Efficacy and safety of acupuncture treatment as an adjunctive therapy after knee replacement: Single-center, pragmatic, randomized, assessor blinded, pilot study.

INTRODUCTION: Total knee replacement (TKR) is a surgical procedure that is being increasingly performed as a result of population aging and the increased average human life expectancy in South Korea. Consistent with the growing number of TKR procedures, the number of patients seeking acupuncture for relief from adverse effects, effective pain management, and the enhancement of rehabilitative therapy effects and bodily function after TKR has also been increasing. Thus, an objective examination of the evidence regarding the safety and efficacy of acupuncture treatments is essential. The aim of this study is to verify the hypothesis that the concurrent use of acupuncture treatment and usual care after TKR is more effective, safe, and cost-effective for the relief of TKR symptoms than usual care therapy alone. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial that includes 50 patients with TKR. After screening the patients and receiving informed consent, the patients are divided into two groups (usual care + acupuncture group and usual care group); the patients will then undergo TKR surgery and will be hospitalized for 2 weeks. The patients will receive a total of 8 acupuncture treatments over 2 weeks after surgery and will be followed up at 3, 4, and 12 weeks after the end of the intervention. The primary outcome is assessed using the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), and the secondary outcome is measured using the Numerical Rating Scale (NRS), Risk of Fall, and Range of Motion (ROM). Moreover, the cost per quality-adjusted life years (QALYs) is adopted as a primary economic outcome for economic evaluation, and the cost per NRS is adopted as a secondary economic outcome. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS17ENSS0063). We intend to submit the results to a peer-reviewed journal and/or conferences. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03633097.

Clinical study on concurrent use of electro-acupuncture or Chuna manual therapy with pregabalin for chemotherapy-induced peripheral neuropathy: safety and effectiveness (open-labeled, parallel, randomized controlled trial, assessor-blinded): A study protocol.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects of chemotherapy. Its main symptoms are pain, paresthesia, and numbness. However, the mechanisms underlying the development of CIPN remain unclear and standard treatments have not been established. Recently, there has been a growing interest in various approaches to overcome the limitations of the existing treatments. This study aims to evaluate the efficacy and safety of the concurrent use of two complementary and alternative therapies: electroacupuncture (EA) and Chuna manual therapy (CMT), with pregabalin, which is the conventional pharmacotherapy for neuropathic pain. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial, which includes 90 patients with colorectal and breast cancer, who developed CIPN. After a 2-week preparation period, the patients are divided into three groups (pregabalin administration group, pregabalin + EA treatment group, and pregabalin + CMT treatment group), treated for approximately 5 weeks and followed-up 4 weeks after treatment. The primary outcome is assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale score (version 4.0) and the secondary outcome is measured using the Quality of Life Questionnaire-CIPN 20-Item Scale (version 3.0) and the quality of life questionnaire (version 3.0) developed by the European Organisation for Research and Treatment of Cancer. Moreover, exploratory efficacy and safety evaluations will be conducted based on the chemotherapy-completion rate and nerve conduction studies.

Effect of Samryungbaekchul-san Combined with Otilonium Bromide on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial.

Conventional and herbal drugs are frequently used together to treat many disorders. Samryungbaekchul-san (SRS, a herbal formula) and otilonium bromide (OB, an antispasmodic agent) are widely used to treat diarrhea-predominant irritable bowel syndrome (D-IBS) in Eastern Asian countries. However, there have been no studies on the co-administration of SRS and OB. Therefore, we aimed to preliminarily assess the feasibility of SRS combined with OB for D-IBS treatment in a pilot double-blind, four-arm, parallel-group, randomized controlled trial (RCT), including 80 patients diagnosed with D-IBS according to the Rome III criteria. The patients were randomly assigned to four treatment groups and were administered drugs for eight weeks after a two-week preparatory period. Follow-up was conducted four weeks after the administration period. The primary outcome was evaluated by using a global D-IBS symptom improvement score; no statistically significant difference was observed between the groups. However, multiple logistic regression analysis of primary outcome scores shows that SRS significantly improved D-IBS symptoms (p < 0.05). For secondary outcomes, better results were observed in the SRS + OB group, in terms of symptoms, including abdominal pain, discomfort, frequency of abdominal pain, and stool form than in OB alone or placebo groups (p < 0.05). In conclusion, the co-administration of SRS and OB might be an effective and safe strategy for the treatment of D-IBS. Large-scale RCTs are warranted to further confirm and clarify these findings.

Effect of herbal extract granules combined with otilonium bromide on irritable bowel syndrome with diarrhoea: a study protocol for a randomised controlled trial.

INTRODUCTION: Irritable bowel syndrome (IBS), known as a functional and organic gastrointestinal disorder, is a collection of symptoms that occur together and generally include pain or discomfort in the abdomen and changes in bowel movement patterns. Due to the limitations of conventional treatments, alternative IBS treatments are used by many patients worldwide. Samryungbaekchulsan (SRS), a herbal formula, has long been used for alleviating diarrhoea-predominant IBS (D-IBS) in traditional Korean medicine. Otilonium bromide (OB) is an antimuscarinic compound used to relieve spasmodic pain in the gut, especially in IBS. Although herbal formulae and Western drugs are commonly coadministered for various diseases in Korea, few clinical studies have been conducted regarding the synergic effects of these treatments for any disease, including D-IBS. METHODS AND ANALYSIS: This trial is a randomised, double-blinded, placebo-controlled, double-dummy, four-arm, parallel study. After a 2-week preparation period, 80 patients with D-IBS will be randomly assigned to one of four treatment groups consisting of SRS (water extract granules, 5 g/pack, three times a day) with OB (tablet form, one capsule three times a day) or their placebos, with treatment lasting for 8 weeks. Post-treatment follow-up will be conducted 4 weeks after the end of treatment. The primary outcome is the finding obtained using the Subject's Global Assessment of Relief method. The secondary outcomes are the severity of symptoms related to D-IBS, determined using a 10-point scale, and the change in symptoms. ETHICS AND DISSEMINATION: This trial has full ethical approval of the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS15MISV0033) and the Korean Ministry of Food and Drug Safety (30769). The results of the study will be disseminated through a peer-reviewed journal and/or conference presentations. TRIAL PROTOCOL VERSION: IS15MISV0033 version 4.0 (25 July 2016). TRIAL REGISTRATION NUMBER: KCT0001621 (approval date: 10 August 2015).

Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis.

Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer, arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of OD, which was investigated both in vitro and chemically, induced HCC model. OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days after confirmed HCC model through 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) imaging. The survival in OD treated groups was shown to have a greater therapeutic effect than the control group. 28 days after OD treatment, OD treated groups resulted in a significant reduction in tumor number, size, (18)F-FDG uptake, and serum levels such as alanine transaminase, aspartate transaminase, and alkaline phosphate compared to the control group. Also, proliferated cells in tumor sites by OD were reduced compared to the control group. Furthermore, several rats in OD treated group survived over 60 days and liver morphology of these rats showed the difference between tumor mass and normal tissue. These results suggest that OD may have antiproliferative activity, inhibition of metastasis, and apoptotic effects in chemically induced HCC model and can have the potential use for clinical application as anticancer drug of the herbal extract.

A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain.

In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo). Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1ß, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1ß, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent.

Therapeutic Effects of Acupuncture through Enhancement of Functional Angiogenesis and Granulogenesis in Rat Wound Healing.

Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.

Changes in brain FDG metabolism induced by acupuncture in healthy volunteers.

BACKGROUND: With the aid of newly developed functional brain imaging studies, studies are ongoing to see if acupuncture first acts on specific brain areas to induce effects on the human body. PURPOSE: To examine if stimulation at specific acupuncture points changes brain glucose metabolism patterns, including the limbic system and specific brain areas related to the acupuncture effect in healthy volunteers using fluorodeoxyglucose positron emission tomography combined computed tomography (FDG-PET/CT). MATERIAL AND METHODS: Twenty healthy volunteers (11 men and 9 women; mean age 49.1+/-7.3 years, age range 35-62 years) were included. Two sets of PET/CT scans were obtained from each volunteer, with and without stimulation by acupuncture. Two classic acupoints, LR3 (liver meridian) and ST44 (stomach meridian) were tested at the same time, using disposable sterile stainless steel needles. After initial acupuncture, the needle was kept in place without further stimulation. FDG-PET/CT scan of the brain began 45 min after FDG injection (185-222 MBq). RESULTS: After stimulation of LR3 and ST44 by acupuncture, glucose metabolism in the brain was increased in the left insula (BA 13), bilateral thalami, superior frontal region of the right frontal lobe, and the inferior frontal region of left frontal lobe compared with baseline. On the other hand, glucose metabolism was decreased after acupuncture in the cingulate and parahippocampal (BA 36) regions of the left limbic lobe. CONCLUSION: Changes of glucose metabolism in specific brain areas following stimulation by acupuncture on LR3 and ST44 were documented using FDG-PET/CT.

Effect of combination therapy with sodium ozagrel and panax ginseng on transient cerebral ischemia model in rats.

Sodium ozagrel (SO) prevents platelet aggregation and vasoconstriction in the cerebral ischemia. It plays an important role in the prevention of brain damage induced by cerebral ischemia/reperfusion. Recently, many animal studies have suggested that the Panax ginseng (PG) has neuroprotective effects in the ischemic brain. In this study, we assessed the neuroprotective effects that come from a combination therapy of SO and PG in rat models with middle cerebral artery occlusion (MCAO). Animals with MCAO were assigned randomly to one of the following four groups: (1) control (Con) group, (2) SO group (3 mg/kg, intravenously), (3) PG group (200 mg/kg, oral feeding), and (4) SO + PG group. The rats were subjected to a neurobehavior test including adhesive removal test and rotarod test at 1, 3, 7, 10, and 15 days after MCAO. The cerebral ischemic volume was quantified by Metamorph imaging software after 2-3-5-triphenyltetrazolium (TTC) staining. The neuronal cell survival and astrocytes expansion were assessed by immunohistofluorescence staining. In the adhesive removal test, the rats of PG or SO + PG group showed significantly better performance than those of the control group (Con: 88.1 ± 24.8, PG: 43.6 ± 11, SO + PG: 11.8 ± 7, P < .05). Notably, the combination therapy group (SO + PG) showed better performance than the SO group alone (SO: 56 ± 12, SO + PG: 11.8 ± 7, P < .05). In TTC staining for infarct volume, cerebral ischemic areas were also significantly reduced in the PG group and SO + PG group (Con: 219 ± 32, PG: 117 ± 8, SO + PG: 99 ± 11, P < .05). Immunohistofluorescence staining results showed that the group which received SO + PG group therapy had neuron cells in the normal range. They also had a low number of astrocytes and apoptotic cells compared with the control or SO group in the peri-infarction area. During astrocytes staining, compared to the SO + PG group, the PG group showed only minor differences in the number of NeuN-positive cells and quantitative analysis of infarct volume. In conclusion, these studies showed that in MCAO rat models, the combination therapy with SO and PG may provide better neuroprotective effects such as higher neuronal cell survival and inhibition of astrocytes expansion than monotherapy with SO alone.