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Kai-Chih Chang,
Ching-Cheng Hsu,
Shing-Hwa Liu,
Chin-Chuan Su,
Cheng-Chieh Yen,
Ming-Jye Lee,
Kuo-Liang Chen, Tsung-Jung Ho,
Dong-Zong Hung,
Chin-Ching Wu,
Tien-Hui Lu,
Yi-Chang Su,
Ya-Wen Chen,
Chun-Fa Huang
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ABSTRACT: Cadmium (Cd), one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have suggested a possible link between Cd exposure and diabetes mellitus (DM). However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP) and the increase of cytosolic cytochrome c release), the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose) polymerase (PARP) cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK)1/2, and p38-mitogen-activated protein kinase (MAPK), which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA) transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580) did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.
PLoS ONE 01/2013; 8(2):e54374. · 4.09 Impact Factor
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Biomedical Engineering Applications Basis and Communications 01/2012; 24(1):17-25. · 0.24 Impact Factor
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ABSTRACT: Excessive endurance exercise training (EEET) is accompanied by cardiac remodeling, changes in ventricular function and increased heart failure risk. Fasudil, a potent Rho-kinase inhibitor, has been demonstrated to blunt cardiomyocyte hypertrophy, cardiac remodeling, and heart failure progression in pre-clinical trials and has been approved for clinical use in Japan. We examined the in vivo bioefficacy of fasudil against EEET-induced cardiac remodeling and the underlying molecular mechanisms. Male Sprague-Dawley rats were randomly divided into three groups: sedentary control (SC), EEET, and EEET with fasudil treatment (EEET-F). Rats in EEET and EEET-F groups ran on a motorized treadmill for 12 weeks. The results revealed that EEET increased myocardial hypertrophy (LV weight/tibial length), myocyte cross-sectional area, hypertrophy-related pathways (IL6/STAT3-MEK5-ERK5, calcineurin-NFATc3, p38 and JNK MAPK), hypertrophic markers (ANP/BNP), pro-apoptotic molecules (cytochrome C, cleaved caspase-3 and PARP), and fibrosis-related pathways (FGF-2-ERK1/2) and fibrosis markers (uPA, MMP-9 and -2). These pathways were then expressed lower in the EEET-F group when compared with the EEET group. The cardiac hypertrophic level, apoptotic pathway and fibrosis signaling were further inhibited in the fasudil-treated group. We systematically investigated the possible signaling pathways leading to EEET-induced cardiac hypertrophy, apoptosis and fibrosis. We also provide evidence for the novel function of fasudil in suppressing EEET-induced cardiac remodeling and impairment by multiple mechanisms, which suggests that the RhoA signaling pathway contributes to EEET-induced cardiac remodeling and dysfunction.
Arbeitsphysiologie 12/2011; 112(8):2943-55. · 2.15 Impact Factor
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Hsi-Chin Wu,
Ching-Yao Yang,
Dong-Zong Hung,
Chin-Chuan Su,
Kuo-Liang Chen,
Cheng-Chieh Yen, Tsung-Jung Ho,
Yi-Chang Su,
Chun-Fa Huang,
Chun-Hung Chen,
Ling-Mei Tsai,
Ya-Wen Chen
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ABSTRACT: Nickel (Ni), a well-known toxic metal, is widely used in electroplating and alloy production. It is also significantly implicated in industrial and environmental pollution caused by uncontrolled industrial and municipal discharges. In this study, we characterized and investigated the cytotoxic effects of Ni exposure and their probable toxicological mechanisms in the pancreatic β-cells. The results showed that it was significantly decreased cell viability after exposing pancreatic β-cell-derived RIN-m5F cells to NiCl(2) for 24h in a dose-dependent manner. NiCl(2) also increased sub-G1 hypodiploid cells and Annexin V-Cy3 binding population in RIN-m5F cells, indicating that it has apoptosis-inducing ability. Moreover, the exposure of RIN-m5F cells to NiCl(2) induced distinct signals of mitochondria-dependent apoptosis, including mitochondrial dysfunction (the disruption of mitochondrial membrane potential (MMP) and increase in mitochondrial cytochrome c release into the cytosol), Bak and Bid mRNA up-regulation, and activation of caspase-3, caspase-7, and caspase-9, and poly(ADP-ribose) polymerase (PARP) degradation. In addition, NiCl(2) also markedly induced the activation of c-Jun N-terminal kinases (JNK), but not of extracellular signal-regulated kinase (ERK)1/2 and p38. These NiCl(2)-induced apoptosis-related signaling responses could be effectively reversed by specific JNK inhibitor SP600125. To the best of our knowledge, this study is the first to show that Ni causes pancreatic β-cell death through a JNK activation-regulated mitochondria-dependent apoptosis-signaling pathway.
Toxicology 08/2011; 289(2-3):103-11. · 3.68 Impact Factor
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Cheng Chien Yen, Tsung Jung Ho,
Chin Ching Wu,
Chun Fang Chang,
Chin Chuan Su,
Ya Wen Chen,
Tzyy Rong Jinn,
Tien Hui Lu,
Po Wen Cheng,
Yi Chang Su,
Shing Hwa Liu,
Chun Fa Huang
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ABSTRACT: Arsenic pollution is a major public health problem worldwide. Inorganic arsenic (iAs) is usually more harmful than organic ones. iAs pollution increases the risk of human diseases such as peripheral vascular disease and cancer. However, the toxicological effects of iAs in the brain are mostly unclear. Here, we investigated the toxic effects and possible mechanisms of iAs in the cerebrum of mice after exposure to iAs (0.5 and 5 ppm (mg/l) As(2)O(3), via the drinking water), which was the possible human exposed dose via the ingestion in iAs-contaminated areas, for 6 consecutive weeks. iAs dose-dependently caused an increase of LPO production in the plasma and cerebral cortex. iAs also decreased the reduced glutathione levels and the expressions of NQO1 and GPx mRNA in the cerebral cortex. These impairments in the cerebral cortex caused by iAs exposure were significantly correlated with the accumulation of As. Moreover, iAs induced the production of apoptotic cells and activation of caspase-3, up-regulation of Bax and Bak, and down-regulation of Mcl-1 in the cerebral cortex. Exposure to iAs also triggered the expression of ER stress-related genes, including GRP78, GRP94, and CHOP. Meanwhile, an increase of p38 activation and dephosphorylation of ERK1/2 were shown in the cerebral cortex as a result of iAs-exposed mice. These iAs-induced damages and apoptosis-related signals could be significantly reversed by NAC. Taken together, these results suggest that iAs-induced oxidative stress causes cellular apoptosis in the cerebrum, signaling of p38 and ERK1/2, and ER stress may be involved in iAs-induced cerebral toxicity.
Archive für Toxikologie 06/2011; 85(6):565-75. · 4.67 Impact Factor
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ABSTRACT: Qigong, similar to Tai Chi Chuan, is beneficial to health. In Taiwan, Waitankung, a type of Qigong, is as popular as Tai Chi Chuan. This population-based comparison study compares the health-related quality of life between people practicing Waitankung and their comparable community residents.
A total of 165 individuals practicing Waitankung were matched by age and sex with 660 general individuals for comparison. Information about health-related quality of life, measured by the SF-36, and other basic and health conditions was obtained from the questionnaires. This study used the linear mixed-effect regression model to examine the association between health-related quality of life and the practice of Waitankung.
Compared with either sedentary individuals or individuals practicing other types of exercise, the Waitankung group scored higher for eight and five out of ten SF-36 components, respectively. The Waitankung group scored better in general health, vitality, and physical component summary compared to individuals participating in other types of exercise, even when considering the energy expended by exercise.
The results suggest that Waitankung exercising is significantly associated with health-related quality of life. Waitankung may serve as an exercise choice for middle-aged and older people to improve overall quality of life.
BMC Public Health 01/2011; 11:546. · 2.00 Impact Factor
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ABSTRACT: Membranous glomerulonephritis (MGN) is one common cause of idiopathic nephrotic syndrome. Transient receptor potential cation channel 6 (TRPC6) has been identified as causing a familial form of progressive focal and segmental glomerulosclerosis. The objective was to clarify the relationship between TRPC6 polymorphisms and MGN. We recruited a cohort of 134 biopsy-diagnosed MGN patients and 265 healthy subjects. Genotyping of TRPC6 polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analyzed associations between TRPC6 gene polymorphisms and clinical manifestations and pathogenesis of MGN. There was no statistically significant difference of TRPC6 gene rs3824935 C/T, rs17096918 C/T, and rs4326755 A/G polymorphisms between controls and patients with MGN. There was no statistical significance of allele frequencies in these two groups. The characteristics of clinical parameters in TRPC6 gene (rs3284935) C/T polymorphism revealed no difference except proteinuria (p < 0.0005) between CC and non-CC genotype in MGN patients. Besides, no apparent statistically significant differences of rs17096918 C/T (TT and non-TT) and rs4326755 A/G (AA and non-AA) polymorphisms between genotypes were found in the clinical parameters. There is no different genotype distribution between normal controls and patients with MGN of TRPC6 gene. The data also show that TRPC6 gene may not be associated with disease clinical course of MGN.
Renal Failure 07/2010; 32(6):666-72. · 0.82 Impact Factor
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ABSTRACT: Mercury, one of the widespread pollutants in the world, induces oxidative stress and dysfunction in many cell types. Alveolar type II epithelial cells are known to be vulnerable to oxidative stress. Alveolar type II epithelial cells produce and secrete surfactants to maintain morphological organization, biophysical functions, biochemical composition, and immunity in lung tissues. However, the precise action and mechanism of mercury on alveolar type II epithelial cell damage remains unclear. In this study, we investigate the effect and possible mechanism of methylmercury chloride (MeHgCl) on the human lung invasive carcinoma cell line (Cl1-0) and mouse lung tissue. Cl1-0 cells were exposed to MeHgCl (2.5-10 microM) for 24-72 h. The results showed a decrease in cell viability and an increase in malondialdehyde (MDA) level and ROS production at 72 h after MeHgCl exposure in a dose-dependent manner. Caspase-3 activity, sub-G1 contents and annexin-V binding were dramatically enhanced in Cl1-0 cells treated with MeHgCl. MeHgCl could also activate Bax, release cytochrome c, and cleave poly(ADP-Ribose) polymerase (PARP), and decrease surfactant proteins mRNA levels. Moreover, in vivo study showed that mercury contents of blood and lung tissues were significantly increased after MeHgCl treatment in mice. The MDA levels in plasma and lung tissues were also dramatically raised after MeHgCl treatment. Lung tissue sections of MeHgCl-treated mice showed pathological fibrosis as compared with vehicle control. The mRNA levels of proteins in apoptotic signaling, including p53, mdm-2, Bax, Bad, and caspase-3 were increased in mice after exposure to MeHgCl. In addition, the mRNA levels of surfactant proteins (SPs), namely, SP-A, SP-B, SP-C, and SP-D (alveolar epithelial cell functional markers) were significantly decreased. These results suggest that MeHgCl activates an oxidative stress-induced mitochondrial cell death in alveolar epithelial cells.
Toxicology Letters 02/2010; 194(3):70-8. · 3.23 Impact Factor
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ABSTRACT: The aim of this study is pursue the effect of herbal point-patch treatment on allergic rhinitis patients by investigation of the changes of serum total IgE (T-IgE) and eosinophile cationic protein (ECP) levels and through assessment of the results of SF-36 and rhinitis severity questionnaires. A prospective, randomized, single-blind, parallel, controlled study was used. Forty- three eligible participants were selected from outpatients of the Dept. of Ear, Nose, and Throat and Chinese medicine clinic, and 33 eligible participants completed the treatment satisfactorily. Participants used a Chinese herbal point-patch or a placebo patch once a week, for three hours at a time, after being randomly assigned to a control or an experimental group. Each treatment course was three weeks in duration, and each participant underwent two courses of treatment. Before and after each course, participants evaluated the effectiveness of the treatment by completing a questionnaire, and blood samples were collected for T-IgE and ECP analysis. The data revealed that the acupoint herbal patch is a valuable treatment for allergic rhinitis, especially in the symptoms of sneezing, running and itchy nose. The results of the SF-36 indicate a distinct improvement in GH (general health) and VT (vitality) in patients treated with acupoint herbal patches. This study supports the belief that the acupoint herbal patch is an effective treatment for allergic rhinitis and can significantly improve general health, social life and vitality in quality of life.
The American Journal of Chinese Medicine 01/2010; 38(4):661-73. · 1.98 Impact Factor
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Kuang-Chi Lai,
Wei-Yong Lin,
Kee-Ming Man,
Chou-Haung Tsai,
Huey-Yi Chen,
Fuu-Jen Tsai,
Fun-Jou Chen,
Hsin-Yi Chen,
Hsin-Ping Liu, Tsung-Jung Ho,
Po-Hsun Huang,
Po-Len Liu,
Feng-Yen Lin,
Jui-Lung Shen,
Jung-Tung Liu,
Yung-Hsiang Chen,
Wen-Chi Chen
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ABSTRACT: The interleukin-18 (IL-18) encoding gene has three common single-nucleotide polymorphisms at -607C/A, -137G/C and +105A/C, which have been reported to be associated with several diseases. The aim of this study is to test whether IL-18 polymorphisms could act as genetic markers for renal stone disease.
A control group of 104 healthy subjects, and 272 patients with recurrent calcium oxalate stones were examined. Polymerase chain reaction-based restriction endonuclease analysis was used to detect IL-18 polymorphisms.
The patient and control groups differed significantly in genotypic expression of the IL-18 +105A/C polymorphism. The prevalence of the A/C + C/C genotypes in the patients was higher than that in the controls. The allelic frequency of IL-18 +105A/C differed significantly between the patients and the controls. The odds ratio (OR) of the A/C heterozygote of IL-18 +105A/C associated with urolithiasis was 2.772. The OR of the A/C + C/C genotypes of IL-18 +105A/C associated with urolithiasis was 3.097. The OR per copy of the C allele of IL-18 +105A/C associated with urolithiasis was 4.143. There were also significant differences in the prevalence of genotype IL-18 -137G/C polymorphisms between the patients and controls. The distribution of the G/G homozygote in the patients was higher than that in the controls. There was no significant difference in genotype and allelic frequency at the IL-18 -607C/A polymorphism between patients and control subjects.
The results indicate that IL-18 +105A/C polymorphisms may play a role in the development of urolithiasis.
Scandinavian Journal of Urology and Nephrology 12/2009; 44(1):20-6. · 0.99 Impact Factor
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Chinese medical journal 08/2009; 122(13):1587-90. · 0.86 Impact Factor
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ABSTRACT: The onsets of needling sensation introduced by acupuncture stimulus can vary widely from subject to subject. This should be explicitly accounted for by the model blood oxygenation-level dependent (BOLD) time course used in general linear model (GLM) analysis to obtain more consistent across-subject group results. However, in standard GLM analysis, the model BOLD time course obtained by convolving a canonical hemodynamic response function with an experimental paradigm time course is assumed identical across subjects. Although some added-on properties to the model BOLD time course, such as temporal and dispersion derivatives, may be used to account for different BOLD response onsets, they can only account for the BOLD onset deviations to the extent of less than one repetition time (TR).
In this study, we explicitly manipulated the onsets of model BOLD time course by shifting it with -2, -1, or 1 TR and used these temporally shifted BOLD model to analyze the functional magnetic resonance imaging (fMRI) data obtained from three acupuncture fMRI experiments with GLM analysis. One involved acupuncture stimulus on left ST42 acupoint and the other two on left GB40 and left BL64 acupoints.
The model BOLD time course with temporal shifts, in addition to temporal and dispersion derivatives, could result in better statistical power of the data analysis in terms of the average correlation coefficients between the used BOLD models and extracted BOLD responses from individual subject data and the T-values of the activation clusters in the grouped random effects.
The GLM analysis with ordinary BOLD model failed to catch the large variability of the onsets of the BOLD responses associated with the acupuncture needling sensation. Shifts in time with more than a TR on model BOLD time course might be required to better extract the acupuncture stimulus-induced BOLD activities from individual fMRI data.
Chinese medical journal 05/2009; 122(7):823-9. · 0.86 Impact Factor
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ABSTRACT: Developing effective methods for helping athletes recover from muscle fatigue is deemed essential, particularly on the eves' important competitions. This study aimed to investigate the effects of acupuncture stimulation on athletes' recovery abilities. Subjects were selected from 30 male elite university basketball players who were randomly assigned to 3 groups: acupuncture group, sham group, and normal (control) group, each containing 10 subjects. Acupuncture was carried out on each athlete in acupuncture group at the Neiguan (PC6) and Zusanli (ST36) acupoints, beginning at 15 min prior to exercise and continuing until exhaustion of the subject. Similar acupuncture was also carried out on each athlete in the sham group but the positions were 1 cm away from the PC6 and ST36 acupoints. No acupuncture was conducted on the athletes in the normal group. During the experiments, each subject performed separate runs on the treadmill. The data of heart rate (HR(max)), oxygen consumption (VO(2max)), and blood lactic acid were measured during the rest period and at 3 recovery points of time (5th, 30th and 60th min) post-exercise. The results showed that the acupuncture group (PC6 and ST36) has significantly lower HR(max), VO(2max) and blood lactic acid than both the sham and normal groups at the 30th min post-exercise. Blood lactic acid of the acupuncture group was also significantly lower than that of the other two groups in the 60th min post-exercise. Our findings have shed some light on the development of effective acupuncture schemes to enhance the recovery ability for elite basketball athletes.
The American Journal of Chinese Medicine 02/2009; 37(3):471-81. · 1.98 Impact Factor
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ABSTRACT: Carryover effects can contaminate ON/OFF BOLD contrasts designated in an fMRI experiment. Yet, the ON/OFF contrasts are essential to facilitate statistical analysis based on the significance of contrast levels. Here, we conducted an fMRI experiment with acupuncture stimulation applied on ST42 acupoint as well as with tactile stimulation on its skin surface. Experiment consisted of three two-block acupuncture and one two-block tactile fMRI runs. Each block started with 26-sec OFF period followed by either 26-sec needle manipulation in the acupuncture runs or by scratching skin surface with sand paper in the tactile. To test if carryover effects could alter the BOLD contrasts, we analyzed different portions of fMRI data using GLM method. Our results showed analyses on different portions of acupuncture fMRI data gave significantly different results. Statistical parametric maps of group random effects resulted from the analysis on the very first fMRI trial formed the broadest coverage of the active brain areas. BOLD model time course also best explained the adjusted raw time course at peak active voxel (coefficient of determination = 0.88). Analyses on other portions of fMRI data only selected subset of the active brain areas delineated by the analysis on the very first data trial and the BOLD model only mildly accounted for the adjusted raw time courses. In tactile runs, results were more consistent across analyses. Therefore, in fMRI experiments with strong carryover effects, a single-block experimental design with multiple repetitions, separated by long enough periods of time, should be more suitable to extract task BOLD effects.
The American Journal of Chinese Medicine 02/2008; 36(1):55-70. · 1.98 Impact Factor
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ABSTRACT: Previous studies have shown health benefits of T'ai Chi Chuan (TCC). In Taiwan, TCC is a form of exercise that is widely practiced by the elderly. The aim of this cross-sectional study was to investigate the effects of TCC on the health-related quality of life (HRQOL) in the senior population.
Subjects who regularly practiced TCC in Taiwan were selected by random sampling and included 140 seniors (77 males and 63 females, aged 40-70 years). The questionnaire was separated into 2 parts: demographic information and the SF-36 questionnaire, which used 8 domains to evaluate the subjects' HRQOL. The results were compared with those of 560 age- and sex-matched control subjects that were taken from the general population (308 males and 252 females). Multiple regression analysis was used to compare the quality of life in each of the 8 domains between the 2 groups.
The TCC group showed significantly higher quality-of-life scores than the control group in each of the 8 domains with the exception of the bodily pain scales. Using multiple linear regression adjusted for covariates, the TCC group had significantly higher scores in physical functioning, physical roles, general health, vitality, and social-functioning scales than the control group. In most of the domains in both the TCC group and the control group, quality of life became worse with increased age, whereas the scores in vitality and social-functioning domains of the TCC group showed a reverse trend; they remained unchanged or even improved with increased age.
Our study supports the hypothesis that TCC improves quality of life among the elderly in Taiwan, but further study must be conducted to more conclusively show the link between TCC and health-related QOL.
The Journal of Alternative and Complementary Medicine 01/2008; 13(10):1077-83. · 1.59 Impact Factor
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ABSTRACT: The integration of traditional Chinese and Western medicine and their clinical effects have been widely evaluated. Many studies have shown that using a combination of these two remedies has resulted in better outcomes than using only one of them. Acupuncture is a traditional Chinese medical technique, which plays an important role in enforcing pain control, prevention and functional improvement. In 1979, the World Health Organization (WHO) journal introduced acupuncture as a remedy for 43 diseases, including frozen shoulder. This study aims to assess the therapeutic outcomes of combining acupuncture and physical therapy to treat frozen shoulder, and hopes to establish an evidence-based study of the integration of acupuncture and western medicine in the future. A total of 75 frozen shoulder patients treated in a medical center were recruited for the study between January 2002 and December 2002. The average age of these patients was 54.8 years. The average duration of the condition was 25.8 weeks before treatment. Of the 75 patients, 30 were treated by physical therapy, 30 by acupuncture and 15 by both remedies. Before the treatment began, all patients were evaluated by assessing static pain scale, motion pain scale, active and passive ROM (range of motion) and quality of life scale sheet SF-36 (Short Form-36). The outcome was evaluated by follow-up assessments conducted at the 2nd week and 4th week of treatment sessions. All patients showed improvement in quality of life (Short Form-36). Pain was controlled better by acupuncture while ROM improved following physical therapy. However, patients treated by both methods had the best outcome. The integration of acupuncture and physical therapy to treat frozen shoulder leads to a better outcome than using only one method. The author suggests that an evidence-based foundation of the integration of Chinese and Western medicine should be established in the future, to encourage the integration of Chinese and Western medicine.
The American Journal of Chinese Medicine 02/2006; 34(5):759-75. · 1.98 Impact Factor
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The Journal of Alternative and Complementary Medicine 13(1):13-4. · 1.59 Impact Factor
