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Cardio-cerebrovascular disease (CCVD) has become the leading cause of human mortality with the coming acceleration of global population aging. Atherosclerosis is among the most common pathological changes in CCVDs. It is also a multifactorial disorder; oxidative stress caused by excessive production of reactive oxygen species (ROS) has become an important mechanism of atherosclerosis. Chinese herbal medicine (CHM) is a major type of natural medicine that has made great contributions to human health. CHMs are increasingly used in the auxiliary clinical treatment of atherosclerosis. Although their mechanism of action is unclear, CHMs can exert a variety of antiatherosclerosis effects by regulating intracellular ROS. In this review, we discussed the mechanism of ROS regulation in atherosclerosis and analyzed the role of CHMs in the treatment of atherosclerosis via ROS.

Objectives When citrate and pyruvate were utilized to strengthen ATP generation for high cAMP production, oxidative stress became more severe in cells resulting in lower cell viability and cAMP formation at the late fermentation phase. To further improve cAMP biosynthesis, the effects of polyphosphate on cAMP fermentation performance together with intracellular ATP and oxidation levels were investigated under high oxidative stress condition and then high efficient cAMP fermentation process based on polyphosphate and salvage synthesis was developed and studied. Results With 2 g/L-broth sodium hexametaphosphate added at 24 h was determined as the optimal condition for cAMP production by Arthrobacter sp. CCTCC 2013431 in shake flasks. Under high oxidative stress condition caused by adding 15 mg/L-broth menadione, cAMP contents and cell viability were improved greatly due to hexametaphosphate addition and also exceeded those of control (without hexametaphosphate and menadione added) when fermentations were conducted in a 7 L bioreactor. Meanwhile, ATP levels and antioxidant capacity were improved obviously by hexametaphosphate as well. Moreover, a fermentation process with hexametaphosphate and hypoxanthine coupling added was developed by which cAMP concentration reached 7.25 g/L with an increment of 87.1% when compared with only hypoxanthine added batch and the high ROS contents generated from salvage synthesis were reduced significantly. Conclusion Polyphosphate could improve intracellular ATP levels and antioxidant capacity significantly under high oxidative stress condition resulting in enhanced cell viability and cAMP fermentation production no matter by de novo synthesis or salvage synthesis.

Meige syndrome is a neurological disorder discovered by Henry Meige a French neurologist. The initial clinical manifestations are blepharospasm in both eyes and the characteristic facial appearance of tiger face lines. The patient displays an abnormal facial expression. Trauma, psychological, endocrine, and pharmacological factors may play a role in secondary Meige syndrome. Here we describe these clinical signs with pictures.

BACKGROUND: Ischemic stroke is a common type of stroke associated with reorganization of functional network of the brain. OBJECTIVE: This pilot study aimed to investigate the characteristics of functional brain networks based on EEG in patients with acute ischemic stroke. METHODS: Seven patients with ischemic stroke within 72 hours of onset and seven healthy controls were enrolled in the study. Dynamic EEG monitoring and clinical information were repeatedly collected within 72 hours (T1), on the 5th day (T2), and on the 7th day (T3) of stroke onset. A directed transfer function was employed to construct functional brain connection patterns. Graph theoretical analysis was performed to evaluate the characteristics of functional brain networks. RESULTS: First, we found that the brain networks of ischemic stroke patients were quite different from the healthy controls. The clustering coefficient (0.001

Objectives In our previous study, citrate was used as auxiliary energy substance for improving cAMP fermentation performance, however, the regulation mechanism of citrate on improved cAMP contents was not clear. To elucidate the regulation mechanism, cAMP fermentations with/without citrate addition were conducted in a 7 L fermentor using Arthrobacter sp. CCTCC 2013431 and assays on key enzymes activities, energy metabolism level, amino acids contents and peroxidation level were performed. Results With 3 g/L-broth sodium citrate added, cAMP concentration and conversion yield from glucose reached 4.34 g/L and 0.076 g/g which were improved by 30.7% and 29.8%, respectively, when compared with those of control. Citrate changed carbon flux distribution among different routes and more carbon flux was directed into pentose phosphate pathway beneficial to cAMP synthesis. Meanwhile, energy metabolism together with precursor amino acids levels were improved significantly owing to strengthened metabolic intensity of tricarboxylate cycle by exogenous citrate utilization which provided energy and substance basis for cAMP production. Moreover, higher glutamate synthesis and oxidative stress caused by citrate addition consumed excessive NADPH derived from pentose phosphate pathway by which feedback suppression for pentose phosphate pathway was relieved efficiently.Conclusion Citrate promoted cAMP fermentation production by Arthrobacter sp. CCTCC2013431 due to enhanced precursor amino acids, energy metabolism level and relieved feedback suppression for pentose phosphate pathway.

Background: Pulmonary infection is the most common complication to develop after intracerebral hemorrhage (ICH). Antibiotics have certain limitations when used to treat pulmonary infection, while Tanreqing injection (TRQI) is extensively used to treat pulmonary infection as an adjuvant to antibiotics. The aim of this meta-analysis was to investigate the clinical efficacy of TRQI for the treatment of lung infection secondary to ICH. Methods: Randomized controlled trials (RCTs) assessing the combination of TRQI and antibiotics compared to antibiotics alone for pulmonary infection after ICH were comprehensively searched for in 7 electronic databases from their establishment to August 2020. Two independent researchers conducted the literature retrieval, screening, and data extraction. The assessment tool of Cochrane risk of bias and Review Manager 5.3 software were applied to assess the methodological quality and analyze the data, respectively. Results: Seventeen RCTs involving 1122 patients with pulmonary infection after ICH were included. Compared to antibiotics alone, the combination treatment enhanced the clinical effective rate, shortened the hospital stay, reduced the white blood cell, procalcitonin, and C-reactive protein levels, ameliorated the times to the resolution of fever, cough, and lung rales, and increased the oxygenation index. The evidence indicated that TRQI combined with antibiotics caused no adverse reactions. Conclusions: Our study showed that the combination of TRQI and antibiotics was effective for treating pulmonary infection after ICH. However, high-quality multicenter RCTs are needed to further verify the clinical efficacy of TRQI due to the publication bias and the low methodological quality of the included RCTs.

Background. Poststroke aphasia (PSA) is a disabling condition that decreases the quality of life, and the duration of the disease harms the quality of life of PSA patients. Acupuncture has been widely employed for PSA. There is some evidence for the immediate treatment efficacy of acupuncture for PSA; however, long-term results after acupuncture may be poorer. Methods. This is a multicentre, randomized, blinded, nonacupoint (NA) acupuncture controlled, multimodal neuroimaging clinical trial. A total of 48 subjects with subacute PSA will be randomly assigned to an acupoint group or an NA control group. The acupoint group will receive acupuncture with normal needling at DU20, EX-HN1, HT5, GB39, EX-HN12, EX-HN13, and CV23. The NA control group will receive acupuncture in locations not corresponding to acupuncture points as sham acupoints. Both groups will receive identical speech and language therapy thrice a week for four weeks. The primary outcome will be the change in the aphasia quotient (AQ) score measured by the Western Aphasia Battery (WAB) test during the 12th week after randomization. Participants will be blindly assessed at prerandomization (baseline) and 4 weeks, 12 weeks, and 24 weeks after randomization. The secondary outcomes include the Boston Diagnostic Aphasia Examination (BDAE) score, the Disease Prognosis Scale score for ischaemic stroke, etc. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) will also be performed at 4-time intervals as secondary outcomes. All scores and image evaluations will be taken at the same point as the linguistic evaluation. The multilevel evaluation technique will be used to assess the long-term efficacy of acupuncture therapy. MRI scans and EEG will be used to assess acupuncture-related neuroplasticity changes. Discussion. The results from our trial will help to supply evidence for the long-term acupuncture effects for PSA over a long follow-up period. It will provide valuable information for future studies in the field of PSA treatment. The trial was registered at the Chinese Clinical Trial Registry on 16 March 2020 (ChiCTR2000030879).

To investigate whether virtual reality (VR) interventions have beneficial effects on the functional communication and language function of patients with post-stroke aphasia (PSA). We searched nine electronic literature databases and two clinical registry platforms to identify randomized controlled trials (RCTs) and quasi-RCTs performed up to September 2020. Screening, quality assessment, and data collection were performed by two authors independently, using standard protocols. Data aggregation and risk of bias evaluation were conducted using Review Manager Version 5.4. The quality of evidence was evaluated with GRADEpro. A total of five studies involving 121 participants met the inclusion criteria and were appraised. Four studies were included in the quantitative synthesis. VR reduced the severity of language impairment with borderline significance [SMD (95%CI) = 0.70[0.01, 1.39], P=0.05]. The meta-analysis showed no statistical difference in functional communication [SMD (95%CI) =0.41[−0.29, 1.12], P=0.25], word finding [SMD (95%CI) =0.42[−0.24, 1.08], P=0.21], and repetition [SMD (95%CI) =0.16[−0.62, 0.94], P=0.68] between VR group and the control group. This review demonstrated a borderline positive clinical effect of VR for the severity of language impairment when compared with conventional rehabilitation therapy. Conversely, VR had no effect on functional communication, word finding, and repetition. Further research is warranted to reach more definite conclusions.

Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123I]-VEGF scintigraphy in patients with histologically verified brain tumors. 23 consecutive patients (9 women and 14 men aged 30–83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study. All patients had undergone [123I]-VEGF scintigraphy. SPECT examinations of brain were performed 30 min and 18 h after injection. Additional [11C]-methionine PET ([11C]-MET PET) was performed in eight of the 23 patients. Both [123I]-VEGF and [11C]-MET PET were evaluated visually and semiquantitatively by tumor-to-normal brain uptake ratio (T/N ratio). Thresholds of the T/N ratio were evaluated by analysis of receiver operating characteristics (ROC). Overall survival (OS) was estimated using the Kaplan-Meier method. World Health Organization (WHO) grade IV glioma lesions showed [123I]-VEGF uptake 18 h after the injection, whereas other brain tumors of grade II or III showed negative results. There was no significant difference in the tumor size between VEGF positive and VEGF negative tumors. Patients with [123I]-VEGF T/N ratio threshold

The present study aims to investigate the correlation between EEG features and short-term prognosis in patients who have experienced an acute ischemic stroke.The present study included 29 patients who had experienced an acute ischemic stroke and were treated at the Beijing Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine between January 2010 and January 2012. Patients were evaluated using the revised Brain Symmetry Index (r-BSI), National Institutes of Health Stroke Scale, and Glasgow Coma Scale. Functional outcomes were assessed 21 days after admission using the Barthel Index and modified Rankin Scale. Two groups were created based on the Barthel Index (60 vs. ≥60) and modified Rankin Scale (3 vs. ≥3).Significant differences were observed in r-BSI, National Institutes of Health Stroke Scale, and Glasgow Coma Scale scores between the two groups. Poor functional outcomes were associated with higher r-BSI and National Institutes of Health Stroke Scale scores as well as lower Glasgow Coma Scale scores in comparison with those obtained for patients with good prognosis. Logistic regression analysis revealed that r-BSI scores at admission exhibited significant negative correlation with Barthel Index scores (-2.070, P = 0.049) and significant positive correlation with modified Rankin Scale scores (2.256, P = 0.033).The r-BSI may be a valuable prognostic tool in the prediction of short-term outcomes for patients who have experienced acute ischemic stroke.The early prediction of functional outcomes after stroke may enhance clinical management and minimize short-term mortality.

Ethnopharmacological relevance Xuesaitong (XST) is a traditional Chinese medicine injection with neuroprotective properties and has been extensively used to treat stroke for many years. The main component of XST is Panax notoginseng saponins (PNS), which is the main extract of the Chinese herbal medicine Panax notoginseng. Aim of the study In this study, we investigated whether XST provided long-term neuroprotection by inhibiting neurite outgrowth inhibitor-A (Nogo-A) and the ROCKII pathway in experimental rats after middle cerebral artery occlusion (MCAO) and in SH-SY5Y cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R). Materials and methods Rats with permanent MCAO were administered XST, Y27632, XST plus Y27632, and nimodipine for 14 and 28 days. Successful MCAO onset was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological deficit score (NDS) was used to assess neurological impairment. Hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) were performed to evaluate cerebral ischemic injury and the neuroprotective capability of XST. Nogo-A levels and the ROCKII pathway were detected by IHC analysis, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) to explore the protective mechanism of XST. OGD/R model was established in SH-SY5Y cells. Cell counting kit 8 (CCK8) was applied to detect the optimum OGD time and XST concentration. The expression levels Nogo-A and ROCKII pathway were determined using western blotting. Results Our results showed that XST reduced neurological dysfunction and pathological damage, promoted weight gain and synaptic regeneration, reduced Nogo-A mRNA and protein levels, and inhibited the ROCKII pathway in MCAO rats. CCK8 assay displayed that the optimal OGD time and optimal XST concentration were 7 h and 20 μg/mL respectively in SH-SY5Y cells. XST could evidently inhibit OGD/R-induced Nogo-A protein expression and ROCKII pathway activation in SH-SY5Y cells. Conclusions The present study suggested that XST exerted long-term neuroprotective effects that assisted in stroke recovery, possibly through inhibition of the ROCKII pathway.

Highlights • The left UF damage is associated with PSSA language impairment severity. • The left UF FA is decreased and correlated with language impairment in PSSA. • The left temporal pole ALFF is associated with PSSA language impairment and recovery. • Our results support the disconnection theory in PSSA pathology and recovery., Aphasia, one of the most common cognitive impairments after stroke, is commonly considered to be a cortical deficit. However, many studies have reported cases of post subcortical stroke aphasia (PSSA). The pathology and recovery mechanism of PSSA remain unclear. This study aimed to investigate PSSA mechanism through a multimodal magnetic resonance imaging (MRI) approach and a two-session study design (baseline and one month after treatment). Thirty-six PSSA patients and twenty-four matched healthy controls (HC) were included. All patients had subcortical infarctions involving left subcortical white matter for 1 to 6 months. The patients underwent MRI scan and Western Aphasia Battery (WAB) examination before and after one month’s comprehensive treatment. Region-wise lesion-symptom mapping (RLSM), tractography, fractional anisotropy (FA), and amplitude of low-frequency fluctuations (ALFF) analysis were conducted. After MRI preprocessing and exclusion, FA analysis included 35 patients pre-treatment and 16 patients post-treatment. ALFF analysis included 30 patients pre-treatment and 14 patients post-treatment. We found: 1) the amount of damage in the left uncinate fasciculus (UF) was associated with WAB aphasia quotient (AQ); 2) the left UF FA and left temporal pole (TP) ALFF were decreased and positively correlated with WAB-AQ, spontaneous speech, and naming in PSSA patients; and 3) PSSA patients showed increased left TP ALFF when their language ability recovered after treatment. The left TP ALFF change was positively correlated with AQ change. Our results demonstrate the importance of left UF and left TP (one of the cortical terminals of the left UF) in PSSA pathology and recovery. These results may further provide support for the disconnection theory in the mechanism of PSSA.

Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort. Network communication efficiency was quantified, along with the network's betweenness centrality (Bc), global efficiency, local efficiency, and shortest path length. Regarding cognition, TT carriers had significant negative correlations between age and memory performance and between age and executive functions. A network analysis showed that TT carriers had an accelerated age-related loss of Bc and that regional Bc decreased in the left inferior frontal gyrus pars opercularis, the left posterior cingulate cortex, the right inferior occipital gyrus (IOG.R), and the left angular gyrus (ANG.L). Additional brain-behavior relationship analyses showed that polymorphism of rs405509 and age have strong interaction effects on the association of nodal Bc and cognition, mainly in the IOG.R and ANG.L. These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.

In this study we investigated the neurolinguistic and neuroimaging characteristics of post-stroke motor aphasia patients. The effects of acupuncture on cortex activation by using magnetic resonance imaging (MRI) in patients with motor aphasia were also studied. In this study 43 patients with motor aphasia after stroke were assessed according to Clinical Rehabilitation Research Center aphasia examination (CRRCAE) for linguistic evaluation and MRI and computed tomography (CT) were used for the analyses of brain lesions. The MRI imaging data were also examined using statistical parametric mapping (SPM8) software. Cortex activation images during acupuncture were analyzed using generalized linear model analysis. The results of MRI and CT showed diverse brain lesion regions of post-stroke motor aphasia including the cortex, subcortex and cortex together with the subcortex. The language-related brain areas are activated by acupuncture including frontal, temporal, parietal and occipital lobes as well as insula, precuneus and other wide range of brain function areas as shown by MRI. Our study showed that the brain lesion regions in post-stroke motor aphasia were not completely consistent with the classical motor speech center. By using MRI our study results suggest that the formation of cognitive language may be involved with the cortical-subcortical functional networks. Acupuncture may be useful for treatment of motor aphasia after stroke.

In this meta-analysis the authors evaluated the effectiveness of acupuncture in improving functional communication and language function in post-stroke aphasia (PSA) patients. Data sources: MEDLINE, EMBASE, CENTRAL, AMED, SinoMed, CNKI, VIP, and Wanfang databases, ICTRP, ISRCTN, EUCTR, ClinicalTrials.gov, and Stroke Trials Registries. A search was carried out for randomized controlled trials (RCTs) investigating the effects of acupuncture compared with no treatment or placebo acupuncture on post-stroke aphasia (PSA). The searched records were independently screened by two authors, who extracted the data, and assessed risk of bias of the included RCTs. Data aggregation and risk of bias evaluation were conducted on Review Manager Version 5.3. The protocol was registered in the PROSPERO database (CRD42016037543). A total of 28 RCTs involving 1747 patients (883 patients in the treatment group and 864 patients in the control group) were included in the quantitative synthesis. The results demonstrated significant effects of acupuncture in improving PSA functional communication (P

Purpose Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123I]-VEGF scintigraphy in patients with histologically verified brain tumors. Methods 23 consecutive patients (9 women and 14 men aged 30–83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study. All patients had undergone [123I]-VEGF scintigraphy. SPECT examinations of brain were performed 30 min and 18 h after injection. Additional [11C]-methionine PET ([11C]-MET PET) was performed in eight of the 23 patients. Both [123I]-VEGF and [11C]-MET PET were evaluated visually and semiquantitatively by tumor-to-normal brain uptake ratio (T/N ratio). Thresholds of the T/N ratio were evaluated by analysis of receiver operating characteristics (ROC). Overall survival (OS) was estimated using the Kaplan-Meier method. Results World Health Organization (WHO) grade IV glioma lesions showed [123I]-VEGF uptake 18 h after the injection, whereas other brain tumors of grade II or III showed negative results. There was no significant difference in the tumor size between VEGF positive and VEGF negative tumors. Patients with [123I]-VEGF T/N ratio threshold

To explore the relativity between heart-brain and post-stroke anxiety disorder by analyzing the pathogenesis of post-stroke anxiety disorder combined with the physiology and pathology of organs. The acupoint selection thought was explored by its selection rule according to literature. Post-stroke anxiety belongs to the brain organic anxiety disorder, whose basic pathogenesis is mind injury. The crucial cause is heart and brain disorder at the same time. Thus, Baihui (GV 20), Fengfu (GV 16) for brain and Xinshu (BL 15), Shenmen (HT 7) for heart can improve anxiety disorder according to the theories such as five organ

To explore the specifificity of Tongli (HT 5) and Xuanzhong (GB 39) paired acupionts in aspects of Deqi sensation and brain activation patterns during electroacupuncture. In this study, 15 healthy subjects were enrolled. All participants suffered two kinds of functional magnetic resonance imaging (fMRI) examinations randomly: Examination A received electro-acupuncture (EA) at the bilateral Tongli (HT5) and Xuanzhong (GB 39) acupoints (ACU), and examination B received EA at bilateral non-acupoints (NAP). The subjects reported the feeling of Deqi at each examination later respectively. A multi-voxel pattern analysis method and Statistical Program for Social Sciences were used to analyze the data. The ACU group (Exam A) reported fullness, heaviness, numbness, soreness and throbbing of signifificantly greater intensity than the NAP group (Exam B). In addition, there was no statistical signifificance between two groups in aching, tingling, deep pressure, sharp pain, dull pain, warmness and cold. Meanwhile, fMRI data revealed differences between two groups in discriminating accuracy of brain somatosensory cortex and language-related cortices. Needling HT 5 and GB 39 may modulate language function through a complex brain network, suggesting that it may be benefificial to the recovery of language function in patients with aphasia.

Redox homeostasis has been implicated in subarachnoid hemorrhage (SAH). As a result, antioxidants and/or free radical scavengers have become an important therapeutic modality. Considering that radix trichosanthis (RT) saponins exhibited strong antioxidant ability bothin vivoandin vitro, the present study aimed to reveal whether the neuroprotective activities of RT saponins were mediated by p38/p53 signal pathway after SAH. An established SAH model was used and superoxide dismutase (SOD), malondialdehyde (MDA), induced nitric oxide synthase (iNOS), nitric oxide (NO), lactate dehydrogenase (LDH), p-p38, and p53 activation were detected after 48 h of SAH. The results showed that RT saponins inhibited iNOS expression to restore NO to basal level. Moreover, compared with Cu/Zn-SOD, RT saponins (2 mg/kg/d dosage) significantly increased Mn-SOD activity after SAH. Accompanied with lowered NO and elevated SOD, decreased p38 phosphorylation and p53 activities were observed, especially for RT saponins at 2 mg/kg/d dosage. In this setting, the neurological outcome was also improved with less neuronal cells damage after RT saponins pretreatment. Our findings demonstrated the beneficial effects of RT saponins in enhancing neuroprotective effects by deducing iNOS activity, normalizing SOD level, and inhibiting p-p38 and p53 expression, hence offering significant therapeutic implications for SAH.

Language is an essential higher cognitive function supported by large-scale brain networks. In this study, we investigated functional connectivity changes in the left frontoparietal network (LFPN), a language-cognition related brain network in aphasic patients. We enrolled thirteen aphasic patients who had undergone a stroke in the left hemisphere and age-, gender-, educational level-matched controls and analyzed the data by integrating independent component analysis (ICA) with a network connectivity analysis method. Resting state functional magnetic resonance imaging (fMRI) and clinical evaluation of language function were assessed at two stages: one and two months after stroke onset. We found reduced functional connectivity between the LFPN and the right middle frontal cortex, medial frontal cortex and right inferior frontal cortex in aphasic patients as compared to controls. Correlation analysis showed that stronger functional connectivity between the LFPN and the right middle frontal cortex and medial frontal cortex coincided with more preserved language comprehension ability after stroke. Network connectivity analysis showed reduced LFPN connectivity as indicated by the mean network connectivity index of key regions in the LFPN of aphasic patients. The decreased LFPN connectivity in stroke patients was significantly associated with the impairment of language function in their comprehension ability. We also found significant association between recovery of comprehension ability and the mean changes in intrinsic LFPN connectivity. Our findings suggest that brain lesions may influence language comprehension by altering functional connectivity between regions and that the patterns of abnormal functional connectivity may contribute to the recovery of language deficits.

Determining an appropriate control for use in acupuncture research remains one of the largest methodological challenges acupuncture researchers face. In general, acupuncture controls fall under one of two categories: (1) sham acupuncture, in which the skin is punctured with real acupuncture needles either fully at nonacupoint locations or shallowly at acupoint locations or both and (2) placebo acupuncture, which utilizes nonpenetrating acupuncture devices. In this study, we will focus on non-penetrating placebo acupuncture devices (blunted-needle and nonneedle devices) that are currently available in acupuncture research. We will describe each device and discuss each device’s validation and application in previous studies. In addition, we will outline the advantages and disadvantages of these devices and highlight how the differences among placebo devices can be used to isolate distinct components of acupuncture treatment and investigate their effects. We would like to emphasize that there is no single placebo device that can serve as the best control for all acupuncture studies; the choice of an acupuncture control should be determined by the specific aim of the study.