Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.

BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Acupuncture for cancer-related insomnia: A systematic review and meta-analysis.

BACKGROUND: Cancer-related insomnia is a highly prevalent complaint in cancer patients. However, there is no meta-analytic synthesis explored the efficacy of acupuncture for cancer-related insomnia among cancer patients undergoing active cancer treatments. OBJECTIVE: This systematic review and meta-analysis were performed to explore the efficacy and safety of acupuncture for insomnia in people diagnosed with cancer. STUDY DESIGN: Systematic review and meta-analysis of existing randomized controlled trials on acupuncture in the treatment of cancer-related insomnia. METHODS: According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, we identified and extracted the trials through November 2021 from ten databases and two trials record platforms (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PUBMED, Web of Science, PsycINFO, Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Digital Journals, ClinicalTrials, World Health Organization International Clinical Trials Registry Platform). The quality of the trials was assessed using Jadad score and Risk of Bias (2.0). A meta-analysis was synthesized using the random-effects model if the included studies were in high methodological quality. RESULTS: A total of 690 studies were identified, with 22 were included in the review, and 6 of them were included in the quantitative synthesis. Studies were highly heterogeneous in terms of participant characteristics and study methodologies. Most studies recruited patients diagnosed with a specific cancer type, and breast cancer patients were the subgroup most represented. The qualitative review of available evidence suggested a beneficial efficacy of acupuncture on sleep without serious adverse events in several studies (55%). The meta-analysis revealed that acupuncture produced a significant improvement in the total Pittsburgh Sleep Quality Index (PSQI) score relative to the wait-list control among breast cancer patients undergoing active cancer treatments (MD -1.92, 95% CI -3.25 to -0.59, p = 0.005). Similar improvement of real and sham acupuncture on PSQI score change post-intervention was found (MD: -0.68, 95% CI: -2.44 to 1.07, p = 0.44). Manual acupuncture had similar effective rate as compared to estazolam immediately post-intervention (RR: 0.94, 95% CI: 0.87 to 1.01, p = 0.09), and had significantly better effective rate than estazolam at 1-week post-intervention follow-up (RR: 1.25, 95% CI: 1.10 to 1.43, p = 0.0009). All reported acupuncture related adverse events were mild or moderate in severity. CONCLUSION: Acupuncture has great potential to be used to manage cancer-related insomnia for cancer patients or survivors. More studies with rigorous designs and larger sample size are warranted to verify the efficacy and safety of acupuncture for insomnia among people diagnosed with cancer, in particular among those with clinically significant insomnia. REGISTRATION: PROSPERO (ID: CRD42021285844).

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. CONCLUSIONS: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Acupuncture for insomnia after ischemic stroke: an assessor-participant blinded, randomized controlled trial.

BACKGROUND: To date, there has been little focus on research into acupuncture for insomnia after ischemic stroke. Insomnia is one of the most common sequelae after ischemic stroke, and it is the most unrecognized modifiable risk factor. OBJECTIVE: To evaluate the efficacy and safety of acupuncture for insomnia after ischemic stroke. METHODS: In this assessor-participant blinded, randomized, controlled trial, 144 ischemic stroke patients with insomnia meeting Diagnostic and Statistical Manual of Mental Disorders (fifth edition, DSM-5) criteria were assigned to verum or sham acupuncture treatment (n = 72 per group) for three sessions per week over 4 weeks. The outcomes were the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), stroke-specific quality of life (SSQoL), and Hospital Anxiety and Depression Scale (HADS) scores. Multiple objective sleep variables were recorded using actigraphy. Assessment was conducted at baseline, and thereafter once biweekly for the 4-week treatment and at 4 weeks of follow-up. RESULTS: The verum acupuncture group had significantly greater improvements than the sham acupuncture group in sleep quality from 2 weeks into treatment throughout the follow-up, indicated by ISI scores and actigraphic variable SE (sleep efficiency). This greater improvement was also observed in the PSQI after 4 weeks of treatment throughout follow-up, as well as actigraphic variable TST (total sleep time), SSQoL and HADS scores at the end of treatment, and SSQoL and depression scores at follow-up. There was no significant difference between groups in the actigraphic variable SA (sleep awakenings). Adverse events were mild in severity, and their incidence was not significantly different between the two groups. CONCLUSION: Acupuncture appears to be efficacious, in terms of improving insomnia, related quality of life, and affective symptoms, for patients with ischemic stroke. TRIAL REGISTRATION NUMBER: ChiCTR-IIC-16008382 (Chinese Clinical Trial Registry).

Self-administered acupressure for insomnia disorder: A randomized controlled trial.

BACKGROUND: Insomnia is a significant health problem in the community. Self-administered acupressure (SAA) may be an alternative strategy to alleviate insomnia. PURPOSE: This study is the first to investigate the effects of SAA delivered through a training course in alleviating insomnia disorder compared with sleep hygiene education (SHE). METHODS: A randomized controlled trial was conducted on 200 participants with insomnia disorder. The eligible participants were randomized into the SAA or SHE group. Both groups attended the allocated training courses (two sessions, 2 h each) and then were followed up at weeks 4 and 8. The primary outcome was the severity of insomnia symptoms and related daytime impairment as measured by the Insomnia Severity Index (ISI). Other measures included a 7-day sleep diary and actigraphy, Hospital Anxiety and Depression Scale (HADS), and Short-Form Six-Dimension (SF6D). RESULTS: The SAA group showed a significantly greater improvement in ISI score than the SHE group at week 4 (mean difference: -1.89 units, 95% CI: 0.85, 2.93; Cohen's d = 0.51, p < 0.001) and week 8 (mean difference: -2.89 units, 95% CI: 1.67, 4.11; d = 0.67, p < 0.001). In addition, the SAA group showed a greater reduction in the HADS anxiety score and HADS depression score and increase in SF6D at week 8. CONCLUSIONS: SAA taught in a short training course is a feasible and effective approach to improve sleep and related daytime impairment and mood problems in individuals with insomnia disorder.

Granatin B and punicalagin from Chinese herbal medicine pomegranate peels elicit reactive oxygen species-mediated apoptosis and cell cycle arrest in colorectal cancer cells.

BACKGROUND: Colorectal cancer ranks among the most common cancers. 5-Fluorouracil (5-FU) based first-line chemotherapy for colorectal cancer treatment often leads to chemoresistance and gastrointestinal mucositis. PURPOSE: This study aimed to find potential therapeutic agents from herbal medicine with anti-colorectal cancer and anti-mucositis activities. METHODS: Chinese medicine theory, network pharmacology analyses, and antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses were used to identify potential bioactive compounds. HT-29 human colorectal cancer cell culture and xenograft tumor models were employed to study anti-colorectal cancer efficacy. Lipopolysaccharide-induced RAW 264.7 and 5-FU treated Dark Agouti rats were used to evaluate anti-inflammatory and anti-mucositis activities. Histological staining, immunofluorescence imaging, western blots, and flow cytometric analyses were employed to explore the underlying mechanisms. RESULTS: Both Chinese medicine theory and network pharmacology analyses indicated pomegranate peels as a potential anti-colorectal cancer and anti-mucositis agent. Antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses revealed granatin B and punicalagin as the most potent antioxidant compounds in pomegranate peels. Granatin B and punicalagin demonstrated superior anti-colorectal cancer activities in both cell culture and xenograft tumor models. Granatin B and punicalagin also exhibited strong anti-inflammatory activities in lipopolysaccharide-induced RAW264.7 cells and anti-mucositis activities in 5-FU-treated rats. Mechanistic studies revealed that granatin B and punicalagin induced reactive oxygen species-mediated S-phase cell cycle arrest and apoptosis in HT-29 cells. Moreover, these compounds sensitized HT-29 cells to 5-FU-induced cell death and S-phase cell cycle arrest. CONCLUSION: We report that granatin B and punicalagin exhibit superior anti-colorectal cancer and anti-mucositis activities. To the best of our knowledge, these results are novel and suggest that utilizing phenols from herbal medicine, such as granatin B and punicalagin, to target reactive oxygen species may be an innovative therapy to treat colorectal cancer and intestinal mucositis.

Chinese Medicine for Coronavirus Disease 2019 (COVID-19): A GRADE-Assessed Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) has caused enormous public health and socioeconomic burden globally. This study aims to evaluate the efficacy and safety of Chinese medicine (CM) against COVID-19. Eleven databases were searched on April 30, 2021, and 52 studies were included. The RoB 2.0, ROBINS-I, and GRADE tools were employed to assess the risks and evidence grades. The findings with moderate certainty in GRADE showed that compared with routine treatment (RT), Lianhua Qingwen granules (LHQW) adjunctive to RT showed significantly improved efficacy rate (relative risk (RR) = 1.19, 95% confidence interval (CI): [1.09, 1.31]), febrile score (standard mean difference (SMD) = -1.21, 95% CI: [-1.43, -0.99]), and computerized tomography (CT) lung images (RR = 1.23, 95% CI: [1.10, 1.38]); Qingfei Paidu decoction (QFPD) plus RT significantly shortened the length of hospital stay (SMD = -1.83, 95% CI: [-2.18, -1.48]); Feiyan Yihao formula (FYYH) plus RT significantly improved the clinical efficacy rate (RR = 1.07, 95% CI: [1, 1.15]), febrile time (SMD = -0.02, 95% CI: [-0.23, 0.19]), and time to negative PCR test for COVID-19 (SMD = -0.72, 95% CI: [-0.94, -0.51]). Adjunctive effects of CM with lower certainty of evidence were found, including the improvements of symptoms, laboratory findings, and mortality. No or mild adverse events were observed in most of the studies. In conclusion, the current evidence indicates that CM formulae, particularly LHQW, QFPD, and FYYH, have adjunctive effects on the standard treatment of COVID-19.

Randomized double-blind trial comparing low dose and conventional dose of a modified traditional herbal formula Guizhi Fuling Wan in women with symptomatic uterine fibroids.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Guizhi Fuling Wan is one common remedy for treating uterine fibroids (UFs) and the relevant symptoms in Traditional Chinese Medicine (TCM). Previous systematic reviews showed that Guizhi Fuling Formula appeared to have additional benefit based on mifepristone treatment in reducing volume of fibroids. AIM OF STUDY: To study the efficacy and safety of the conventional dose of a modified herbal formula Guizhi Fuling Wan in patients with symptomatic uterine fibroids in comparison with a sub-effective dose control. MATERIALS AND METHODS: This randomized double-blind, dosage-controlled trial was carried out in an outpatient clinic of traditional Chinese medicine in Hong Kong. Women with symptomatic uterine fibroids diagnosed according to the WHO International Classification of Diseases (ICD-10) were recruited and randomly assigned to one of two groups that received modified Guizhi Fuling Wan at either a low dose or the conventional dose on a daily basis for 16 weeks. This study was quality controlled by a data safety monitoring board. The primary outcome was the symptom severity as measured with the Uterine Fibroid Symptom-Quality of Life questionnaire. The secondary outcomes included quality of life, menstrual bleeding (measured on a pictorial blood loss assessment chart), pain severity (measured on the 6-point behavioral rating scale), change in Chinese medicine syndrome score, fibroid volume (measured by magnetic resonance imaging), hemoglobin level, and hormone levels. RESULTS: Seventy-eight women were recruited for this study. Between-groups comparison showed no significant difference at the endpoint for all outcomes except for the Chinese medicine syndrome score; however, at the endpoint, within-group comparison showed significant improvement in both groups relative to baseline in symptom severity, functional influence of pelvic pain, Chinese medicine syndrome score, and fibroid volume and uterus condition on magnetic resonance imaging (p < 0.05).The low-dose group yielded greater endpoint improvement in the Chinese medicine syndrome score than the conventional-dose group (p=0.024). No serious adverse events related to the intervention were noted. CONCLUSION: Both low-dose and conventional-dose preparations significantly ameliorated uterine fibroid-related symptoms and fibroid volume, although no significant difference was found between the low-dose and conventional-dose groups. The herbal formula GuizhiFuling Wan is safe in women with uterine fibroids.

Adiponectin regulates electroacupuncture-produced analgesic effects in association with a crosstalk between the peripheral circulation and the spinal cord.

Neurotransmitter-mediated acupuncture analgesia has been widely studied in nervous systems. It remains largely unclear if peripheral substances are involved the acupuncture analgesia. Adiponectin (APN), a circulating adipokine, shows analgesic effects. The study aimed to examine whether APN regulates analgesic effects of electroacupuncture (EA) in the complete Freund's adjuvant (CFA)-induced mouse model. APN wild type (WT) and knockout (KO) mouse were employed in the study. We found that EA attenuates the CFA-induced pain as demonstrated by the Hargreaves thermal test and the von Frey filament test. The deletion of APN significantly reduced the acupuncture analgesia in the CFA-treated APN KO mice while the intrathecal administration of APN mimicked the analgesic effects of EA. We further revealed that EA produced analgesic effects mainly via APN/AdipoR2-mediated AMPK pathway by the siRNA inhibitions of APN receptors (adipoR1/2) in the spinal cord. The immunofluorescence staining analysis showed that EA increased the APN accumulation in spinal cord through the blood circulation. In conclusion, the study indicates a novel mechanism that acupuncture produces analgesic effects at least partially via APN/AdipoR2-AMPK pathway in the spinal cord.

Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress.

Acute myocardial infarction (AMI) has been a preclinical and clinical concern due to high hospitalization rate and mortality. This study was aimed at evaluating the effectiveness and safety of Shexiang Baoxin Pill (SBP) for AMI and exploring the possible mechanism of oxidative stress. Six databases were searched on March 26, 2021. Twenty-four studies were included and accessed by the RoB 2.0 or SYRCLE tool. Compared with routine treatment (RT), SBP showed the effectiveness in the clinical efficacy (RR = 1.15, 95% CI [1.06, 1.25]), left ventricular ejection fraction (LVEF) (SMD = 0.73, 95% CI [0.62, 0.95]), glutathione (GSH) (SMD = 2.07, 95% CI [1.51, 2.64]), superoxide dismutase (SOD) (SMD = 0.92, 95% CI [0.58, 1.26]), malondialdehyde (MDA) (SMD = -4.23, 95% CI [-5.80, -2.66]), creatine kinase-myocardial band (CK-MB) (SMD = -4.98, 95% CI [-5.64, -4.33]), cardiac troponin I (cTnI) (SMD = -2.17, 95% CI [-2.57, -1.76]), high-sensitivity C-reactive protein (Hs-CRP) (SMD = -1.34, 95% CI [-1.56, -1.12]), interleukin-6 (IL-6) (SMD = -0.99, 95% CI [-1.26, -0.71]), triglycerides (TG) (SMD = -0.52, 95% CI [-0.83, -0.22]), flow-mediated dilation (FMD) (SMD = 1.39, 95% CI [1.06, 1.72]), von Willebrand Factor (vWF) (SMD = -1.77, 95% CI [-2.39, -1.15]), nitric oxide (NO) (SMD = 0.89, 95% CI [0.65, 1.13]), and recurrent rate (RR = 0.30, 95% CI [0.15, 0.59]). But SBP adjunctive to RT plus PCI had no improvements in almost pooled outcomes except for the Hs-CRP (SMD = -1.19, 95% CI [-1.44, -0.94]) and TG (SMD = -0.25, 95% CI [-0.48, -0.02]). Laboratory findings showed that SBP enhanced the endothelial nitric oxide synthase (eNOS) activity and regulated laboratory indexes especially for homocysteine. In conclusion, SBP has adjunctive effects on AMI via the mechanism of antioxidative stress. The current evidence supports the use of SBP for mild and moderate AMI patients.

Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial.

OBJECTIVE: Insomnia is a highly prevalent and disturbing symptom in breast cancer patients under or post chemotherapy. If not appropriately treated, it can persist for years after the completion of cancer treatments. Acupuncture has been widely used for alleviating insomnia. The aim of this study is to examine the feasibility, efficacy and safety of acupuncture for chemotherapy-related insomnia among patients with breast cancer. MATERIALS AND METHODS: This is a trial protocol for a randomized, sham-controlled, subject- and assessor-blinded clinical trial. A total of 138 eligible participants will be assigned randomly to acupuncture or sham control group at a ratio of 1:1. Participants in acupuncture group will receive electroacupuncture (EA) plus auricular acupressure (AA) treatment, while subjects in sham acupuncture group will receive sham EA plus sham AA. Both acupuncture and sham treatments will be given twice weekly for 6 weeks, followed by maintenance treatments once every 4 weeks for 12 weeks (15 sessions totally). The primary outcome is the change of Insomnia Severity Index score between baseline and the end of 6-week treatment. Secondary outcome measurements include Actiwatch, sleep diary, Pittsburgh Sleep Quality Index, Functional Assessment of Cancer Therapy-Breast Cancer, Hospital Anxiety and Depression Scale, Brief Pain Inventory-Short Form, Brief Fatigue Inventory, Acupuncture Expectancy Scale, credibility, and adverse events. Participants will be followed up to 42 weeks. CONCLUSIONS: This trial will expand our understanding of the feasibility, efficacy, and safety of acupuncture as a treatment for alleviating chemotherapy-related insomnia in patients with breast cancer. EA plus AA, if proven to be effective, can be implemented into routine settings to play a role in insomnia management for patients with breast cancer.

Antidepressant Monotherapy and Combination Therapy with Acupuncture in Depressed Patients: A Resting-State Functional Near-Infrared Spectroscopy (fNIRS) Study.

Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3 weeks, while the control group took antidepressants monotherapy for 3 weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of -0.4 and -0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10-20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.

Semi-Individualized Acupuncture for Insomnia Disorder and Oxidative Stress: A Randomized, Double-Blind, Sham-Controlled Trial.

BACKGROUND: Acupuncture is an alternative treatment for improving sleep, and it may attenuate oxidative stress, which is a possible pathophysiological factor in insomnia. The aim of this study was to examine the efficacy and safety of a semi-individualized acupuncture in improving sleep and explore its effect on oxidative stress parameters in adults with insomnia disorder. METHODS: In this randomized sham-controlled trial, 140 participants were randomly assigned to either a 4-week semi-individualized traditional acupuncture (TA) or noninvasive sham acupuncture (SA). The primary outcome measure was the sleep-diary-derived sleep efficiency. Other outcomes included sleep diary and actigraphy, Insomnia Severity Index, anxiety and depressive symptoms, and quality of life. Blood samples were taken to measure oxidative stress parameters (malondialdehyde, glutathione peroxidase, paraoxonase, and arylesterase). RESULTS: Although no significant difference was found in the primary outcome measure, both sleep-diary-derived and actigraphy-derived total sleep time (TST) were significantly increased in the TA group at 1-week posttreatment (mean difference in sleep diary = 22.0 min, p = 0.01, actigraphy = 18.8 min, p = 0.02). At 5-week posttreatment follow-up, a significantly higher proportion of participants in the TA group showed sleep-diary-derived sleep efficiency (SE) ≥ 85% than in the SA group (55.6% versus 36.4%, p = 0.03). CONCLUSION: TA and SA did not significantly differ in improving subjective sleep efficiency in individuals with insomnia disorder. However, the TA group showed a short-term effect on improving TST as measured by both sleep diary and actigraphy at 1-week posttreatment, but there were no differences in the oxidative stress parameters. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Acupuncture in the Modulation of Peripheral Oxidative Stress Insomnia; Identifier NCT03447587; URL: https://clinicaltrials.gov/ct2/show/NCT03447587.

Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity.

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut-brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice. Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting. Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice. Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer's Disease.

Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer's disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aß25-35 served as an in vitro model of Alzheimer's disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml-200 µg/ml, followed by co-incubation with 20 µM Aß25-35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aß-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aß-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aß exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

Electroacupuncture Plus Auricular Acupressure for Chemotherapy-Associated Insomnia in Breast Cancer Patients: A Pilot Randomized Controlled Trial.

OBJECTIVE: Chemotherapy-associated insomnia is a highly prevalent complaint in breast cancer patients. This study was undertaken to evaluate the safety, feasibility, and preliminary effectiveness of electroacupuncture plus auricular acupressure for chemotherapy-associated insomnia in patients with breast cancer. MATERIALS AND METHODS: In this randomized, wait-list controlled trial, thirty breast cancer patients under or post chemotherapy with insomnia were randomly allocated to the acupuncture or wait-list control group. Participants in acupuncture group received electroacupuncture plus auricular acupressure treatment twice weekly for 6 weeks. Participants in wait-list group received the same regimen of treatment after 6-week of waiting period. Insomnia Severity Index (ISI) served as the primary outcome measurement. Secondary outcomes were sleep parameters recorded with sleep diary and actiwatch, as well as the scores of Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B). RESULTS: Twenty-eight participants completed study (13 in the acupuncture group vs 15 in the wait-list control group). At week-6 post-intervention, ISI score change from baseline showed significant between-group difference favoring acupuncture group of -2.9 points (95% CI: -5.2 to -0.6, P = .014). The acupuncture group showed greater improvements in the total sleep time recorded by sleep diary (P = .026), scores of PSQI (P = .012), HADS-depression (P = .020), and FACT-B (P < .001) compared with the control group. Improvements were maintained at week-10 and week-14 follow-ups. CONCLUSIONS: Acupuncture is safe, feasible, and effective for chemotherapy-associated insomnia in breast cancer patients under or post chemotherapy. A larger sample size randomized clinical trial is warranted to confirm the present findings. CLINICAL TRIAL REGISTRATION: NCT03762694.

The Adjunctive Effect of Acupuncture for Advanced Cancer Patients in a Collaborative Model of Palliative Care: Study Protocol for a 3-Arm Randomized Trial.

BACKGROUND: Cancer is the second leading cause of death before the age of 70. Improved cancer survival has put increasing demands on cancer care. Palliative care is the specialized multi-disciplinary care providing relief from the pain, symptoms, and stress of serious illness. The study aims to evaluate the adjunctive effect of acupuncture for advanced cancer patients in a collaborative model of palliative care. METHODS/DESIGN: This is a single-blinded, randomized, sham-controlled trial. One hundred twenty advanced cancer patients undergoing palliative care will be randomized in a ratio of 2:1:1 to manual acupuncture plus standard care group (ASC), sham acupuncture plus standard care group (SSC), and standard care group (SC). Patients in ASC and SSC will receive 9 sessions of acupuncture or sham acupuncture for 3 weeks, and will be followed up for 2 months. The primary measure is the change from baseline score of the Edmonton Symptom Assessment System at 3 weeks. The secondary measures include the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Numeric Rating Scale, and European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care. DISCUSSION: The finding of this trial will provide high-quality evidence on the adjunctive effect of acupuncture to standard care on advanced cancer patients undergoing palliative care. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04398875 (https://www.clinicaltrials.gov/ct2/show/NCT04398875), Registered on 21 May 2020.

Plant-based Medicines (Phytoceuticals) in the Treatment of Psychiatric Disorders: A Meta-review of Meta-analyses of Randomized Controlled Trials: Les médicaments à base de plantes (phytoceutiques) dans le traitement des troubles psychiatriques: une méta-revue des méta-analyses d'essais randomisés contrôlés.

OBJECTIVES: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed "phytoceuticals," in a similar way that medicinal nutrients are termed as "nutraceuticals." Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a "meta-review" of this top-tier evidence. METHODS: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders. RESULTS: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John's wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas' meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias. CONCLUSIONS: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.

Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial.

INTRODUCTION: Diabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD. In vivo and in vitro studies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2-3 CKD and macroalbuminuria, and to identify related response predictors. METHODS AND ANALYSIS: This is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request. TRIAL REGISTRATION NUMBER: NCT03535935.