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BACKGROUND: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. DESIGN: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). SETTING: 6 MMT clinics in China. PARTICIPANTS: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. INTERVENTION: Acupuncture or sham acupuncture 3 times a week for 8 weeks. MEASUREMENTS: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). RESULTS: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. LIMITATION: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. CONCLUSION: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.
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BACKGROUND: Jin's three needle (JTN) is a commonly utilized treatment for ischemic stroke in China. Mirror therapy (MT) is also gradually transitioning from treating limb discomfort to restoring motor function in the damaged limb. Investigations into the 2 treatments' mechanisms of action are still ongoing. We used functional magnetic resonance imaging (fMRI) technique in this study to examine the effects of JTN combined with mirror therapy MT on brain function in patients with upper limb dysfunction in ischemic stroke, as well as potential central mechanisms. The goal was to provide a solid evidence-based medical basis to support the continued use of JTN combination MT. METHODS: This study will be a single-blind, randomized, and controlled experiment. Randomization was used to assign 20 patients who met the study's eligibility requirements to the JTN + MT treatment group or the JTN control group. Each intervention will last for 4 weeks, with 6 days of treatment per week. The JTN acupuncture points are 3 temporal acupuncture points on the opposite side of the wounded limb, 3 hand acupuncture points on the injured upper limb, 3 shoulder acupuncture points, Renzhong and Baihui, The (JTN + MT) group simultaneously takes MT for 30 minutes. fMRI of the brain using BOLD and T1-weighted images was done both before and after therapy. Brain areas exhibiting changes in regional homogeneity during the pre and posttreatment periods were analyzed. RESULTS: By the end of the treatment course, Jin three-needle therapy plus MT activated more relevant brain functional regions and increased cerebral blood oxygen perfusion than Jin three-needle therapy alone (P <.05). CONCLUSION: In patients with upper limb impairment following an ischemic stroke, JTN with MT may improve brain function reconstruction in the relevant areas.
Subject(s)
Acupuncture Therapy , Ischemic Stroke , Magnetic Resonance Imaging , Upper Extremity , Humans , Upper Extremity/physiopathology , Single-Blind Method , Ischemic Stroke/physiopathology , Ischemic Stroke/therapy , Ischemic Stroke/diagnostic imaging , Acupuncture Therapy/methods , Magnetic Resonance Imaging/methods , Male , Female , Middle Aged , Brain/diagnostic imaging , Brain/physiopathology , Stroke Rehabilitation/methods , Stroke Rehabilitation/instrumentation , Aged , Adult , Needles , Treatment OutcomeABSTRACT
Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.
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Electroacupuncture (EA) stimulation has been shown to be beneficial in stroke rehabilitation; however, little is known about the neurological mechanism by which this peripheral stimulation approach treats for stroke. This study showed that both pyramidal and parvalbumin (PV) neuronal activity increased in the contralesional primary motor cortex forelimb motor area (M1FL) after ischemic stroke induced by focal unilateral occlusion in the M1FL. EA stimulation reduced pyramidal neuronal activity and increased PV neuronal activity. These results were obtained by a combination of fiber photometry recordings, in vivo and in vitro electrophysiological recordings, and immunofluorescence. Moreover, EA was found to regulate the expression/function of N-methyl-D-aspartate receptors (NMDARs) altered by stroke pathology. In summary, our findings suggest that EA could restore disturbed neuronal activity through the regulation of the activity of pyramidal and PV neurons. Furthermore, NMDARs we shown to play an important role in EA-mediated improvements in sensorimotor ability during stroke rehabilitation.
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AIMS: Electroacupuncture (EA) at the Lianquan (CV23) could alleviate swallowing dysfunction. However, current knowledge of its neural modulation focused on the brain, with little evidence from the periphery. Transient receptor potential channel vanilloid subfamily 1 (TRPV1) is an ion channel predominantly expressed in sensory neurons, and acupuncture can trigger calcium ion (Ca2+ ) wave propagation through active TRPV1 to deliver signals. The present study aimed to investigate whether TRPV1 mediated the signal of EA to the primary sensory cortex (S1) during regulation of swallowing function. METHODS: Blood perfusion was evaluated by laser speckle contrast imaging (LSCI), and neuronal activity was evaluated by fiber calcium recording and c-Fos staining. The expression of TRPV1 was detected by RNA-seq analysis, immunofluorescence, and ELISA. In addition, the swallowing function was assessed by in vivo EMG recording and water consumption test. RESULTS: EA treatment potentiated blood perfusion and neuronal activity in the S1, and this potentiation was absent after injecting lidocaine near CV23. TRPV1 near CV23 was upregulated by EA-CV23. The blood perfusion at CV23 was decreased in the TRPV1 hypofunction mice, while the blood perfusion and the neuronal activity of the S1 showed no obvious change. These findings were also present in post-stroke dysphagia (PSD) mice. CONCLUSION: The TRPV1 at CV23 after EA treatment might play a key role in mediating local blood perfusion but was not involved in transferring EA signals to the central nervous system (CNS). These findings collectively suggested that TRPV1 may be one of the important regulators involved in the mechanism of EA treatment for improving swallowing function in PSD.
Subject(s)
Acupuncture Therapy , Electroacupuncture , Stroke , Mice , Animals , Electroacupuncture/methods , Deglutition/physiology , Calcium/metabolism , Central Nervous System/metabolism , TRPV Cation Channels/metabolism , Acupuncture PointsABSTRACT
As one of the commonly used therapies for pain-related diseases in clinical practice, electroacupuncture (EA) has been proven to be effective. In chronic pain, neurons in the anterior cingulate cortex (ACC) have been reported to be hyperactive, while the mechanism by which cannabinoid type 1 receptors (CB1Rs) in the ACC are involved in EA-mediated analgesic mechanisms remains to be elucidated. In this study, we investigated the potential central mechanism of EA analgesia. A combination of techniques was used to detect the expression and function of CB1R, including quantitative real-time PCR (q-PCR), western blot (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and in vivo multichannel optical fibre recording, and neuronal activity was examined by in vivo two-photon imaging and in vivo electrophysiological recording. We found that the hyperactivity of pyramidal neurons in the ACC during chronic inflammatory pain is associated with impairment of the endocannabinoid system. EA at the Zusanli acupoint (ST36) can reduce the hyperactivity of pyramidal neurons and exert analgesic effects by increasing the endocannabinoid ligands anandamide (AEA), 2-arachidonoylglycerol (2-AG) and CB1R. More importantly, CB1R in the ACC is one of the necessary conditions for the EA-mediated analgesia effect, which may be related to the negative regulation of the N-methyl-D-aspartate receptor (NMDAR) by the activation of CB1R downregulating NR1 subunits of NMDAR (NR1) via histidine triad nucleotide-binding protein 1 (HINT1). Our study suggested that the endocannabinoid system in the ACC plays an important role in acupuncture analgesia and provides evidence for a central mechanism of EA-mediated analgesia.
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Pyramidal neuron (Pyn) hyperactivity in the anterior cingulate cortex (ACC) is involved in the modulation of pain. Previous studies indicate that the activation of α2 adrenoceptors (α2-ARs) by dexmedetomidine (DEX) is a safe and effective means of alleviating multiple types of pain. Here, we showed that systemically administered DEX can ameliorate the inflammatory pain induced by hindpaw injection of formalin (FA) and further examined the molecular and synaptic mechanisms of this DEX-elicited antinociceptive effect. We found that FA caused an increase in c-Fos expression in contralateral layer 2/3 (L2/3) ACC, and that intra-ACC infusion of DEX could also relieve phase 2 inflammatory pain behavior. DEX elicited an increase in the amplitude and frequency of miniature inhibitory post-synaptic currents (mIPSCs) and evoked IPSC amplitude, as well as a reduction in the hyperexcitability and both paired-pulse and excitation/inhibition ratios in contralateral L2/3 ACC Pyns of FA mice. These electrophysiological effects were associated with the upregulation of GABA A receptor (GABAAR) subunits. The interaction of phosphorylated Akt (p-Akt) with GABAAR subunits increased in the ACC following administration of DEX. These results suggest that DEX treatment reduces hyperactivity and enhances GABAergic inhibitory synaptic transmission in ACC Pyns, which produces analgesic effects by increasing GABAAR levels and activating the Akt signaling pathway.
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BACKGROUND AND AIMS: This paper aimed to evaluate the use of nonpharmacological interventions for the management of autism spectrum disorder (ASD). The effects of acupuncture and behavioural therapy, two nonpharmalogical interventions, on social function in ASD patients are still controversial. This meta-analysis investigated the impact of these two treatments and compared their effects. METHODS: Seven electronic databases were systematically searched to identify randomized controlled trials (RCTs) on the use of acupuncture or behavioural therapy for ASD. A meta-analysis was carried out using Review Manager 5.4 software. Continuous data are reported as mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). An assessment of methodological quality using the Cochrane risk-of-bias (ROB) tool for trials was carried out. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality (certainty) of evidence for results regarding social function indicators. RESULTS: Thirty RCTs on acupuncture and 36 on behavioural therapy were included. Compared with the control condition, body acupuncture (SMD: 0.76, 95% CI: [0.52, 1.01]; low certainty), modern acupuncture technology (SMD: 0.84, 95% CI: [0.32, 1.35]; low certainty), cognitive behavioural therapy (SMD: 0.42, 95% CI: [0.26, 0.58]; high certainty), the Denver model (SMD: 0.61, 95% CI: [0.23, 0.99]; moderate certainty) and social skills training (SMD: 0.56, 95% CI: [0.41, 0.71]; moderate certainty) improved social functioning. CONCLUSION: Behavioural therapies (such as CBT, the Denver model, social skills training), improved the social functioning of patients with ASD in the short and long term, as supported by high- and moderate-quality evidence. Acupuncture (including scalp acupuncture, body acupuncture and use of modern acupuncture technology) also improved social functioning, as supported by low- and very low-quality evidence. More high-quality evidence is needed to confirm the effect of acupoint catgut embedding and Early Intensive Behavioural Intervention (EIBI).
Subject(s)
Acupuncture Therapy , Autism Spectrum Disorder , Cognitive Behavioral Therapy , Humans , Adult , Child , Behavior Therapy , Acupuncture Points , Autism Spectrum Disorder/therapyABSTRACT
Background: Stroke is the second leading cause of death worldwide and a major cause of long-term neurological disability, imposing an enormous financial burden on families and society. This study aimed to identify the predictors in stroke patients and construct a nomogram prediction model based on these predictors. Methods: This retrospective study included 11,435 participants aged >20 years who were selected from the NHANES 2011-2018. Randomly selected subjects (n = 8531; 75%) and the remaining subjects comprised the development and validation groups, respectively. The least absolute shrinkage and selection operator (LASSO) binomial and logistic regression models were used to select the optimal predictive variables. The stroke probability was calculated using a predictor-based nomogram. Nomogram performance was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve with 1000 bootstrap resample validations. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the nomogram. Results: According to the minimum criteria of non-zero coefficients of Lasso and logistic regression screening, older age, lower education level, lower family income, hypertension, depression status, diabetes, heavy smoking, heavy drinking, trouble sleeping, congestive heart failure (CHF), coronary heart disease (CHD), angina pectoris and myocardial infarction were independently associated with a higher stroke risk. A nomogram model for stroke patient risk was established based on these predictors. The AUC (C statistic) of the nomogram was 0.843 (95% CI: 0.8186-0.8430) in the development group and 0.826 (95% CI: 0.7811, 0.8716) in the validation group. The calibration curves after 1000 bootstraps displayed a good fit between the actual and predicted probabilities in both the development and validation groups. DCA showed that the model in the development and validation groups had a net benefit when the risk thresholds were 0-0.2 and 0-0.25, respectively. Discussion: This study effectively established a nomogram including demographic characteristics, vascular risk factors, emotional factors and lifestyle behaviors to predict stroke risk. This nomogram is helpful for screening high-risk stroke individuals and could assist physicians in making better treatment decisions to reduce stroke occurrence.
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AIMS: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC). BACKGROUND: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied. OBJECTIVE: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy. METHODS: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC. RESULTS: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup. CONCLUSION: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.
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Introduction: Automatic sleep staging is a classification process with severe class imbalance and suffers from instability of scoring stage N1. Decreased accuracy in classifying stage N1 significantly impacts the staging of individuals with sleep disorders. We aim to achieve automatic sleep staging with expert-level performance in both N1 stage and overall scoring. Methods: A neural network model combines an attention-based convolutional neural network and a classifier with two branches is developed. A transitive training strategy is employed to balance universal feature learning and contextual referencing. Parameter optimization and benchmark comparisons are conducted using a large-scale dataset, followed by evaluation on seven datasets in five cohorts. Results: The proposed model achieves an accuracy of 88.16%, Cohen's kappa of 0.836, and MF1 score of 0.818 on the SHHS1 test set, also with comparable performance to human scorers in scoring stage N1. Incorporating multiple cohort data improves its performance. Notably, the model maintains high performance when applied to unseen datasets and patients with neurological or psychiatric disorders. Discussion: The proposed algorithm demonstrates strong performance and generalizablility, and its direct transferability is noteworthy among similar studies on automated sleep staging. It is publicly available, which is conducive to expanding access to sleep-related analysis, especially those associated with neurological or psychiatric disorders.
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ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia pinnata, as a natural and ethnic medicine in China, has been used for burns and wounds with a long history, which has the effect of invigorating blood and astringent sores. However, there were no reports on the advantage activity of burns. AIM OF STUDY: The purpose of this study was to screen out the best active extract part of Dalbergia pinnata and investigate its therapeutic effect on wound healing and scar resolution. MATERIALS AND METHODS: Rat burn model was established and the healing effects of extracts from Dalbergia pinnata on burn wounds were evaluated by the percentage of wound contraction and period of epithelialization. Histological observation, immunohistochemistry, immunofluorescence and ELISA were used for the examination of inflammatory factors, TGF-ß1, neovascularization and collagen fibers through the period of epithelialization. In addition, the effect of the optimal extraction site on fibroblast cells was evaluated by cell proliferation and cell migration assays. The extracts of Dalbergia pinnata were analyzed by UPLC-Q/TOF-MS or GC-MS technique. RESULTS: Compared to the model group, there were better wound healing, suppressed inflammatory factors, more neovascularization as well as newly formed collagen in the ethyl acetate extract (EAE) and petroleum ether extract (PEE) treatment groups. The ratio of Collagen I and Collagen III was lower in the EAE and PEE treatment groups, suggesting a potential for reduced scarring. Furthermore, EAE and PEE could repair wounds by up-regulating TGF-ß1 in the early stage of wound repair and down-regulating TGF-ß1 in the late stage. In vitro studies showed that both EAE and PEE were able to promote NIH/3T3 cells proliferation and migration compared with the control group. CONCLUSIONS: In this study, EAE and PEE were found to significantly accelerate wound repair and might have an inhibitory effect on the generation of scars. It was also hypothesized that the mechanism might be related to the regulation of TGF-ß1 secretion. This study provided an experimental basis for the development of topical drugs for the treatment of burns with Dalbergia pinnata.
Subject(s)
Burns , Dalbergia , Mice , Rats , Animals , Cicatrix/drug therapy , Cicatrix/pathology , Wound Healing , Transforming Growth Factor beta1/pharmacology , Collagen , Burns/drug therapyABSTRACT
Objective: To assess the clinical effectiveness of scalp acupuncture and computer assisted cognitive rehabilitation in the treatment of cognitive impairment in stroke patients. Methods: The literatures published before August 2021 in the following databases were included: PubMed, Chinese Biomedical Database, Wanfang Database, China National Knowledge Infrastructure, Database of Chinese sci-tech periodicals (VIP), EBSCO Information Services, MEDLINE and Web of Science. Only randomised controlled trials (RCTs) were included. Primary outcomes were the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and Montreal Cognitive Assessment (MoCA). Our secondary outcome was Modified Barthel Index Score (MBI). The quality of all included trials was evaluated according to the Cochrane Collaboration. This protocol was registered in PROSPERO (CRD42016048528). Results: Sixteen articles were selected including 1333 patients. The result of the meta analysis showed that the combination of scalp acupuncture and computer assisted cognitive rehabilitation had a significant improvement in the cognitive impairments. The analysis of LOTCA showed the improvement on the LOTCA (p < 0.0001, n = 410, I2 = 86%, mean difference 8.31). The meta-analysis of the MOCA showed a weighted mean difference of 3.76 and 95% confidence intervals (CI) of 2.90-4.62 (p < 0.0001, n = 301). Besides, it was showed that the combination therapy played an important role in the improvement of the score of MBI with a weighted mean difference of 9.30 and 95% confidence intervals (CI) of 5.87-12.672 (p < 0.0001, n = 278). Conclusions: Scalp acupuncture and computer assisted cognitive rehabilitation appears to be effective for stroke patients with respect to certain outcomes. However, the evidence thus far is inconclusive. Further high-quality RCTs following standardized guidelines with a low risk of bias are needed to confirm the effectiveness of acupuncture for postpartum depression.
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INTRODUCTION: Randomised controlled trials (RCTs) play an important role in evidence-based medicine. However, an article with low reporting quality may mislead both experts and the general public into an erroneous decision. Data sharing can contribute to the truthfulness and transparency of trials. Acupuncture RCTs have been increasing rapidly these years, but the reporting quality and data-sharing level of acupuncture RCTs are not clear. Thus, this study will provide the current status of the reporting quality and data-sharing level of acupuncture RCTs. METHODS AND ANALYSIS: A cross-sectional study will be conducted. The seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang Database and VIP will be searched between 1 January 2012 and 15 October 2022 to identify acupuncture RCTs. The basic characteristics of included trials will be summarised. The reporting quality for included RCTs will be assessed by the Consolidated Standards for Reporting Trials 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture. The data-sharing level will be assessed by open science practices. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This protocol has been registered in Open Science Framework Registries. The findings of this study will be submitted to a peer-reviewed academic journal.
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Acupuncture Therapy , Humans , Cross-Sectional Studies , MEDLINE , Databases, Factual , Reference Standards , Research Design , Randomized Controlled Trials as TopicABSTRACT
Background: Qihuang needle therapy is a newly developed acupuncture therapy to treat tic disorders in clinical practice. However, the mechanism to reduce tic severity remains unknown. Changes in intestinal flora and circulation metabolites are perhaps the potential pathogenesis of tic disorders. As a result, we present a protocol for a controlled clinical trial using multi-omics analysis to probe the mechanism of the Qihuang needle in managing tic disorders. Methods: This is a matched-pairs design, controlled, clinical trial for patients with tic disorders. Participants will be allocated to either an experimental group or a healthy control group. The main acupoints are Baihui (GV20), Yintang (EX-HN3), and Jueyinshu (BL14). The experimental group will receive Qihuang needle therapy for a month, while the control group will receive no interventions. Expected outcomes: The change in the severity of the tic disorder is set as the main outcome. Secondary outcomes include gastrointestinal severity index and recurrence rate, which will be calculated after a 12-week follow-up. Gut microbiota, measured by 16S rRNA gene sequencing; serum metabolomics, assessed via LC/MS; and serum zonulin, assessed by enzyme-linked immunosorbent assay (ELISA), will be used as biological specimen analysis outcomes. The present study will investigate the possible interactions between intestinal flora and serum metabolites and the improvement of clinical profiles, which may elucidate the mechanism of Qihuang needle therapy for tic disorders. Trial registration: This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200057723, Date: 2022-04-14.
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Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.
Subject(s)
Alcoholism , Ferroptosis , Melanoma , Metal-Organic Frameworks , Substance Withdrawal Syndrome , Animals , Humans , Ditiocarb/pharmacology , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/metabolism , Disulfiram/pharmacology , Disulfiram/metabolism , Melanoma/drug therapy , Copper/chemistry , Cell Line, Tumor , Amino Acid Transport System y+ABSTRACT
Background: Despite neuroinflammation being an important component of the pathology of Alzheimer's disease (AD), effective therapies to alleviate neuroinflammation are still lacking. Many animal experiments in AD have found that acupuncture may ameliorate cognition by decreasing neuroinflammation and modulating cytokines, but its effects have not been systematically examined. We aimed to assess its efficacy on neuroinflammation in AD and to investigate the potential mechanisms. Materials and methods: The following databases were searched from inception until 24 August 2022: Web of Science, EMBASE, PubMed, the Cochrane Library, and China National Knowledge Infrastructure. Animal studies that reported the efficacy of acupuncture on neuroinflammation in AD were included. The SYRCLE Robt was utilized to evaluate methodological quality. Stata 17 was utilized to conduct a meta-analysis of cytokine levels and the results of the Morris water maze. Results: 23 studies were included, with a total of 417 rats/mice. The overall quality of all included reports was medium. The results indicated that acupuncture significantly reduced the expressions of pro-inflammatory cytokines which included IL-1ß [SMD = -3.50, 95% CI (-4.31, -2.69); I 2 = 78.6%] (P < 0.05), TNF-α [SMD = -3.05, 95% CI (-3.86, -2.24); I 2 = 69.6%] (P < 0.05), IL-6 [SMD = -3.22, 95% CI (-4.62, -1.81); I 2 = 77.6%] and enhanced the expressions of anti-inflammatory cytokines including IL-4 [SMD = 2.77, 95% CI (1.95, 3.59); I 2 = 33.9%] (P < 0.05), IL-10 [SMD = 1.84, 95% CI (1.20, 2.49); I 2 = 41.0%] (P < 0.05) in an animal model of AD. Regarding the Morris water maze, compared to the control group, the acupuncture group showed a shorter escape latency [SMD = -2.23, 95% CI (-2.89, -1.57); I 2 = 79.2%] (P < 0.05), longer duration in platform quadrant [SMD = 2.34, 95% CI (1.44, 3.23); I 2 = 81.7%] (P < 0.05), and increased platform crossing number [SMD = 2.79, 95% CI (2.06, 3.53); I 2 = 71.9%] (P < 0.05). Conclusion: Acupuncture may reduce neuroinflammation in AD by modulating cytokine expression. This modulation significantly improved cognitive function in animal models of AD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354878.
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Background: Previous research has found that transcutaneous auricular vagus nerve stimulation (taVNS) can improve working memory (WM) performance. It has also been shown that 0.1 Hz slow-paced breathing (SPB, i.e., breathing at a rate of approximately 6 breaths/min) can significantly influence physical state and cognitive function via changes in autonomic afferent activity. In the present study, we investigated the synergistic effects of taVNS and SPB on WM performance. Methods: A total of 96 healthy people participated in this within-subjects experiment involving four conditions, namely taVNS, SPB, combined taVNS with SPB (taVNS + SPB), and sham. Each participant underwent each intervention for 30 min and WM was compared pre- and post-intervention using the spatial and digit n-back tasks in a random order four times. Permutation-based analysis of variance was used to assess the interaction between time and intervention. Results: For the spatial 3-back task, a significant interaction between time and intervention was found for the accuracy rate of matching trials (mACC, p = 0.03). Post hoc analysis suggested that both taVNS and taVNS + SPB improved WM performance, however, no significant difference was found in the SPB or sham groups. Conclusion: This study has replicated the effects of taVNS on WM performance reported in previous studies. However, the synergistic effects of combined taVNS and SPB warrant further research.