr.org.cn/com/25/showproj.aspx?proj=175567 .

Electroacupuncture as a rapid-onset and safer complementary therapy for depression: A systematic review and meta-analysis.

Background: Electroacupuncture (EA) is a promising therapy for depression. However, a comprehensive review of EA for depression is needed. Methods: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) guidelines to evaluate the efficacy and safety of EA for depression. Potentially relevant trials and reviews were searched in MEDLINE, EMBASE, PsycINFO, and CENTRAL from inception to March 2022. EA alone and combined with other therapy were eligible for inclusion. The severity of depression during and after treatment and the number of adverse events were assessed as outcomes. Risk of bias (ROB) evaluation, subgroup analysis, sensitivity analysis, reporting bias assessment, and GRADE system evaluation were also conducted. Results: Thirty-four trials were included. The overall ROB was medium. Low-quality evidence showed that the efficacy of EA was not less than that of antidepressants [EA + selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)] and manual acupuncture (MA). EA and EA + SSRIs had better efficacy than SSRIs alone in decreasing the severity of depression during the early treatment. Moderate-quality evidence also showed that EA and EA + SSRIs were safer than SSRIs alone. Sensitivity analysis was mostly not feasible. Major publication bias was unlikely. Conclusion: These results indicate that the efficacy of EA is not less than that of antidepressants and MA. Moreover, EA and EA + SSRI treatments show a more rapid onset and greater safety than SSRIs. More high-quality trials are needed for further confirmation. Systematic review registration: [www.crd.york.ac.uk/prospero/display_ record.php?RecordID=329143], identifier [CRD42022329143].

Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ-based proteomics analysis in a rat model of CUMS.

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-l-amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings suggested that the dopaminergic signaling pathway in PFC may be involved in the antidepressant mechanisms of EA.

Electroacupuncture alleviated the depression-like behavior by regulating FGF2 and astrocytes in the hippocampus of rats with chronic unpredictable mild stress.

Studies have shown that basic fibroblast growth factor (FGF2) is a neurotrophic factor associated with depression. Electroacupuncture (EA) has been shown to be an effective treatment for depression. In the current study, we observed the effects of EA on hippocampal FGF2 and astrocytes, and further investigated the mechanism underlying antidepressant effect of EA. The chronic unpredictable mild stress (CUMS) method were selected to induce depressive-like behaviors of rats. Paroxetine is a commonly used antidepressant and was used as a positive control drug in this experiment. The male adult Sprague Dawley (SD) rats were randomized to four experimental groups (normal control group, CUMS group, EA group and paroxetine group, n = 10/group). EA intervention was administered once daily for 14 days at acupuncture points Baihui (GV20) and Yintang (GV29). Rats in the paroxetine group received daily paroxetine administered intragastrical. Behavioral test, immunohistochemistry (IHC), western blot (WB) and quantitative real-time PCR (qPCR) were conducted to evaluate the intervene effect and the changes of FGF2 and astrocyte marker (glial fibrillary acidic protein, GFAP). The results showed that EA and paroxetine could improve depression-like behavior in CUMS rats, and up-regulated the expression level of FGF2 in the hippocampus, increased GFAP protein expression and the mean optical density of GFAP-immunoreactive astrocyte (GFAP-ir astrocyte). Our findings have identified that EA could ameliorate depressive-like behaviors possibly by regulating the expression of FGF2 in the hippocampus, and the mechanism might be related to the effect of FGF2 on astrocytes.

The Effectiveness of Tai Chi in Patients With Breast Cancer: An Overview of Systematic Reviews and Meta-Analyses.

BACKGROUND: As a mind-body exercise, Tai Chi (TC) may have a positive impact on physical function and psychological well-being in patients with breast cancer (BC). The aim of this current overview of systematic reviews (SRs) and meta-analyses (MAs) was to identify and summarize the existing evidence regarding the effectiveness of TC in patients with BC. METHODS: A computerized search of electronic databases was performed to identify relevant SRs/MAs of TC related to BC from inception to June 2020. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklists were used to assess the methodological quality and reporting quality of SRs and MAs, respectively. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the evidence quality of outcome measures. RESULTS: Six SRs/MAs in which quantitative synthesis was used to assess various outcomes of TC related to BC were included in this overview. The quality of the SRs/MAs and the evidence quality of the outcome measures were generally unsatisfactory. The limitations of the past SRs/MAs were the lack of a protocol and registration, a list of excluded studies, or inadequately reported computational details of meta-analyses. The critical problems were that the qualitative data synthesis relied on the trials with small sample sizes and of critical low quality. CONCLUSIONS: TC is possibly beneficial to BC treatment. However, further rigorous and comprehensive studies are required to provide robust evidence for definitive conclusions.

Acupuncture at LR3 and KI3 shows a control effect on essential hypertension and targeted action on cerebral regions related to blood pressure regulation: a resting state functional magnetic resonance imaging study.

OBJECTIVE: The aim of this study was to investigate the effects of acupuncture at LR3 and KI3 on hypertension at different time points and on related cerebral regions using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: We randomly divided 29 subjects into two groups: Group A (receiving acupuncture at LR3 + KI3; 15 subjects) and group B (receiving acupuncture at LR3 and a sham location not corresponding to any traditional acupuncture point; 14 subjects). Acupuncture was performed. Blood pressure (BP) changes were recorded and analyzed using SPSS 20.0 statistical software. We used a 3.0T MRI scanner and standard GE 8 channel head coil to collect whole brain fMRI data in both groups. Data analysis and processing was based on the R2009a MATLAB platform. REST 1.8 software was used to analyze the whole brain amplitude of low-frequency fluctuation (ALFF). RESULTS: After acupuncture, a statistically significant reduction in BP at different time points was observed in group A. In group B, a statistically significant reduction was found only in diastolic blood pressure (DBP) and was not sustained. Acupuncture at LR3 + KI3 specifically affected brain areas involved in BP regulation, as well as those involved in auditory sense, speech, vision, movement and sensation. CONCLUSION: Acupuncture at LR3 + KI3 showed positive immediate and long-term effects on BP, particularly systolic blood pressure (SBP). After ALFF analysis, we concluded that LR3 + KI3 activates brain areas related to BP regulation. In addition, after acupuncture at LR3 + KI3, a highly targeted effect was observed in brain areas associated with BP. In addition, extracerebral areas involving vision, motion control, cognition and hearing were activated, which could potentially contribute to the mitigation of hypertensive complications in patients in an advanced stage of the disease.

Smart Responsive Nanoformulation for Targeted Delivery of Active Compounds From Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) has been used to treat disorders in China for ~1,000 years. Growing evidence has shown that the active ingredients from TCM have antibacterial, antiproliferative, antioxidant, and apoptosis-inducing features. However, poor solubility and low bioavailability limit clinical application of active compounds from TCM. "Nanoformulations" (NFs) are novel and advanced drug-delivery systems. They show promise for improving the solubility and bioavailability of drugs. In particular, "smart responsive NFs" can respond to the special external and internal stimuli in targeted sites to release loaded drugs, which enables them to control the release of drug within target tissues. Recent studies have demonstrated that smart responsive NFs can achieve targeted release of active compounds from TCM at disease sites to increase their concentrations in diseased tissues and reduce the number of adverse effects. Here, we review "internal stimulus-responsive NFs" (based on pH and redox status) and "external stimulus-responsive NFs" (based on light and magnetic fields) and focus on their application for active compounds from TCM against tumors and infectious diseases, to further boost the development of TCM in modern medicine.

EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus.

Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both p < 0.05), but these two therapies had nonsignificant difference between each other (p > 0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p < 0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.

Effectiveness of Acupuncture in the Treatment of Parkinson's Disease: An Overview of Systematic Reviews.

Background: The effects of acupuncture on Parkinson's disease (PD) outcomes remain unclear. The aim of this overview was to comprehensively evaluate the methodological quality and applicability of the results of systematic reviews (SRs)/meta-analyses (MAs) that examined the use of acupuncture to treat PD. Methods: Eight databases were searched to retrieve SRs/MAs on the use of acupuncture for the treatment of PD. Two reviewers independently screened and extracted the data using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) checklist to evaluate the methodological quality and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria to assess the evidence quality of the included reviews. Results: A total of 11 SRs/MAs were included. According to the AMSTAR-2 checklist results, all included SRs/MAs were rated as very-low-quality studies. The GRADE criteria revealed 20 studies with very-low-quality evidence, 9 with low-quality evidence, 3 with moderate-quality evidence, and 0 with high-quality evidence. Descriptive analysis showed that acupuncture appears to be a clinically effective and safe treatment for PD. Conclusions: The use of acupuncture for the treatment of PD may be clinically effective and safe. This conclusion must be interpreted cautiously due to the generally low methodological quality and low quality of evidence of the included studies.

Different Brain Activation after Acupuncture at Combined Acupoints and Single Acupoint in Hypertension Patients: An Rs-fMRI Study Based on ReHo Analysis.

BACKGROUND: Acupuncture is proved to be effective on hypertension by numerous studies and resting-state functional magnetic resonance imaging (Rs-fMRI) is a widely used technique to study its mechanism. Along with lower blood pressure, patients with hypertension receiving acupuncture also presented improvement in function of cognition, emotion, language, sematic sensation, and so on. This study was a primary study to explore the acting path of acupuncture at combined acupoints in stimulated brain areas related to such functions. METHODS: In this research, regional homogeneity (ReHo) was applied to analyze the Rs-fMRI image data of brain activities after acupuncture at LR3, KI3, and LR3+KI3 and to compare the differences of functional brain activities between stimulating combined acupoints and single acupoint under pathological conditions. A total of thirty hypertension patients underwent Rs-fMRI scanning before acupuncture treatment and then were randomly divided into three groups following random number table, the LR3 group (3 males and 7 females), the KI3 group (3 males and 7 females), and the LR3+ KI3 group (4 males and 6 females) for needling, respectively. When the 30-min treatment finished, they received a further Rs-fMRI scanning. The Rs-fMRI data before and after the acupuncture treatment were analyzed through ReHo. RESULTS: Compared with preacupuncture, respectively, ReHo values increased in Brodmann areas (BAs) 3, 18, and 40 and decreased in BAs 7 and 31 in LR3+ KI3 group. However, ReHo values only decreased in BA7 of KI3 group while the results showed no significant difference of brain regions in LR3 group between pre- and postacupuncture. Compared with LR3 group, LR3+KI3 group exhibited decreased ReHo values in BAs 7, 9, and 31. Meanwhile, compared with KI3 group, LR3+KI3 group exhibited increased ReHo values in the BAs 2, 18, 30, and 40 and decreased ReHo values in BA13. CONCLUSION: Combined acupoints of LR3 and KI3 could act on wider brain areas than the sum of single acupoints, whose functions include emotional processing, cognition, somatic sensation, spatial orientation, language production, and vision.

Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer's disease: a positron emission tomography study.

The acute effect of acupuncture on Alzheimer's disease, i.e., on brain activation during treatment, has been reported. However, the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear. Therefore, in this study, we performed long-term needling at Zusanli (ST36) or a sham point (1.5 mm lateral to ST36) in a rat Alzheimer's disease model, for 30 minutes, once per day, for 30 days. The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning. Positron emission tomography images were processed with SPM2. The brain areas activated after needling at ST36 included the left hippocampus, the left orbital cortex, the left infralimbic cortex, the left olfactory cortex, the left cerebellum and the left pons. In the sham-point group, the activated regions were similar to those in the ST36 group. However, the ST36 group showed greater activation in the cerebellum and pons than the sham-point group. These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease.