Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.

Introduction: To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Methods: Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. Results: After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. Conclusion: SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

The altered intrinsic functional connectivity after acupuncture at shenmen (HT7) in acute sleep deprivation.

Introduction: Accumulating evidence has shown that acupuncture could significantly improve the sleep quality and cognitive function of individuals suffering from insufficient sleep. Numerous animal studies have confirmed the effects and mechanisms of acupuncture on acute sleep deprivation (SD). However, the role of acupuncture on individuals after acute SD remains unclear. Methods: In the current study, we recruited 30 healthy subjects with regular sleep. All subjects received resting-state fMRI scans during the rested wakefulness (RW) state and after 24 h of total SD. The scan after 24 h of total SD included two resting-state fMRI sessions before and after needling at Shenmen (HT7). Both edge-based and large-scale network FCs were calculated. Results: The edge-based results showed the suprathreshold edges with abnormal between-network FC involving all paired networks except somatosensory motor network (SMN)-SCN between the SD and RW state, while both decreased and increased between-network FC of edges involving all paired networks except frontoparietal network (FPN)-subcortical network (SCN) between before and after acupuncture at HT7. Compared with the RW state, the large-scale brain network results showed decreased between-network FC in SMN-Default Mode Network (DMN), SMN-FPN, and SMN-ventral attention network (VAN), and increased between-network FC in Dorsal Attention Network (DAN)-VAN, DAN-SMN between the RW state and after 24 h of total SD. After acupuncture at HT7, the large-scale brain network results showed decreased between-network FC in DAN-VAN and increased between-network FC in SMN-VAN. Conclusion: Acupuncture could widely modulate extensive brain networks and reverse the specific between-network FC. The altered FC after acupuncture at HT7 may provide new evidence to interpret neuroimaging mechanisms of the acupuncture effect on acute SD.

Disrupted Resting-State Functional Connectivity between the Dorsal Attention, Default Mode, and Frontoparietal Networks in Nonorganic Gastrointestinal Disorder Patients with Spleen Deficiency Syndrome.

INTRODUCTION: Spleen deficiency syndrome (SDS), a common clinical syndrome of traditional Chinese medicine, is manifested with digestive symptoms and cognitive impairments. However, the cognitive neural mechanism in brain networks of SDS still remained unclear. Our aim was to investigate the changes between the default mode, dorsal attention, and frontoparietal networks in SDS. METHODS: Twenty nonorganic gastrointestinal disorder (NOGD) patients with SDS and eighteen healthy controls were enrolled to attend functional magnetic resonance imaging scan and participated a continuous performance test (CPT) before scanning. RESULTS: Compared with healthy controls, NOGD patients with SDS showed the significantly increased functional connectivity (FC) between dorsal attention network (DAN) and left frontal-parietal control network (LFPN) and significantly decreased FC between LFPN and default mode network (DMN). The functional network connectivity analysis showed positive correlation coefficients between the DAN and LFPN and DAN and DMN as well as negative correlation between LFPN and DMN in NOGD patients with SDS compared with healthy controls. Correlation analysis revealed that the increased FC between LFPN and DAN was positively correlated with 4-digitnumber reaction time mean (RTM) and 3-digitnumber RTM. CONCLUSION: Our study may provide novel insights into the relationship among the DMN, DAN, and FPN in NOGD patients with SDS to deepen our understanding of the neuropsychological mechanisms of SDS.

Shi-Zhen-An-Shen Decoction, a Herbal Medicine That Reverses Cuprizone-Induced Demyelination and Behavioral Deficits in Mice Independent of the Neuregulin-1 Pathway.

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n = 10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

Acupuncture Modulates Disrupted Whole-Brain Network after Ischemic Stroke: Evidence Based on Graph Theory Analysis.

Background: Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. Methods: 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Results: Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (E g), and the mean local efficiency (E loc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and E loc. Acupuncture improved the patients' clustering coefficient (C p) and E loc but did not make a significant impact on the σ and E g. The postacupuncture variables of the whole-brain network had no association with the time of onset. Conclusion: The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.

The fMRI study for acupuncture on shift work sleep disorder: Study protocol for a randomized controlled neuroimaging trial.

INTRODUCTION: Nearly 20% of night shift nurses will cause shift work disorder (SWD) due to the disruption of sleep-wake cycle, which not only affects the daily work efficiency, but also brings a huge burden on physical and mental health. Acupuncture is a safe and effective intervention on SWD. This trial will combine with functional magnetic resonance imaging (fMRI) to study the clinical effects and potential mechanism of acupuncture in the treatment of SWD. METHODS AND ANALYSIS: This is a randomized controlled neuroimaging trial, with enrolled participants, outcome assessors, and data statisticians blinded. 60 patients with SWD and 30 healthy controls who sleep regularly will be recruited and divided into divided into a control group, a true acupoints treatment group (TATG) and a sham acupoints treatment group (SATG) by the ratio of 1:1:1. The TATG and SATG will receive 8 sessions of acupuncture treatment in 4 weeks. Cognitive function scales and MRI scanning will be performed before and after 4-week acupuncture treatment. The control group will receive no intervention. Functional connectivity of intra-network and inter-network will be the primary outcome and effect indicator. The secondary outcomes included Repeatable Battery for the Assessment of Neuropsychological Status, Attentional Network Test, Pittsburgh Sleep Quality Index scale and needle sensation assessment scale. Neuroimage indicators will be correlated with clinical data and scores of cognitive function assessment to explore the possible mechanisms underlying the changes of brain activity caused by acupuncture treatment. DISCUSSION: The results of this study will enable us to verify the therapeutic effect of acupuncture on SWD and explore the potential central mechanism of acupuncture on SWD from the change of brain activity.

Efficacy and safety of Shu-gan-qing-re formula for generalized anxiety disorder: study protocol for a multi-center, prospective, double-blind, double-dummy, randomized controlled trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a persistent and common mental disorder that entails significant impairments in role functioning and quality of life. Currently available effective interventions include psychological therapies, self-help approaches, and pharmacological treatments, which do not quite meet clinical needs, and the ideal anxiolytic is still being sought. Shu-gan-qing-re (SGQR) formula, a Chinese patent medicine, has been well received by patients with GAD in Chinese clinical practice for years. The present prospective, double-blind, double-dummy, randomized controlled trial is designed to investigate the efficacy and safety of SGQR formula for GAD. METHODS/DESIGN: A total of 200 eligible participants will be recruited from four hospitals in different parts of China. They will be randomly assigned to either the study group or the control group in a ratio of 1:1. Participants allocated to the study group will receive SGQR formula and buspirone placebo, while buspirone and SGQR placebo will be applied in the control group. Six scheduled visits will be conducted over the course of 8 weeks. Outcome measurements include Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale-17 (HAMD-17), Clinical Global Impression-Improvement Scale (CGI-I), Traditional Chinese Medicine Syndrome Scale for GAD, and pro-inflammatory cytokine tests: interleukin-1 beta (IL-1ß), IL-6, and tumor necrosis factor-alpha. Adverse reactions will be evaluated by using the Treatment Emergent Symptom Scale (TESS). Safety outcomes and adverse events will also be recorded. DISCUSSION: The study will provide scientific and objective assessments for the efficacy and safety of SGQR formula for patients with GAD, hopefully offering clinicians an alternative approach to GAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IPR-17013058. Registered on October 20, 2017.

Efficacy and safety of electroacupuncture on metabolic syndrome due to olanzapine and risperidone: Study protocol for a randomized controlled pilot trial.

INTRODUCTION: With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone. METHODS: This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months' follow-up. DISCUSSION: The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.

Acupuncture Enhances Communication between Cortices with Damaged White Matters in Poststroke Motor Impairment.

Stroke is a leading cause of motor disability. Acupuncture is an effective therapeutic strategy for poststroke motor impairment. However, its mechanism is still elusive. Twenty-two stroke patients having a right-hemispheric subcortical infarct and 22 matched healthy controls were recruited to undergo diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scanning. The resting-state fMRI was implemented before and after needling at GB34 (Yanglingquan). The stroke patients presented a substantially reduced fractional anisotropy value in the right superior longitudinal fasciculus (SLF), corticospinal tract, and corpus callosum. The structural integrity of the frontoparietal part of the SLF (SLF-FP) correlated with the motor scores of lower limbs in stroke patients. This corticocortical association bundle originated from the premotor cortex (PM) and the adjacent supplementary motor area (SMA), known as secondary motor areas, and terminated in the supramarginal gyrus (SMG). After acupuncture intervention, the corresponding functional connectivity between the PM/SMA and SMG was enhanced in stroke patients compared with healthy controls. These findings suggested that the integrity of the SLF is a potential neuroimaging biomarker for motor disability of lower limbs following a stroke. Acupuncture could increase the communication between the cortices connected by the impaired white matter tracts, implying the neural mechanism underlying the acupuncture intervention.

Enhanced Functional Connectivity between the Bilateral Primary Motor Cortices after Acupuncture at Yanglingquan (GB34) in Right-Hemispheric Subcortical Stroke Patients: A Resting-State fMRI Study.

Increasing neuroimaging researches in stroke rehabilitation had revealed the neural mechanisms of rehabilitation therapy. However, little was known about the neural mechanisms of acupuncture therapy in subcortical stroke patients. The aim of this study was to investigate the changes of functional connectivity (FC) between the bilateral primary motor cortices (M1s) after acupuncture intervention in right subcortical stroke patients. Twenty right-hemispheric subcortical stroke patients and 20 healthy subjects were recruited to undergo one functional magnetic resonance imaging (fMRI) scanning. The scanning consisted of resting-state fMRI before and after needling at Yanglinquan (GB34), and task-evoked fMRI. The most significant active point during the left passive thumb-to-index task was chosen as the seed point. The seed-based FC analysis of the bilateral M1s was performed. Stroke patients revealed decreased FC between the bilateral M1s compared with healthy subjects, and the decreased FC was significantly enhanced after acupuncture at GB34. Acupuncture could increase the intrinsically decreased FC between the bilateral M1s which provided further insight into the neural mechanisms of acupuncture for motor function recovery in stroke patients.

A case study of Ramsay Hunt Syndrome in conjunction with cranial polyneuritis.

RATIONALE: Ramsay Hunt syndrome in conjunction with cranial polyneuritis is not extensively documented, and is very easily misdiagnosed. PATIENT CONCERNS: A case of a 53-year-old male with Ramsay Hunt syndrome in conjunction with cranial polyneuritis is presented with early symptoms of vertigo, cephalalgia, and facial palsy, followed by zoster oticus 10 days later. DIAGNOSES: Diagnosis was challenging as this condition presents with multiple neuropathies, and attempting to diagnose based on clinical symptoms was often misleading. Polymerase chain reaction can be used to test for presence of the virus in the cerebrospinal fluid, followed by targeted drug therapy. INTERVENTIONS: Acupuncture, in conjunction with fire cupping, bloodletting around the afflicted region on the face, as well as oral consumption of herbal medicine and vitamins for nerve nourishment was given to treat this disease. OUTCOMES: Due to misdiagnosis resulting in delayed treatment, peripheral facial paralysis was left as the main sequelae, while other symptoms responded quickly to treatment. After a 6-month follow-up, facial palsy was still present. LESSONS: Considering that targeted antiviral therapy can be used to increase the effectiveness of treatment, early diagnosis, and timely use of medication is critical.

Altered effective connectivity of resting state networks by acupuncture stimulation in stroke patients with left hemiplegia: A multivariate granger analysis.

The aim of this study was to explore the response feature of resting-state networks (RSNs) of stroke patients with left hemiplegia by acupuncture stimulation.Nineteen stroke patients with left hemiplegia and 17 controls were recruited in this study. Resting-state functional magnetic resonance imaging data before and after acupuncture were acquired using magnetic scanning. The independent component analysis (ICA) was employed to extract RSNs related to motion, sensation, cognition, and execution, including sensorimotor network (SMN), left and right frontoparietal network (LFPN and RFPN), anterior and posterior default mode network (aDMN, pDMN), visual network (VN), and salience network (SN). Granger causality method was used to explore how acupuncture stimulation affects the causality between intrinsic RSNs in stroke patients. Compared with healthy subjects, stroke patients presented the more complex effective connectivity. Before acupuncture stimulation, LFPN inputted most information from other networks while DMN outputted most information to other networks; however, the above results were reversal by acupuncture. In addition, we found aDMN reside in between SMN and LFPN after acupuncture.The finding suggested that acupuncture probably integrated the effective connectivity internetwork by modulating multiple networks and transferring information between LFPN and SMN by DMN as the relay station.

The biomechanical effect of acupuncture for poststroke cavovarus foot: study protocol for a randomized controlled pilot trial.

BACKGROUND: Poststroke cavovarus foot greatly affects patients' activities of daily life and raises the risks of falls and consequent fractures. Acupuncture appears to be safe and effective in promoting motor functions and enhancing the activities of daily life among patients with poststroke cavovarus foot. The current study aims to study the biomechanical effect of acupuncture for poststroke cavovarus foot with objective outcome measurements. METHODS/DESIGN: This is an assessor and analyst-blinded, randomized, controlled pilot study. A total of 60 eligible patients with poststroke cavovarus foot will be allocated by a 1:1 ratio into an acupuncture treatment group and a control group. Patients in the control group will receive conventional rehabilitation therapies, whereas a combination of acupuncture and conventional rehabilitation therapies will be applied in the acupuncture group. The primary outcome measures are three objective biomechanical parameters from the RSSCAN gait system: varus angle, dynamic plantar pressure distribution, and static plantar contact area. Scores of the Berg Balance Scale, the Fugl-Meyer Assessment, and the Stroke-Specific Quality of Life Scale, as well as other biomechanical parameters such as the step length and width, step time phase, and weight shifting phase will be selected as secondary outcome measurements. All assessments will be conducted at baseline, 4 weeks after the treatment course, and after a follow-up period of 3 months. DISCUSSION: Results of the current study will provide detailed interpretations of the biomechanical effect of acupuncture for stroke rehabilitation and foundations for future larger clinical studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IPC-15006889 (8 August 2015).

The effects of acupuncture treatment on the right frontoparietal network in migraine without aura patients.

BACKGROUND: Functional and structural abnormalities in resting-state brain networks in migraine patients have been confirmed by previous functional magnetic resonance imaging (fMRI) studies. However, few studies focusing on the neural responses of therapeutic treatment on migraine have been conducted. In this study, we tried to examined the treatment-related effects of standard acupuncture treatment on the right frontoparietal network (RFPN) in migraine patients. METHODS: A total of 12 migraine without aura (MWoA) patients were recruited to undergo resting-state fMRI scanning and were rescanned after 4 weeks standard acupuncture treatment. Another 12 matched healthy control (HC) subjects underwent once scanning for comparison. We analyzed the functional connectivity of the RFPN between MWoA patients and HC subjects before treatment and that of the MWoA patients before and after treatment. Diffusion tensor images (DTI) data analyzing was also performed to detect fiber-related treatment responses. RESULTS: We observed significantly decreased FC in the RFPN and that the decreased FC could be reversed by acupuncture treatment. The changes of FC in MWoA patients was negatively correlated with the decrease of visual analogue scale (VAS) scores after treatment. This study indicated that acupuncture treatment for MWoA patients was associated with normalizing effects on the intrinsic decreased FC of the RFPN. CONCLUSIONS: Our study provided new insights into the treatment-related neural responses in MWoA patients and suggested potential functional pathways for the evaluation of treatment in MWoA patients. Future studies are still in need to confirm the current results and to elucidate the complex neural mechanisms of acupuncture treatment.