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Delirium is defined as a state that patient is in acute disturbance of consciousness with decreased ability to focus, maintain, or attention, accompanied by cognition change and perceptual disturbances. Postoperative delirium (POD) is a form of delirium, characterized in patients who have undergone surgical procedure and newly diagnosed with a delirium after surgical procedure and anesthesia. There is no definite mechanism how POD happens, but some possible causes are known : inflammation, neurotransmitter, chronic stress, metabolic disorders, electrolyte disorders and sleep-wake disturbance. Though incidence of POD is about 5%-15%, POD is still under-recognised among health care provider. And POD often fatal for patients. It can leads to increasing health care cost, making poor prognosis after surgery and lengthening hospital stay. Acupuncture is defined as an intervention stimulated specific points using needles with various manipulations. Acupuncture is widely used in managing pain recently but also used for mental problems like an anxiety, insomnia, anxiety, depression, dementia, cognitive impairment, and delirium. For producing sedation without complications, acupuncture could be a potential intervention for POD. There are several clinical trials that acupuncture is effective for POD. However, there is no systematic reviews of acupuncture on this condition. Therefore, the aim of this review is to draw a definitive conclusion on acupuncture for POD.

Melasma is a common hypermelanosis that occurs in areas exposed to sunlight, especially the face. It occurs rarely before puberty and is commonly observed in women, especially women of childbearing age. It is also observed in 10% of men. New melasma often arises and existing melasma may worsen during pregnancy. Symptoms appear as brown macules with irregular borders and occur symmetrically in the photodistribution of sunlight on the face. They are often fused in a reticular pattern. They are darkened by sunlight, which makes them worse during summer and improves during winter, i.e., there is a seasonal change. Melasma is common among Asian and Hispanic women who live in areas with strong sunlight. It occurs frequently in patients with Fitzpatrick skin types IV, V, and VI [1].

Although there are many side effects that can occur after laser treatment, the most common and problematic side effect in darker skin including Koreans is postinflammatory hyperpigmentation (PIH). Therefore, a full understanding and management of PIH are necessary. In this chapter, we go through PIH in detail.

Many papers and dermatology laser texts usually describe lasers about white skin. In separate articles or chapters laser treatment of “darker skin” or ethnic, nonwhite, pigmented skin is described [1–4]. Here, the term “darker skin” refers to all races except Caucasians, including Chinese, Japanese, Indian, Pakistani, Hispanic, Latino, African, African-Caribbean, and African American. Fitzpatrick skin types are III, IV, V, and VI [5].

Skin rejuvenation is a treatment that targets age-related pigmentation disorders and telangiectasia or improves wrinkles and skin texture [1]. It can be classified by treatment methods; ablative rejuvenation (AR) by CO2 laser and erbium-doped yttrium aluminium garnet (Er:YAG) laser or nonablative rejuvenation (NAR), which induces a selective thermal reaction to the dermis and subcutaneous fat while sparing the epidermis. It can also be classified by treatment targets; type I rejuvenation targets pigmentation and vascular disorders while type II rejuvenation focuses on improving wrinkles and skin texture. For example, AR and NAR are both treatment modalities for type II rejuvenation (Table 9.1). Generally, NAR refers to rejuvenation treatment that uses nonablative methods to improve wrinkles and skin texture (type II rejuvenation).

Background/Aims: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. Methods: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. Results: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27-96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. Conclusions: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection. (Clin Mol Hepatol 2018;24:311-318)

Background This study aims to assess the efficacy and safety of geonchildan, a Korean traditional herbal medicine, for patients with active rheumatoid arthritis (RA) and evaluate the feasibility of a large-scale confirmatory clinical trial. Methods/design This is a randomized, double-blind, placebo-controlled, parallel two-arm pilot trial in Seoul, Korea. Altogether, 30 patients diagnosed with RA for at least 3 months and with a Disease Activity Score for 28 joints (DAS28) ≥ 3.2 will be enrolled. Participants are randomly assigned to one of two groups, the experimental group or the placebo group, in a 1:1 ratio and will make four scheduled visits. The participants will be administered geonchildan or a placebo three times per day for 12 weeks. The change in DAS28 will be examined as the primary efficacy outcome. The secondary efficacy outcomes include the proportion of patients achieving ACR20, ACR50, ACR70, and EULAR responses; the DAS28 sub-items; the consumption of medication; Korean Health Assessment Questionnaire scores; inflammatory parameters; and the Korean medical diagnostic pattern indicator. Adverse events and laboratory test results will be recorded to evaluate safety. The process, resources used, and management of the study will also be assessed to determine the feasibility of a large-scale trial. Discussion This is the first clinical trial to explore the efficacy and safety of geonchildan in patients with active RA. If the superiority of geonchildan versus the placebo is demonstrated and the study design is feasible, this study could form the foundation for a large-scale clinical trial. The results will be published in a peer-reviewed journal. Trial registration Clinical Research Information Service, KCT0001943. Registered on 14 June 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2849-3) contains supplementary material, which is available to authorized users.

Herbal medicines have been used as a treatment option for rheumatic disease (RD), but they often produce liver enzyme abnormality. This study examines the incidence of herb-induced liver injury (HILI) and the relationship between risk factors and liver enzyme abnormality (LEA) in inpatients with RD. HILI was analyzed using the Roussel Uclaf causality assessment method liver injury criteria and causality assessment. Multivariable analysis was performed to assess the relationship between patient characteristics and LEA in RD. The features of LEA were also examined in each RD. Among 352 patients included in this study, 105 patients showed LEA on admission, of which 6 had fulfilled the Roussel Uclaf causality assessment method criteria. The incidence risks of LEA and HILI were 12.55% and 0.58%, respectively. Multivariable analysis showed that LEA on admission and occasional use of alcohol could be risk factors for LEA on follow-up. In an additional analysis with each RD, all rheumatoid arthritis patients with LEA were taking nonsteroidal anti-inflammatory drugs, steroids, and disease-modifying antirheumatic drugs, and 4 out of 5 gout patients with LEA were taking steroids. The use of herbal medicine in RD is relatively safe. However, regular monitoring of liver enzyme tests and examination of alcohol consumption are required.

Background: This study aims to evaluate the efficacy, safety, and appropriate dose of Hanslim, a Korean traditional herbal medicine, for obese patients, when compared to a placebo. Methods/design: This study is a randomized, double-blinded, multicenter, multidose, placebo-controlled, phase IIb clinical trial. A total of 165 obese patients with a body mass index (BMI) of more than 30 kg/m2 or obese patients with a BMI of 27 to 29.9 kg/m2 and one or more risk factors such as hypertension, diabetes, or hyperlipidemia will be enrolled. Participants will be randomly assigned to 1 of 3 groups (high-dose, low-dose, or placebo) with a 1:1:1 allocation ratio and will have 4 scheduled visits during the 12-week treatment period. The participants will be administered 2 tablets of Hanslim or placebo, 2 times per day. The difference in the proportion of participants who lost weight by more than 5% from their baseline at 12 weeks compared to the placebo group will be examined as the primary efficacy outcome. Secondary efficacy outcomes include differences in body weight, BMI, body-fat percentage, fat mass, skeletal-muscle mass, edema index, waist circumference, hip circumference, waist-hip ratio, serum lipid, blood glucose, C-reactive protein, and total score of Korean version of obesity-related quality of life after 12 weeks of treatment. Adverse events, laboratory test results, vital sings, and electrocardiography will be recorded to evaluate safety. Discussion: This is the first prospective clinical trial to explore the efficacy and safety of Hanslim for obese patients. If the results provide the appropriate dosage of Hanslim, this study would contribute to the confirmatory evidence for the use of Hanslim as a treatment for obesity needed to conduct a large-scale, phase III clinical trial. The results will be published in a peer-reviewed journal. Trial registration: Clinical Research Information Service, ID: KCT0002193. Registered on January 6, 2017. https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7468

Background Osteoporosis is becoming more prevalent in aging societies worldwide, and the economic burden attributable to osteoporotic fractures is substantial. The medications presently available to treat osteoporosis have side effects, and the development of safer and more effective treatments is urgently needed. The aim of this study is to evaluate the efficacy and safety of BHH10, a traditional Korean herbal medicine, in the treatment of postmenopausal osteoporosis. Methods/Design This is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial and will include 168 postmenopausal women aged 55 years and older with osteoporosis. The participants will be recruited competitively from two sites of the Acupuncture and Moxibustion Department of Kyung Hee University Hospital of Korean Medicine, either Hoegidong or Gangdong in Seoul, Korea. Participants will be assigned randomly to one of two groups, the BHH10 group or the placebo group, in a 1:1 ratio, and will have five scheduled visits. Participants will take two tablets of BHH10 or placebo three times daily for 12 weeks. The primary efficacy outcome is the change in bone mineral density at the lumbar spine (L1–4) between baseline (visit 1) and 12 weeks after randomization (visit 5). Other outcome variables include changes in bone turnover markers, the Deficiency Syndrome of the Kidney Index, EuroQol five-dimension questionnaire score, and laboratory parameters, as well as adverse events. Discussion To our knowledge, this will be the first clinical trial to assess the efficacy and safety of BHH10 in postmenopausal women with osteoporosis. It is anticipated that the results will contribute to the development of traditional herbal medicines that can be used to treat osteoporosis in postmenopausal women in Korea. If the superiority of BHH10 over placebo is demonstrated, this study could provide the foundation for a phase III clinical trial. The results of the study will be published in a peer-reviewed journal. Trial registration Clinical Research Information Service, KCT0001842. Registered on 14 March 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2854-6) contains supplementary material, which is available to authorized users.

OBJECTIVE A retrospective chart review was conducted to explore the effect of Gambisan, a granular extract of novel herbal medicine, for short-term (≤16 weeks) weight loss in adults who are overweight and those with obesity. METHODS Outpatients of Kyung Hee University Korean Medicine Hospital (Seoul, Korea) who took Gambisan and underwent bioelectric impedance analysis were selected (Jan 2011 to Dec 2015); their electronic medical records and clinical charts were retrospectively reviewed. The effectiveness of Gambisan was primarily evaluated by comparing body weight (BW) at baseline and endpoint, using paired t tests; the safety of Gambisan was evaluated on the basis of adverse events (AEs) experienced by patients. RESULTS Two hundred five patients were included in this study. The study population exhibited a significant reduction in BW (73.69 ± 14.49 kg to 69.01 ± 13.20 kg, P

Objectives : The aim of this study is to evaluate the safety of acupuncture therapy when applied to patients who are undergoing anticoagulants / antiplatelet medication therapy combined with herbal medicine using a retrospective, case-control study. Methods : 428 charts of patients were reviewed in this study. Odds ratio between case of bleeding-related adverse event and control was calculated as main analysis. Exposures were anticoagulants / antiplatelet medication, Hwalhyeolgeoeo herbal medicine and combination of both drugs. Additionally, odds ratios were calculated according to the severity of bleedingrelated adverse events. Results : The results were as following: 1. Analysis of all bleeding-related adverse events showed there was no increased risk of combined therapy compared with other exposures and control group. 2. Analysis of only clinically significant adverse events showed there was no increased risk of combined therapy compared with other exposure and control group. 3. Hwalhyeolgeoeo herbal medicine group showed a tendency of increased risk of bleedingrelated adverse events in all analysis but was not statistically significant. Conclusions : The results suggest that Hwalhyeolgeoeo herbal medicine-anticoagulant / antiplatelet medication combined therapy may not increase risk of bleeding-related adverse events in acupuncture therapy. By executing various modules of analysis, it was possible to acquire useful data for possible future studies. Further research is needed to confirm such results.

Jasin-hwan-gagambang (BHH10), a modified prescription of Jasin-hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)-induced rats. Sprague–Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17β-estradiol (E2). BHH10 treatment significantly inhibited OVX-induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C-telopeptide type 1 collagen, and bone morphogenetic protein-2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10-treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN-treated or E2-treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.

Objectives : The purpose of this study was to evaluate the efficacy of HT008 on pain relief and functional improvement in participants with mild knee osteoarthritis (OA) in comparison with that of glucosamine sulfate. Methods : This randomized double-blind trial was conducted at Kyung Hee University Medical Center in Seoul where participants with knee pain for more than 6 months and degenerative osteoarthritis were enrolled. The 100 participants were received either HT008 or glucosamine sulfate 750 mg twice daily for 8 weeks and evaluated at baseline, 4 and 8 weeks after the treatment. We primarily evaluated the differences between two groups with respect to changes in the visual analogue score (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 8. Secondarily the difference between and within two groups with respect to changes in WOMAC stiffness and physical function score, and Lequesne Functional Severity Index (LFI) were also evaluated. Results : At week 8, treatment with HT008 resulted in a significant reduction of the VAS for pain and WOMAC pain scores compared to the glucosamine sulfate (both p

The study objectives were to establish ojeok-san (Five Accumulation Powder: wu ji san) administration criteria and a questionnaire to evaluate the holistic effects of ojeok-san on patients with low back pain (LBP).Texts and literatures, recommended by specialists, were searched to gather ojeok-san-related symptoms. Then, the opinions of Oriental medicine doctors (OMDs) practicing in Seoul were surveyed to ask which symptoms they consider the most in clinical practice. Based on the survey, selection of potential items for the questionnaire was made. The final version was established based on the results of the survey and Delphi process of musculoskeletal diseases specialists. In order to evaluate the reliability and validity of the newly developed assessment tool (Ojeok-san Low Back Questionnaire: OLQ), patients with chronic LBP were recruited. OLQ and other tools such as visual analogue scale, numeric rating scale, Roland-Morris Disability Questionnaire, Modified-Modified Schober test, and 36-Item Short Form Health Survey were applied to the subjects in a 2-week interval. Test-retest reliability, internal consistency, and convergent and discrimination validity were assessed.A total of 90 potential items were generated by the research team. One hundred and two (102) OMDs fully replied to the survey. Based on the survey results, 34 items were initially selected as potential items. Through Delphi method of experts, 10 top items, rated more than 5 points on a scale of 10, were finally established. The 10 items were each established as a response scale of 0-10 (0 as no symptom and 10 as the most excessive form of symptom). Based on the above stages, an initial OLQ was established and used in the evaluation phase. The validity and reliability of OLQ assessment results showed high test-retest reliability, intraclass correlation coefficient, and internal consistency.The newly developed Ojeok-san administration criteria and questionnaire may be a promising tool for future Oriental medicine clinical study protocols.

Objectives : The aim of this study was to observe the effect of balanced acupuncture on herniated intervertebral disc of lumbar spine patients. Methods : We investigated 23 cases of in-patients with acute & subacute herniated intervertebral disc of lumbar spine in oriental hospital, and divided patients into two groups. We treated one group(12 people) by complex oriental medical treatment with Balanced acupuncture, and the other group(11 people) by complex oriental medical treatment without Balanced acupuncture. To evaluate the effectiveness of treatment applied for two groups, we used visual analog scale(VAS) and rating scale for low back pain at admission and discharge. Results : 1. In balanced acupuncture group and control group, compared with baseline and final. VAS was significantly improved. 2. In Balanced acupuncture group and control group, compared with baseline and final. Rating scale for low back pain was significantly improved. 3. VAS and rating scale for low back pain improvement rate in balanced acupuncture group were no statistical significance compared with control group. Conclusions : Balanced acupuncture might be used for relieving symptoms related with herniated intervertebral disc of lumbar spine, but it's no statistical significance.

Objectives : The aim of this study was to investigate whether warm-needling is more effective than acupuncture in relieving the pain and improving the symptoms of knee osteoarthritis(OA). Methods : 76 volunteers with knee OA participated in the study. The subjects were randomly assigned to one of two groups. One group received warm-needling(n=38), while the other group received acupuncture(n=38). Sixteen sessions of warm-needling or acupuncture were conducted on the pain region of each problematic knee over a period of 8 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) scores, physical health score based on the 36-Item Short-Form Health Survey(SF-36) and the Global Assessment(PGA) was measured. Results : Compared to the acupuncture group, the warm-needling group showed a significant decrease in pain, function, and total WOMAC scores according to the Mann-Whitney U-test. The PGA scores of the warm-needling group also showed a significant improvement compared to the acupuncture group. Conclusions : Warm-needling showed a greater pain relief effect on knee OA compared to the acupuncture group. These findings suggest that warm-needling may be a promising alternative therapy for treating knee OA.

We investigated the effect of galangin, a natural flavonoid, on osteoclastic bone destruction in collagen-induced arthritis and examined the molecular mechanisms by which galangin affects osteoclastogenesis in bone marrow derived macrophages. In mice with collagen-induced arthritis, administration of galangin significantly reduced the arthritis clinical score, edema and severity of disease without toxicity. Interestingly, galangin treatment during a later stage of collagen-induced arthritis, using mice with a higher clinical arthritis score, still significantly slowed the progression of the disease. Extensive cartilage and bone erosive changes as well as synovial inflammation, synovial hyperplasia and pannus formation were dramatically inhibited in arthritic mice treated with galangin. Furthermore, galangin-treated arthritic mice showed a significant reduction in the concentrations of IL-1β, TNF-α and IL-17. We found that galangin inhibited osteoclastogenic factors and osteoclast formation in bone marrow-derived macrophages and osteoblast co-cultured cells, and increased osteoprotegerin (OPG) levels in osteoblasts. Galangin and NF-κB siRNA suppressed RANKL-induced phosphorylation of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Also, the JNK inhibitor SP600125 and p38 inhibitor SB203580 reduced RANKL-induced expressions of phospho-c-Jun, c-fos and NFATc1 genes during osteoclast development. In addition, galangin suppressed RANKL-induced phosphorylation of NF-κB, phospho-IκBα, inflammatory cytokines and osteoclast formation in bone marrow-derived macrophages. Our data suggest that galangin prevented osteoclastic bone destruction and osteoclastogenesis in osteoclast precursors as well as in collagen-induced arthritis mice without toxicity via attenuation of RANKL-induced activation of JNK, p38 and NF-κB pathways.

Melittin (1) is a major polypeptide in honey bee venom that has been used traditionally against chronic inflammation and cancer. However, its molecular mechanism has not been determined. In this study, the antitumor effect of 1 was compared with that of NS398, a cyclooxygenase-2 (COX-2) inhibitor, in vivo and in vitro. Subcutaneous injection of 1 at 0.5 and 5 mg/kg suppressed significantly vascular endothelial growth factor (VEGF)-A-transfected highly metastatic Lewis lung cancer (VEGF-A-hm LLC) tumor growth by 25% and 57%, respectively. Also, 1 inhibited significantly the number of vessels around VEGF-A-hm LLC cells. The results were superior to those obtained in the mice treated with NS398. Compound 1 dose-dependently inhibited proliferation and tube formation in human umbilical vein endothelial cells (VEGF-A-HUVECs), without affecting cell viability in native HUVECs. In addition, 1 decreased the expression of VEGF receptor-2 (VEGFR-2), COX-2, and prostaglandin E2 (PGE2) in VEGF-A-transfected HUVECs. These effects were accompanied by a reduction of the phosphorylation of extracellular signal-regulated kinase 1/2 and c-jun N-terminal kinase, whereas it increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK). SB203580 abolished the downregulation of COX-2 and VEGFR-2 and the inhibition of cell proliferation by 1. The antitumor activity of 1 may be associated with antiangiogenic actions via inhibiting VEGFR-2 and inflammatory mediators involved in the MAPK signaling pathway.

Background People living with chronic kidney disease (CKD) experience a range of symptoms and often have complex comorbidities. Many pharmacological interventions for people with CKD have known risks of adverse events. Acupuncture is widely used for symptom management in patients with chronic diseases and in other palliative care settings. However, the safety and efficacy of acupuncture for people with CKD remains largely unknown. Objectives We aimed to evaluate the benefits and harms of acupuncture, electro-acupuncture, acupressure, moxibustion and other acupuncture-related interventions (alone or combined with other acupuncture-related interventions) for symptoms of CKD. In particular, we planned to compare acupuncture and related interventions with conventional medicine, active non-pharmacological interventions, and routine care for symptoms of CKD. Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 28 January 2016 through contact with the Information Specialist using search terms relevant to this review. We also searched Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, the National Assembly Library) and Chinese databases (including the China Academic Journal). Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that investigated the effects of acupuncture and related point-stimulation interventions with or without needle penetration that involved six sessions or more in adults with CKD stage 3 to 5, regardless of the language and type of publication. We excluded studies that used herbal medicine or co-interventions administered unequally among the study groups. Data collection and analysis Two authors independently extracted data and assessed risk of bias. We calculated the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes were changes in pain and depression, and occurrence of serious of adverse events. Main results We included 24 studies that involved a total of 1787 participants. Studies reported on various types of acupuncture and related interventions including manual acupuncture and acupressure, ear acupressure, transcutaneous electrical acupuncture point stimulation, far-infrared radiation on acupuncture points and indirect moxibustion. CKD stages included pre-dialysis stage 3 or 4 and end-stage kidney disease on either haemodialysis or peritoneal dialysis. None of the included studies assessed pain outcomes, nor formally addressed occurrence of serious adverse events, although three studies reported three participant deaths and three hospitalisations as reasons for attrition. Three studies reported minor acupuncture-related harms; the remainder did not report if those events occurred. All studies were assessed at high or unclear risk of bias in terms of allocation concealment. Seventeen studies reported outcomes measured for only two months. There was very low quality of evidence that compared with routine care, manual acupressure reduced scores of the Beck Depression Inventory score (scale from 0 to 63) (3 studies, 128 participants: MD -4.29, 95% CI -7.48 to -1.11, I2 = 0%), the revised Piper Fatigue Scale (scale from 0 to 10) (3 studies, 128 participants: MD -1.19, 95% CI -1.77 to -0.60, I2 = 0%), and the Pittsburgh Sleep Quality Index (scale from 0 to 21) (4 studies, 180 participants: MD -2.46, 95% CI -4.23 to -0.69, I2 = 50%). We were unable to perform further meta-analyses because of the paucity of data and problems with clinical heterogeneity, such as different interventions, comparisons and timing of outcome measurements. Authors' conclusions There was very low quality of evidence of the short-term effects of manual acupressure as an adjuvant intervention for fatigue, depression, sleep disturbance and uraemic pruritus in patients undergoing regular haemodialysis. The paucity of evidence indicates that there is little evidence of the effects of other types of acupuncture for other outcomes, including pain, in patients with other stages of CKD. Overall high or unclear risk of bias distorts the validity of the reported benefit of acupuncture and makes the estimated effects uncertain. The incomplete reporting of acupuncture-related harm does not permit us to assess the safety of acupuncture and related interventions. Future studies should investigate the effects and safety of acupuncture for pain and other common symptoms in patients with CKD and those undergoing dialysis.

Introduction Whiplash-associated disorder (WAD) is a general after-effect of motor vehicle collisions or sporting accidents. Acupuncture is a common intervention for pain conditions such as musculoskeletal disease. We conducted a pilot trial to determine the efficacy and safety of acupuncture for patients with WAD. Methodology Forty participants were randomly allocated to an acupuncture group or a waiting-list group. The acupuncture group received acupuncture treatment three times per week for 2 weeks. Symptoms were evaluated before random allocation and after 2 weeks. The primary outcome measure was pain intensity. Secondary outcome measures were the SF-36, cervical range of motion (ROM), Self-Rating Depression Scale (SDS), and the Cornell Medical Index (CMI). Results The results demonstrated that the change in visual analogue scale (VAS) in the acupuncture group was −1.85 [−2.67 to −1.02], compared to −0.40 in the waiting-list group [95% CI: −1.18 to 0.38] (p = 0.001). VAS significantly improved from 4.59 [3.67–5.48] at baseline to 2.74 [2.08–3.37] at the endpoint (p Conclusions Acupuncture treatment was associated with a significant alleviation of pain. This pilot study provided preliminary data on the efficacy and safety of acupuncture treatment for WAD. A full-scale randomized controlled trial is required to provide firm evidence of the effectiveness of this intervention.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent Cl?/HCO₃? anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

Bee venom (BV) treatment is the therapeutic application of honeybee venom (HBV) for treating various diseases in Oriental medicine. In the present work, the authors investigated the functional specificity of BV as an angiogenesis inhibitor using in vitro models and in vivo mouse angiogenesis and lung metastasis models. BV significantly inhibited the viability of Lewis lung carcinoma (LLC) cells but did not affect peripheral blood mononuclear lymphocytes (PBML) cells. BV also inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Western blotting analysis showed that BV inhibited AKT and MAPK phosphorylation in LLC cells and HUVECs and down regulated expression of VEGF and VEGFR-2 of LLC cells and HUVECs. Also, BV effectively disrupted VEGF-induced neovascularization in Matrigel plugs in our in vivo angiogenesis assay. When given subcutaneously, BV also significantly suppressed tumor angiogenesis through inhibition of VEGF and VEGFR-2 in LLC model. Mice bearing subcutaneous LLC tumors were treated with 1mug/ml or 10mug/ml of BV. They showed reductions ranging between 49% and 62% in primary tumor volume and reduction of spontaneous pulmonary metastasis occurrences. Furthermore, BV treatment in the spontaneous lung metastases model after primary tumor excision prolonged their median survival time from 27 to 58days. These results suggest that the tumor-specific anti-angiogenic activity of BV takes effect during different stages of tumor progression by blocking the tyrosine phosphorylation of VEGFR-2, and validate the application of BV in lung cancer treatment.

Introduction Thread embedding acupuncture (TEA) is a special type of acupuncture that inserts certain medical threads (eg, catgut or polydioxanone) into subcutaneous tissue or muscles at specific points. Although TEA has been widely used for the treatment of musculoskeletal pain in Korea, China and Taiwan, evidence regarding its efficacy is lacking. The aim of this protocol is to evaluate the effectiveness and safety of TEA in the treatment of musculoskeletal pain, by conducting a systematic review and meta-analysis. Methods and analysis The following 16 databases will be searched from their inception to 14 May 2017: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, three Chinese database (China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database and the Wanfang database) and eight Korean databases (Korean Medical Database, Korean Association of Medical Journal Editors, Korean Studies Information Service System, Korean National Assembly Digital Library, National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, ’Database Periodical Information Academic and Korean Traditional Knowledge Portal9). The WHO International Clinical Trials Registry Platform will also be searched to retrieve the recently completed studies. All randomised controlled studies in which TEA was used on specific points for the treatment of musculoskeletal pain will be included and no restrictions on language will be applied. The risk of bias of each study will be evaluated by the Cochrane risk of bias tool. Mean difference or standardised mean difference for continuous data and risk ratio for dichotomous data will be calculated with 95% CIs using a random effects model or a fixed effects model. Additional subgroup and sensitivity analyses will be conducted according to a predefined protocol. Ethics and dissemination No ethical issues are predicted. The systematic review will be published in a peer-reviewed journal or conference presentation. These findings will summarise the current evidence of TEA for the treatment of musculoskeletal pain and may provide guidance for clinicians and patients to select TEA for musculoskeletal pain. PROSPERO registration number CRD42015019046.

Oriental herbal medicines have been widely used for the prevention or treatment of various diseases including cancer in Asia. However, to prove their chemo preventive efficacies in modern times, scientific evidence for those herbal medicines is required. Thus, in the present study, an effective herbal cocktail Bojungbangdocktang (BJBDT) was investigated to elucidate antiangiogenic mechanism in vitro and in vivo. BJBDT significantly inhibited vascular endothelial growth factor (VEGF) induced proliferation in HUVECs at nontoxic concentrations, despite weak cytotoxicity against human umbilical vein endothelial cells (HUVECs). BJBDT also significantly suppressed VEGF-induced migration and tube formation of HUVECs. Furthermore, BJBDT treatment resulted in pale color and low hemoglobin level in Matrigel plugs, as well as dark red color and high hemoglobin level in untreated control. Interestingly, BJBDT specifically inhibited the binding of VEGF to vascular endothelial growth factor receptor 2 (VEGFR2), but not VEGFR1. In addition, friedelin, formononetin, ginsenoside Rb1, naringin, atractyloside, diosgenin, and allantonin were identified from BJBDT by high-performance liquid chromatography (HPLC) analysis as a quality of control. Taken together, these results suggest that BJBDT is a potent angiogenesis inhibitor blocking the VEGF/VEGFR2 signaling pathway in HUVECs.

The antinociceptive effect and the mechanism of bee venom acupuncture (BVA) on inflammatory pain, especially in the rat model of collagen-induced arthritis (CIA), have not yet been fully studied. This study was designed to investigate the antinociceptive effect and its μ-opioid and α 2 -adrenergic mechanism of BVA in the CIA rat model. To induce CIA, male Sprague–Dawley rats were immunized with bovine type II collagen emulsified in Freund's incomplete adjuvant followed by a booster injection 14 days later. The antinociceptive effect was evaluated by tail flick latency (TFL). After induction of arthritis, the inflammatory pain threshold decreased as time passed, and there was no big change of the pain threshold after 3 weeks. Three weeks after the first immunization, BVA (0.25 mg/kg) injected into the Zusanli acupoint (ST 36 ) showed the antinociceptive effect. Furthermore, the antinociceptive effect of BVA was blocked by yohimbine (α 2 -adrenergic receptor antagonist, 2 mg/kg, i.p) pretreatment, but not by naloxone (μ-opioid receptor antagonist, 2 mg/kg, i.p.) pretreatment. These results suggest that BVA can relieve inflammatory pain in CIA and the antinociceptive effect of BVA can be mediated by α 2 -adrenergic receptor.

Formononetin (1), a plant-derived phytoestrogen, possesses bone protective properties. To address the potential therapeutic efficacy and mechanism of action of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs). Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG) and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly inhibited RANKL-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB siRNA suppressed AKT, ERK, JNK, and p38 MAPK phosphorylation. Furthermore, 1 significantly suppressed c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key transcription factors during osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast formation. These results suggested that 1 acted as an antiresorption agent by blocking osteoclast activation.

Bee venom acupuncture (BVA), as a kind of herbal acupuncture, exerts not only pharmacological actions from the bioactive compounds isolated from bee venom but also a mechanical function from acupuncture stimulation. BVA is growing in popularity, especially in Korea, and is used primarily for pain relief in many kinds of diseases. We aimed to summarize and evaluate the available evidence of BVA for rheumatoid arthritis and osteoarthritis. Computerized literature searches for experimental studies and clinical trials of BVA for arthritis were performed on the databases from PUBMED, EMBASE and the Cochrane Library. In addition, two leading Korean journals (The Journal of Korean Society for Acupuncture and MoxibustionandThe Journal of Korean Oriental Medicine) were searched for relevant studies. The search revealed 67 studies, 15 of which met our criteria. The anti-inflammation and analgesic actions of BVA were proved in various kinds of animal arthritic models. Two randomized controlled trials and three uncontrolled clinical trials showed that BVA was effective in the treatment of arthritis. It is highly likely that the effectiveness of BVA for arthritis is a promising area of future research. However, there is limited evidence demonstrating the efficacy of BVA in arthritis. Rigorous trials with large sample size and adequate design are needed to define the role of BVA for these indications. In addition, studies on the optimal dosage and concentration of BVA are recommended for future trials.

It has been known that acupuncture has various effects such as analgesia, promotion of homeostasis, improvements in brain circulation, and rectification of internal disorders. Neuropeptide Y (NPY), a 36-amino-acid peptide, is known to increase appetite. In the present study, the effect of acupuncture stimulation at Zusanli (St.36) on NPY expression in the Streptozotocin (STZ)-induced diabetic rats was investigated via immunohistochemistry. Increased NPY expression was detected in both the Arcuate nucleus (ARN) and the Paraventricular nucleus (PVN) of the Hypothalamus in rats with in STZ-induced diabetes. Needling on Zusanli resulted in decreased NPY levels in both the ARN and PVN of diabetic rats. The present study shows that acupuncture suppressed NPY expression in the ARN and PVN of the Hypothalamus in STZ-induced diabetic rats, suggesting the possibility that acupuncture treatment is effective in curbing the hyperphagia of diabetes.

AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate (TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response (CVR) and Hepatitis B e antigen (HBeAg) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBeAg seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus (HBV) DNA in both groups, but CVR was higher in the compensated group (88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores in decompensated group (P < 0.001). Of the 57 decompensated patients, 39 (68.4%) achieved CTP class A and 27 (49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/dL increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively (P < 1.000). CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.

Background/Aims: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach. Methods: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization. Results: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern. Conclusions: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future. (Korean J Gastroenterol 2007;49:209-224)

Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1 beta-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1 beta (IL-1 beta). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-beta, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y-box (SRY-box) containing gene 9 (SOX9), type 2 alpha 1 collagen (Col2 alpha 1), cartilage link protein, and aggrecan. In IL-1 beta-stimulated MSCs, mangiferin significantly reversed the production of TGF-beta, BMP-2, BMP-4, SOX9, Col2 alpha 1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1 beta-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2 alpha 1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.

Objectives This study aims to assess the completeness of reporting of randomised controlled trials (RCTs) of acupuncture in the Korean literature. Design Systematic review. Methods We searched 12 Korean databases and 7 Korean journals to identify eligible RCTs of acupuncture published from 1996 to July 2011. We used the Consolidated Standards of Reporting Trials (CONSORT) checklist for parallel RCTs and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) to assess the quality of reporting in Korean RCTs. We compared the completeness of reporting of CONSORT and STRICTA items in RCTs published in two time periods (1996–2004 referred to as the early period and 2005–2011 referred to as the late period). Results We analysed 146 eligible RCTs using the CONSORT statement concerning RCTs of both needling and non-needling acupuncture and the STRICTA guidelines for 90 trials of needling acupuncture. Among the 103 RCTs in the late period, the proportion of RCTs that completely reported the CONSORT items of outcome definition (15.5%), sample size calculation (2.9%), randomisation (56%), allocation concealment (5.8%), implementation of allocation (11.7%), outcome assessor blinding (20.3%), flow of participants (25.2%), number of participants analysed (19.4%), ancillary analyses (0.0%), adverse events (24.3%), generalisability of findings (1.9%) and overall evidence (32.0%) remained small. Among the 61 RCTs of needling acupuncture in the late period, the STRICTA items of setting/context (24.6%) and practitioner background (27.9%) showed incomplete reporting. The completeness of reporting improved over time in several CONSORT and STRICTA items. Conclusions The completeness of reporting of Korean RCTs of acupuncture was suboptimal according to the CONSORT and revised STRICTA statements. Trial authors and journal editors should use the CONSORT statement and STRICTA guidelines for transparent reporting in Korean RCTs of acupuncture. The endorsement of the CONSORT and revised STRICTA statements in author instructions is also required.

Arginine, an alpha-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type I alpha 1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer-binding protein alpha (C/EBP alpha), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway.

Objectives High-quality reporting of treatment details can aid replication of study results in real-world clinical practice. The Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) is a reporting guideline for key elements of acupuncture interventions in clinical trials. This study used STRICTA to investigate whether Cochrane reviews of acupuncture adequately report important treatment details. Design Systematic review Methods Cochrane reviews of acupuncture were identified from The Cochrane Library (issue 7, 2012). Randomised controlled trials (RCTs) included in the reviews and published after 2005 were obtained. Using STRICTA, we extracted acupuncture-related information from the Cochrane reviews and the RCTs. The characteristics of the included studies’ table were the major source of intervention information from Cochrane reviews. Reporting quality of acupuncture interventions in Cochrane reviews was assessed and compared with the respective RCTs. Results 25 Cochrane reviews of acupuncture and 92 RCTs met the selection criteria. Cochrane reviews were 16% less likely to report the acupuncture-related items of STRICTA than RCTs (risk ratio 0.84, 95% CI 0.79 to 0.88, I2=8%). Information was significantly better reported for 10 of the 15 treatment-group items of STRICTA in RCTs than in Cochrane reviews (p

In Oriental Medicine, mononeuropathy belongs to or . Common peroneal neuropathy(CPN) is the most frequently encountered mononeuropathy in the lower extremity. It is usually caused by direct surgery injury, compression, leg crossing, trauma, traction etc, occasionally by nerve tumor. A 47-year-old healthy man was complained of the sudden development of left foot drop and sensory manifestation owing to suspected compression and habitual leg-crossing. Acupuncture along with bee-venom acupuncture, moxibustion was performed mainly at Stomach and Gallbladder Meridian specially ST36, ST37, ST40, GB34 and GB39. Nerve conduction study and electromyography was also performed three times. Symtoms was relieved fast, and full recovery took about 110 days. Acupuncture and bee-venom acupuncture are considered to be beneficial to CPN. More clinical trials and studies are needed.

Hemiplegic shoulder pain(HSP) is one of the most frequent and difficult problems affecting poststroke hemiplegic patients. Honeybee venom acupuncture therapy(BVAT) is known for its pain relieving effects in arthralgia. To evaluate the effectiveness of BVAT on HSP, 24 patients were sequential1y allocated into BVA T treatment group and control group and monitored for 4 weeks at time interval of initial(T0), 1 week(T1), 2 weeks(T2) and 4 weeks(T4). In treatment group, 1:10000 honeybee venom solution 0.2㎖ was injected into acupoint(s) following Deqi three times a week. Kyonu(LI15) was used in the first week. Thereafter Kyonu(LI15) and Nosu(SI10) were used. Visual analogue scale of pain severity showed significant decrease in treatment group compared to control group at T2 and T4 evaluation. Painless passive range of motion of shoulder external rotation showed significant increase in treatment group compared to control group at T4 evaluation. Fugl-Meyer Motor Assessment of upper limb motor function and Modified Ashworth scale of the spasticity of upper limb showed no difference between two groups. BVAT showed as an effective therapy in HSP and further extensive clinical studies are expected.

In order to study Bee venom and Pain, We searched Journals and Internet. The results were as follows: 1. The domestic papers were total 13. 4 papers were published at The journal of korean acupuncture & moxibustion society, 3 papers were published at The journal of korean oriental medical society, Each The journal of KyoungHee University Oriental Medicine and The journal of korean sports oriental medical society published 1 papers and Unpublished desertations were 3. The clinical studies were 4 and the experimental studies were 9. 2. The domestic clinical studies reported that Bee venom Herbal Acupuncture therapy was effective on HIVD, Subacute arthritis of Knee Joint and Sequale of sprain. In the domestic experimental studies, 5 were related to analgesic effect of Bee vnom and 4 were related to mechanism of analgesia. 3. The journals searched by PubMed were total 18. 5 papers were published at Pain, Each 2 papers were published at Neurosci Lett. and Br J Pharmacol, and Each Eur J Pain, J Rheumatol, Brain Res, Neuroscience, Nature and Toxicon et al published 1 paper. 4. In the journals searched by PubMed, Only the experimental studies were existed. 8 papers used Bee Venom as pain induction substance and 1 paper was related to analgesic effects of Bee venom. 5. 15 webpage were searched by internet related to Bee Venom and pain. 11 were the introduction related to arthritis, 1 was the advertisement, 1 was the patient's experience, 1 was the case report on RA, 1 was review article.

AIM: To investigate anxiety and depression propensities in patients with toxic liver injury. METHODS: The subjects were divided into three groups: a healthy control group (Group 1, n = 125), an acute non-toxic liver injury group (Group 2, n = 124), and a group with acute toxic liver injury group caused by non-commercial herbal preparations (Group 3, n = 126). These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale (HADS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and the hypochondriasis scale. RESULTS: The HADS anxiety subscale was 4.9 ± 2.7, 5.0 ± 3.0 and 5.6 ± 3.4, in Groups 1, 2, and 3, respectively. The HADS depression subscale in Group 3 showed the most significant score (5.2 ± 3.2, 6.4 ± 3.4 and 7.2 ± 3.4 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). The BAI and BDI in Group 3 showed the most significant score (7.0 ± 6.3 and 6.9 ± 6.9, 9.5 ± 8.6 and 8.8 ± 7.3, 10.7 ± 7.2 and 11.6 ± 8.5 in Groups 1, 2, and 3, respectively) (BAI: P < 0.01 vs Group 1, P < 0.05 vs Group 2) (BDI: P < 0.01 vs Group 1 and 2). Group 3 showed a significantly higher hypochondriasis score (8.2 ± 6.0, 11.6 ± 7.5 and 13.1 ± 6.5 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). CONCLUSION: Psychological factors that present vulnerability to the temptation to use alternative medicines, such as herbs and plant preparations, are important for understanding toxic liver injury.

Among cancer patients, cancer-related fatigue (CRF) is one of the most common symptoms and adversely affects physical ability and quality of life even several years after treatment. This study aims to evaluate the current evidence for moxibustion in patients with CRF. Eighteen databases were searched from their inception to April 2013. All randomized controlled trials (RCTs) of moxibustion for treating CRF without language restriction were considered for inclusion. The risk of bias and reporting quality of each study were assessed using the Cochrane risk of bias tool, Consolidated Standards of Reporting Trials (CONSORT), and Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Risk ratio (RR) or mean difference (MD) was used to measure the treatment effect with 95 % confidence intervals (CIs) in a random effects model. Four RCTs with a total of 374 subjects were included for the review. These four studies compared moxibustion plus routine care with routine care alone. Most studies were determined to have a moderate to high risk of bias with low reporting quality. An indirect moxa stick was used in two studies, an indirect ginger cake-separated moxa was used in one study, and in one remaining study, both moxibustion methods were used. Meta-analysis showed the favorable effects of moxibustion on the response rate (RR, 1.73; 95 % CI, 1.29 to 2.32; p = .0003; heterogeneity, I 2 = 15 %, p = .32). Burning with a mild blister after moxibustion was reported in one study. Because of a high risk of bias and low reporting quality of the studies included in this review, it is difficult to draw the conclusion that moxibustion is an effective and safe treatment for patients with CRF. Further rigorous research will be necessary to evaluate whether moxibustion has beneficial effects on CRF. PROSPERO. Unique identifier: CRD42013004501.

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecanin vivoand was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagenin vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type IIα1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

Objective Incomplete recovery from facial palsy has a long-term impact on the quality of life, and medical options for the sequelae of Bell's palsy are limited. Invasive treatments and physiotherapy have been employed to relieve symptoms, but there is limited clinical evidence for their effectiveness. Acupuncture is widely used on Bell's palsy patients in East Asia, but there is insufficient evidence for its effectiveness on Bell's palsy sequelae. The objective is to evaluate the efficacy and safety of acupuncture in patients with sequelae of Bell's palsy. Method/Design This study consists of a randomized controlled trial with two parallel arms: an acupuncture group and a waitlist group. The acupuncture group will receive acupuncture treatment three times per week for a total of 24 sessions over 8 weeks. Participants in the waitlist group will not receive any acupuncture treatments during this 8 week period, but they will participate in the evaluations of symptoms at the start of the study, at 5 weeks and at 8 weeks after randomization, at which point the same treatment as the acupuncture group will be provided. The primary outcome will be analyzed by the change in the Facial Disability Index (FDI) from baseline to week eight. The secondary outcome measures will include FDI from baseline to week five, House-Brackmann Grade, lip mobility, and stiffness scales. Trial registration Current Controlled-Trials ISRCTN43104115; registration date: 06 July 2010; the date of the first patient's randomization: 04 August 2010

Ethnopharmacological relevance Traditional medicine has been widely using Phellodendron amurense Rupr. (Rutaceae) to treat various inflammatory diseases including arthritis. Aim of the study This study investigated the effects of Phellodendron amurense in protecting cartilage, including regulating the levels of aggrecanases, matrix metalloproteinases (MMPs)/tissue inhibitor of metalloproteinase (TIMP), proinflammatory cytokines and signaling of the mitogen activated protein kinase (MAPK) pathway in human osteoarticular cartilage and chondrocytes. Materials and methods Explants from human osteoarthritis cartilage were cultured alone or in IL-1α for 7 days with or without Phellodendron amurense ethanol extract or celecoxib (40, 100, 200 μg/ml). The effect of Phellodendron amurense on matrix degradation induced by IL-1α in human articular cartilage was assessed by staining, and the quantities of sulfated glycosaminoglycan (GAG) and type II collagen were calculated from the culture media. The levels of aggrecanases, MMPs, TIMP, and PGE2 in the culture media were investigated using an enzyme-linked immunosorbent assay (ELISA). In addition, reverse transcription polymerase chain reaction (RT-PCR) evaluated the mRNA expression of aggrecanases, MMPs and TIMP. Furthermore, Western blot analysis was performed to identify the roles that Phellodendron amurense played in the ERK, JNK and p38 signaling pathways. Results Phellodendron amurense showed no evident cytotoxicity on human articular cartilage. Phellodendron amurense significantly inhibited the IL-1α-induced degradation of GAG and type II collagen from human osteoarticular cartilage in a concentration-dependent manner. Celecoxib did not significantly inhibit IL-1α-induced release of GAG and only slightly reduced type II collagen. Phellodendron amurense also dose-dependently decreased the levels of aggrecanase-1 and -2, MMP-1, -3, and -13, whereas it increased TIMP-1 expression in human osteoarticular cartilage. Celecoxib only decreased MMP-1 and MMP-13 levels in human osteoarticular cartilage. In addition, Phellodendron amurense reduced the phosphorylation of extracellular signal regulated kinase (ERK)1/2, Jun NH2-terminal kinase (JNK) and activated phospho-p38 MAPK in a dose-dependent manner in human osteoarthritic chondrocytes. Conclusions Phellodendron amurense inhibited osteoarticular cartilage and chondrocyte destruction by inhibiting proteoglycan release and type II collagen degradation, down-regulating aggrecanases, MMP activities and phospho-ERK1/2, JNK and p38 MAP kinase signaling, and up-regulating TIMP-1 activity. Therefore, our results suggest that Phellodendron amurense is a potential therapeutic agent to protect cartilage against OA progression.

Osteoarthritis is a multifactorial disease characterized by loss of articular cartilage and subchondral plate thickening. Therefore, biochemical analysis of the underlying bone tissue has provided important information for treatment of osteoarthritis. In this study, we determined the potential role of formononetin, a phytoestrogen isolated from Astragalus membranaceus to alter the expression of metabolic markers and cytokine production of human normal osteoblasts (Obs) and osteoarthritis subchondral osteoblasts (OA Obs). Human OA Obs and normal Obs were cultured for 3days, 7days or 14days in the present medium only or were treated with various doses of formononetin. Cells were analyzed for viability by WST-8 assay, alkaline phosphatase (ALP) activity, osteogenic markers (osteocalcin (OCN) and type I collagen (Col I)) and cytokines (interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)). The level of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with normal Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and Col I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal Obs. Interestingly, formononetin markedly increased the expression of VEGF and BMP-2 for 3days of culture and significantly increased OCN and Col I at 14days in human normal Obs. The remodeling effect of formononetin on osteogenic markers and cytokines of inflammatory mediators was more striking in OA Obs as well. Taken together, these results could suggest that formononetin has biphasic positive effects on normal Obs and OA Obs by modifying their biological synthetic capacities.

Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague–Dawley rats. A 20 µg/kg or 200 µg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.

We report four cases of toxic hepatitis that occurred after taking a decoction made by boiling down the root of Dictamnus dasycarpus. The four patients had a median age of 60 years, common symptoms of jaundice and general weakness, and stated that they had not consumed alcohol for at least 5 years. The markers of hepatitis A, B, and C were all negative in the patients. Abdominal ultrasonography revealed common bile ducts with normal diameters. Two of the cases were a mother and daughter, and the other two were sporadic. All of them had consumed a decoction made by boiling down the root of Dictamnus dasycarpus five or six times daily until several days before admission. Dictamnus dasycarpus induced liver injury presenting with a benign course lasting less than 1 month after cessation of the causative agent. We suggest that this natural product can cause acute hepatitis in rural areas. (Korean J Hepatol 2008;14:206-212)

Aim of this study Many cartilage protective agents have been developed from natural products, and they have resulted in the development of treatments for osteoarthritis. In this study, we determined the osteoarthritic efficacy and mechanism of butanol fraction from the bark of Betula platyphylla var. japonica (BFBP) in collagenase-induced rabbit model of osteoarthritis (CIA). Materials and methods The right knees of rabbits were injected intra-articularly with collagenase, and rabbits were orally administrated with distilled water (vehicle), BFBP (50, 100 and 200 mg/kg) or celecoxib (100 mg/kg) once a day for 28 days after the initiation of the CIA. Results Oral administration of BFBP dose-dependently suppressed the stiffness and global histologic score. Proteoglycan intensity was considerably increased in a dose-dependent manner. As well, the mRNA expression of MMP-1, and MMP-3 was decreased. On the contrary, the level of TIMP-1 in the synovial fluids was significantly increased in the BFBP treated group. The pathologic inflammatory molecules such as PGE2 and COX-2 were inhibited by BFBP, but COX-1 expression not affected. Conclusion We suggest that BFBP has shown the protective effect on cartilage alternations through balance of MMPs/TIMP-1 and regulates inflammatory-related molecules in vivo model of osteoarthritis, and great candidate for development of osteoarthritis treatment.