TCM as adjunctive therapy improves risks of respiratory hospitalizations in persons with type 2 diabetes: A retrospective cohort study.

Patients with type 2 diabetes are at a higher risk of chronic obstructive pulmonary disease (COPD) and asthma than the general population. In addition, emerging evidence suggests that traditional Chinese medicine (TCM) might be beneficial for patients with type 2 diabetes. We investigated whether TCM use was associated with a reduced risk of respiratory hospitalizations in patients with type 2 diabetes. Conducting a retrospective cohort study, we used data retrieved from the NDCMP database. Among 56,035 patients, 5226 were classified as TCM users; 50,809 were classified as TCM nonusers. Both groups were analyzed until the end of 2011 to examine the incidence of respiratory hospitalizations by using a Cox proportional hazards model to evaluate effects of TCM use on respiratory hospitalizations. During the 6-year study follow-up period, the incidence density rates of COPD- and asthma-related hospitalization were estimated to be 13.03 and 4.47 per 10,000 patient-years for TCM nonusers and 10.08 and 3.28 per 10,000 patient-years for TCM users, respectively. The HR of COPD-related hospitalization in TCM users was 0.88 (95% CI = 0.79-0.99); and the HR of asthma-related hospitalization in TCM users was 0.81 (95% CI = 0.66-1.00). Stratified analyses revealed that effects of TCM use were stronger among individuals who had diabetes for <3 years. As a part of Integrative Medicine, our study results demonstrate that TCM use was associated with a significant reduced risk of respiratory hospitalizations, especially in patients with diabetes for <3 years.

Development of a traditional Chinese medicine-based agent for the treatment of cancer cachexia.

BACKGROUND: Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. METHODS: We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy. RESULTS: Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P < 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 µg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles. CONCLUSIONS: All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.

Gait-Related Brain Activation During Motor Imagery of Complex and Simple Ambulation in Parkinson's Disease With Freezing of Gait.

Background: Freezing of gait (FOG) in Parkinson's disease (PD) is a devastating clinical phenomenon that has a detrimental impact on patients. It tends to be triggered more often during turning (complex) than during forwarding straight (simple) walking. The neural mechanism underlying this phenomenon remains unclear and requires further elucidation. Objective: To investigate the differences in cerebral functional magnetic resonance imaging responses between PD patients with and without FOG during explicitly video-guided motor imagery (MI) of various complex (normal, freezing) and simple (normal, freezing) walking conditions. Methods: We recruited 34 PD patients, namely, 20 with FOG and 14 without FOG, and 15 normal controls. Participants underwent video-guided MI of turning and straight walking, with and without freezing, while their brain blood oxygen level-dependent (BOLD) activities were measured. Gait analysis was performed. Results: While comparing FOG turning with FOG straight walking, freezers showed higher activation of the superior occipital gyrus, left precentral gyrus, and right postcentral gyrus compared with non-freezers. Normal controls also manifest similar findings compared with non-freezers, except no difference was noted in occipital gyrus activity between the two groups. Freezers also displayed a higher effect size in the locomotor regions than non-freezers during imagery of normal turning. Conclusions: Our findings suggest that freezers require a higher drive of cortical and locomotion regions to overcome the overinhibition of the pathways in freezers than in non-freezers. Compared with simple walking, increased dorsal visual pathway and deep locomotion region activities might play pivotal roles in tackling FOG in freezers during complex walking.

Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

PURPOSE: Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. METHODS: This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. RESULTS: A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). CONCLUSION: This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

Variability of fasting plasma glucose increased risks of diabetic polyneuropathy in T2DM.

OBJECTIVE: To examine whether variations in fasting plasma glucose (FPG), as measured by the coefficient of variation (CV), is a predictor of diabetic polyneuropathy (DPN) risk, considering glycated hemoglobin (HbA1c) and other traditional risk factors. METHODS: Type 2 diabetic patients enrolled in the National Diabetes Care Management Program were ≥30 years of age and free of DPN (n = 36,152). They were enrolled in 2002-2004 and were monitored until 2011. The related factors were analyzed using Cox proportional hazards regression models. RESULTS: During an average 7.23 years of follow-up, a total of 7,219 incident cases of DPN were identified, with a crude incidence rate of 27.62/1,000 person-years (25.83 for men and 29.31 for women). After multivariate adjustment, both FPG-CV and HbA1c were significant predictors of DPN, with corresponding hazard ratios of 1.14 (95% confidence interval [CI] 1.05-1.23) and 1.15 (95% CI 1.06-1.24) for FPG-CV in the fourth to fifth quintiles and 1.13 (95% CI 1.07-1.20) for HbA1c ≥7%. This finding maintained consistency after excluding potential confounders in the sensitivity analysis, further validating the results. CONCLUSIONS: FPG-CV and HbA1c ≥7% were potent predictors of DPN in type 2 diabetic patients. The associations among HbA1c, glycemic variability, and DPN suggest a linked pathophysiologic mechanism, which may play a crucial role in clinical risk assessments.

Traditional Chinese medicine therapy improves the survival of systemic lupus erythematosus patients.

OBJECTIVE: No previous studies have evaluated the effect of traditional Chinese medicine (TCM) treatment on the survival of patients with systemic lupus erythematosus (SLE). Hence, in this study, we determined whether TCM treatment affects the survival of SLE patients. METHODS: This nationwide population-based retrospective cohort study assessed 23,084 patients newly diagnosed with SLE between 1999 and 2009, using the database of the Taiwan National Health Insurance program. RESULTS: Among these patients, 9267 (40.15%) used TCM for SLE treatment and exhibited a significantly decreased risk of death [hazard ratio (HR) = 0.73; 95% confidence interval (CI): 0.68-0.78], with multivariate adjustment, compared with those without TCM use. A similar significant protective effect of TCM use was found across various subgroups of comorbidities. TCM use 1 year before diagnosis also reduced the risk of death. Our study findings indicated that Zhi Bo Di Huang Wan (HR = 0.54; 95% CI: 0.32-0.91), Jia Wei Xiao Yao San (HR = 0.35; 95% CI: 0.16-0.73), Liu Wei Di Huang Wan (HR = 0.51; 95% CI: 0.28-0.93), Gan Lu Yin (HR = 0.40; 95% CI: 0.17-0.96), and Yin Qiao San (HR = 0.22; 95% CI: 0.05-0.86) were the most effective TCM agents that improved survival. CONCLUSIONS: This nationwide retrospective cohort study provided information that combined therapy with TCM may improve the survival in SLE patients. This study also suggests that TCM may be used as an integral element of effective therapy for SLE.

Time-trend analysis of prevalence, incidence and traditional Chinese medicine use among children with asthma: a population-based study.

BACKGROUND: This study determined annual prevalence and incidence trends of asthma among children in Taiwan from 2002 to 2008. Risk factors and traditional Chinese medicine (TCM) use were examined. METHODS: A random sample was selected for a population-based study with a selection probability of 0.5 from all 3-18 years insurants. The annual prevalence and incidence of asthma were estimated according to age, sex, insurance premium and degree of urbanization. RESULTS: The prevalence of asthma increased from 12.99% in 2002 to 16.86% in 2008. The increase was greatest in 2008, among boys, 11-15 years, ≥medium insurance premium, and high- and medium-density urban area. TCM use in asthma-prevalent children decreased from 1.16% in 2002 to 0.59% in 2008. The incidence fluctuated, ranging from 1.01% in 2002 to 1.49% in 2005. The highest was in 2005, among boys, 3-5 years, ≥medium insurance premium and high-density urban area. TCM use in asthma-incident children decreased from 3.59% in 2002 to 1.69% in 2008. CONCLUSION: This study demonstrated a substantial increase in annual prevalence of asthma among children in Taiwan from 2002 to 2008. The incidence fluctuated. The TCM use showed a decreasing linear trend and was higher in incident than in prevalent cases.

Hospice shared-care saved medical expenditure and reduced the likelihood of intensive medical utilization among advanced cancer patients in Taiwan--a nationwide survey.

PURPOSE: Hospice shared care (HSC) is a new care model that has been adopted to treat inpatient advanced cancer patients in Taiwan since 2005. Our aim was to assess the effect of HSC on medical expenditure and the likelihood of intensive medical utilization by advanced cancer patients. METHODS: This is a nationwide retrospective study. HSC was defined as using "Hospice palliative care (HPC) teams to provide consultation and service to advanced cancer patients admitted in the nonhospice care ward." There were 120,481 deaths due to cancer between 2006 and 2008 in Taiwan. Patients receiving HSC were matched by propensity score to patients receiving usual care. Of the 120,481 cancer deaths, 12,137 paired subjects were matched. Medical expenditures for 1 year before death were assessed between groups using a database from the Bureau of National Health Insurance. Paired t and McNemar's tests were applied for comparing the medical expenditure and intensive medical utilization before death between paired groups. RESULTS: Compared to the non-HSC group, subjects receiving HSC had a lower average medical expenditure per person (US$3,939 vs. US$4,664; p<0.001). The HSC group had an adjusted net savings of US$557 (13.3%; p<0.001) in inpatient medical expenditure per person compared with the non-HSC group. Subjects that received different types of HPC had 15.4-44.9% less average medical expenditure per person and significantly lower likelihood of intensive medical utilization than those that did not receive HPC. CONCLUSIONS: HSC is associated with significant medical expenditure savings and reduced likelihood of intensive medical utilization. All types of HPC are associated with medical expenditure savings.

Certain bio-psychosocial-spiritual problems associated with dyspnea among advanced cancer patients in Taiwan.

PURPOSE: Dyspnea is a multidimensional phenomenon among advanced cancer patients. We aim to explore the association between bio-psychosocial-spiritual problems and dyspnea among advanced cancer patients in Taiwan. METHODS: We retrospectively analyzed advanced cancer patients admitted to the hospice palliative ward in a tertiary hospital in Taiwan from 2002 to 2005. A total of 687 consecutive advanced cancer patients were enrolled. Physical, psychosocial, and spiritual problems for each patient were collected. Multiple logistic regression analyses were used to evaluate the association between dyspnea and other physical, psychosocial, and spiritual problems. RESULTS: The top four primary sites of cancer among these patients are the liver/biliary tract (19.9%), lung (15.6%), colon/rectum (12.8%), and head/neck (9.9%). During admission period, 260 (37.8%) patients experienced dyspnea. For primary cancer types and metastatic locations, subjects with dyspnea tended to have lung cancer, lung metastasis, or brain metastasis. The clinical symptoms/signs related to dyspnea are pain, anorexia, constipation, nausea/vomiting, coughing, pleural effusion, edema, anxiety, and propriety preparation problem, that is, arranging one's will, feelings of isolation, fear of death, and survival. After further adjustments for potential confounders, subjects with problems of propriety preparation were found to be strongly associated with dyspnea. The adjusted odds ratio of having dyspnea caused by the problem of propriety preparation was 1.91 (95% confidence interval, 1.15-3.19). CONCLUSIONS: Advanced cancer patients with certain psychosocial and spiritual problems, such as, the problem of propriety preparation, fear of death, and anxiety, tended to have dyspnea. Among these factors, propriety preparation plays an important role among dyspnea patients. Advanced cancer patients with dyspnea have greater needs for propriety preparation.

Coffee consumption is inversely associated with type 2 diabetes in Chinese.

BACKGROUND: Coffee consumption has been shown to be inversely associated to type 2 diabetes mellitus (T2DM), but evidence in Chinese populations is limited. We investigated the relationship between coffee consumption and T2DM in a population-based cohort of middle-aged Chinese. MATERIALS AND METHODS: We studied 2332 subjects who participated in the Taichung Community Health Study in Taiwan in 2004. The relationships between coffee consumption, T2DM and fasting glucose were assessed. RESULTS: The prevalence of T2DM was 14·0% and 10·4% in men and women. After adjustment for age, body mass index, blood pressure, smoking, alcohol drinking, betel nut chewing, physical activity, income, education level, fat%, protein%, carbohydrate% and magnesium, coffee intake was inversely associated with T2DM. Habitual coffee drinkers had 38-46% lower risk of T2DM than nondrinkers. Compared to nondrinkers, the adjusted odds ratios (ORs) for T2DM according to subjects with habitual coffee consumption (<1, 1-6, ≥7 times per week) were 0·77 (0·52-1·13), 0·46 (0·28-0·76) and 0·37 (0·16-0·83), respectively. The decreasing ORs indicate a dose-response effect of coffee consumption on the likelihood of having T2DM (P<0·001). A similar relationship was also evident in newly diagnosed T2DM (P<0·05). The adjusted mean fasting glucose levels gradually decreased as the frequency of coffee consumption increased (P<0·05). CONCLUSIONS: Coffee intake is inversely associated with T2DM in Chinese. Coffee may be a protective agent for T2DM in Chinese.

Peroxisome proliferator-activated receptor gamma transactivation-mediated potentiation of glucose uptake by Bai-Hu-Tang.

ETHNOPHARMACOLOGICAL RELEVANCE: The molecular mechanism of a traditional hypoglycemic Chinese herbal formula. AIM OF THE STUDY: To explore the glucose uptake effect as well as the mechanism(s) of action of Bai-Hu-Tang (BHT), a traditional Chinese herbal formula, composed of anemarrhena, gypsum, licorice and rice. MATERIALS AND METHODS: Differentiated 3T3-L1 adipocytes were treated with vehicle, insulin or insulin plus different concentrations of BHT. The 2-deoxy-[(3)H] glucose uptake assay was performed to measure the amount of glucose uptake. To explore the mechanism(s) of glucose uptake of BHT, we used two insulin signaling transduction inhibitors, N-Acetyl-Leu-Leu-Norleu-al (ALLN), a calpain inhibitor, and LY 294002, a phosphatidylinositol (PI)3-kinase inhibitor, to test if the glucose uptake effect was mediated by the insulin signaling pathway. We then used Western blot analysis to re-confirm the result of the insulin signaling inhibition assay. Finally, reporter chimera assay of HuH-7 cells was used to measure the peroxisome proliferator-activated receptor gamma (PPARgamma) activation by BHT. RESULTS: BHT potentiated insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The effect of BHT-stimulated glucose uptake was neither inhibited by ALLN nor by LY 294002. The protein expression of PI3 kinase pathway did not change after BHT stimulation. PPARgamma activation was elevated by 67.7+/-32% (p<0.05) in HuH-7 cells treated with 0.8 microg/ml of BHT. CONCLUSIONS: BHT stimulated glucose uptake in 3T3-L1 adipocytes. This effect was via PPARgamma activation rather than via the insulin signaling pathway.