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The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1β, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.

Background Traditional Chinese medicine and western medicine have coexisted since 1958 in Taiwan. Integrative traditional Chinese and western medicine (TC&WM) remains to be studied and promoted. In response to the documentary report of WHO Traditional Medicine Strategy 2002–2005, the present study was planned and carried out. Methods During 2004–2008, 19 integrative TC&WM dialogue forums were held, in which 219 TC&WM scholars and professionals participated by invitation. The proceedings of the forums in Chinese were published. A study team was organized in 2009 to collect the consensus opinions, utilizing a Delphi method. The opinions collected were discussed in an international TC&WM forum held on November 1, 2014. Results The opinions of TC&WM experts and professionals on the integrative issues and values were quite divergent. Of the 39 integrative issues, 34 (87.8%) reached consensus, agreeing that WM is excellent in the diagnosis and treatment of diseases/disorders, yet is still evolving, and not perfect without defects. TCM is patient-centered, wellness-oriented, inadequate for acute, critical and life-threatening diseases, but has a complementary and alternative role to WM. Of the 44 diseases/disorders, 36 (81.8%) reached consensus, worthy for integrative clinical use or trials. Conclusions Integrative TC&WM, combining the best features of two systems, could be a most useful and advanced healthcare medicine in the future, requiring development of regulations and guidelines for the use of TCM and more rigorous efforts have to be made in clinical trials.

This study aimed to investigate whether the use of levonorgestrel intrauterine devices (LNG-IUD) in the perspective of traditional Chinese medicine (TCM) can improve the body constitution deviations and quality of life (QoL) in patients with chronic pelvic pain (CPP) and heavy menstrual bleeding (HMB).To understand the TCM body constitution differences between patients, patients with CPP from a gynecology clinic were first compared to a healthy control group from the Academia Sinica Taiwan Biobank (TWB). Patients with CPP were also compared with patients with pelvic diseases from the TWB. Patients with CPP and HMB, some who under LNG-IUD treatment, underwent tests for physical consistency. After 6-8 months, the TCM body constitution and QoL of patients who received LNG-IUD treatment were reanalyzed. The questionnaires used included the Self-Assessment Chart of Menstrual Bleeding, the Taiwanese version of the Pictorial Blood Loss Assessment Chart, the TCM Body Constitution Questionnaire, the 6-point Behavior Rating Scale, and the Taiwanese version of the Short Form-36 Health Survey. All data were analyzed using Wilcoxon's signed-rank test in SAS 9.4 software.In total, 2932 healthy women and 724 women with pelvic diseases were present in the TWB project. Moreover, 376 patients with CPP were admitted to a gynecology clinic, of whom 42 received LNG-IUD treatment. After LNG-IUD treatment, the primary endpoint was regarded as an improvement in Yang-Xu (lack of energy), Yin-Xu (lack of material), and phlegm stasis (accumulation of pathological products). These findings indicated an improvement in menstrual blood loss, pelvic pain, physical functioning, physical problems, body pain, general health, and emotional problems (p 0.05).LNG-IUD treatment improves body constitution deviations in TCM and QoL in patients with CPP and HMB. Our results provide a valuable reference for the use of modern medicine and TCM in treating CPP and HMB.

Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy.This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks.During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%).NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Graphical abstract, Highlights • A herb-based formula delivers positive clinical outcomes on COVID-19 patients. • The formula inhibits SARS-CoV-2 pathogenesis in anti-viral & -inflammatory assays. • Real-world-evidence offers insights to inform drug development. • Bed-to-bench approach shortens the time required for finding effective therapeutics., COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.

Pulse diagnosis researches acquiring pulse waves from the wrist radial artery has not yet addressed the issue of whether this information is affected by differences in the hemodynamic characteristics of pressure waves derived from different locations. This study aimed to clarify whether the blood dynamic states are identical with regard to the "three positions and nine indicators" ((Equation is included in full-text article.)) listed in traditional Chinese medicine (TCM).A total of 37 participants of CAD group and 20 participants of healthy group were recruited, and pressure pulse waves were measured at 18 locations on both hands. A multivariate analysis (MANOVA) was performed with a "randomized block design" using SPSS 22.0 and R 3.4.1 to examine the time-domain parameters that represented certain hemodynamic characteristics.In CAD group, the results showed significant differences (p0.05) among the h1, h2, h3, h1/t, and h3/h1 measurements of the pulse waves using different indicators at the same position; the h1, h2, h3, and h1/t measurements of the pulse waves at different positions using the indicator "Superficial"; and the h1, h2, h3, h1/t, and h3/h1 measurements of the pulse waves at different positions using the indicator "Medium". In healthy group, the results showed significant differences (p0.05) among the h1, h2, h3, and h1/t measurements of the pulse waves using different indicators at the same position; the h1, h2, and h1/t measurements of the pulse waves at different positions using the same indicator.Because of the differences in the hemodynamic characteristics among the different positions and indicators, the article might provide a new opinion for future pulse diagnosis investigations to carefully consider the measurement location to ensure the completeness of the information.

Not all patients with angina pectoris have coronary artery stenosis. To facilitate the diagnosis of coronary artery disease (CAD), we sought to identify predictive factors of pulse spectrum analysis, which was developed by Wang and is one technique of modern pulse diagnosis. The patients suffered from chest pain and received cardiac catheterization to confirm the CAD diagnosis and Gensini score were recruited. Their pulse waves of radial artery were recorded. Then, by performing a fast Fourier transform, 10 amplitude values of frequency spectrum harmonics were obtained. Each harmonic amplitude was divided by the sum of all harmonic amplitude values, obtaining the relative percentages of 10 harmonics (C1-C10). Subsequently, multivariate logistic regression was conducted with two models and the areas under the receiver operating characteristic curves (ROC) of these 2 models were compared to see if combining the pulse diagnosis parameters with the risk factor of CAD can increase the prediction rate of CAD diagnosis. The predictive factors of CAD severity were analyzed by multivariate linear regression. A total of 83 participants were included; 63 were diagnosed CAD and 20 without CAD. In the CAD group, C1 was greater and C5 was lower than those of the non-CAD group. The CAD risk factors were put alone in Model 1 to perform the multivariate logistic regression analysis which had a prediction rate of 77.1%; while putting the C1 and C5 harmonics together with the risk factors into Model 2, the prediction rate increased to 80.7%. Finally, the area under ROC of Model 1 and Model 2 was 0.788 and 0.856, respectively. Furthermore, left C1, left C5, gender, and presence of hyperlipidemia were predictors of CAD severity. Therefore, pulse spectrum analysis may be a tool to facilitate CAD diagnosis before receiving cardiac catheterization. The harmonics C1 and C5 were favorable predictive indicators.

Background. Identifying patients with high risk of coronary artery disease (CAD) is often difficult in outpatient clinic settings. This study aimed to explore if the measurement of body constitution can be adopted to predict the risk of CAD diagnosis. The objective of this study is to conduct a prospective observational study and a case-control study to answer the research question. Study Design. Part 1 (prospective observational study): a total of 143 patients with chest pain and admitted to receive cardiac catheterization were enrolled, and 108 of them were diagnosed with CAD. Part 2 (case-control study): the above 108 CAD patients and 476 healthy controls matched by age and gender from the participants of Taiwan Biobank were adopted for comparison. Main Outcome Measures. The body constitution of both patients and healthy controls were measured by the Body Constitution Questionnaire (BCQ). Each one received scores of Yang-Xu (Yang-deficiency), Yin-Xu (Yin-deficiency), and Stasis. These 3 scores together with demographic characteristics and CAD risk factors were used in the logistic multiple regression model to predict the risk of CAD. Results. (Part 1) No difference was found between the scores of Yang-Xu, Yin-Xu, and Stasis between the patients with and without CAD. (Part 2) The scores of Yang-Xu, Yin-Xu, and Stasis of the CAD patients were significant higher those of the healthy controls. Yang-Xu and Stasis scores were obtained with age, BMI, and hypertension in the model with prediction rate 89.0%. The area under receiver operating characteristic curve of this model was 0.896. Conclusions. This study is the first to apply Chinese body constitution concepts and measurable variables to assess the risk of having CAD of the patients with chest pain prior to receiving cardiac catheterization. The higher scores of Yang-Xu and Stasis were found to be risk factors. Our results revealed that BCQ has the potential to be a first-line diagnostic tool for patients with chest pain to facilitate early recognition and diagnosis of CAD.

This study investigated the chemical composition, in vitro cytotoxicity, anti-mildew, and anti-wood-decay fungal activities of the essential oil isolated from the fruit of Liquidainbar formosana from Taiwan. The essential oil from the fresh fruit was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. A total of 45 compounds were identified, representing 98.5% of the essential oil. The main components identified were a-pinene (16.8%), β-caryophyllene (10.1%), τ-muurolol (8.3%), τ-cadinol (7.6%), β-pinene (6.7%), and sabinene (5.7%). The essential oil exhibited cytotoxic activity against human oral, liver, and lung cancer cells. The active source compounds were β-caryophyllene, τ-cadinol, and τ-muurolol. The fruit essential oil was shown to have excellent anti-mildew and anti-wood-decay fungal activities, the active compounds being evaluated as τ-cadinol and τ-muurolol.

Objectives: Suboptimal health status (SHS) is a dynamic state wherein people have not been diagnosed with a disease but tend to develop diseases. People with SHS often experience fatigue and other nonspecific symptoms, which are related to a deviated body constitution in traditional Chinese medicine (TCM). However, the correlation between TCM constitution and SHS has not been adequately investigated. Furthermore, no study has explored the radial pulse analysis—an assistive objective indicator of TCM constitution—in healthy people and people with SHS. Design: A cross-sectional study. Settings/Location: Center for Traditional Medicine, Taipei Veterans General Hospital, Taiwan. Subjects: Sixty-six adults (27 healthy participants and 39 participants with SHS) who were aged 20–39 years. Outcome Measures: The body constitution questionnaire (BCQ) scores, suboptimal health status questionnaire-25 (SHSQ-25) scores, and radial pulse waves detected using sphygmography were recorded. Pulse wave analyses are presented as the ratio of frequency below 10 Hz to that above 10 Hz (SER10), which represent energy changes in organ blood flow. Results: Participants with SHS had significantly higher Yang-Xu, Yin-Xu, and stasis scores of BCQ compared with healthy participants. The SHSQ-25 scores of the participants with SHS were moderately correlated with their Yang-Xu, Yin-Xu, and stasis scores (r = 0.65, 0.66, and 0.72, respectively; all p

Bladder cancer is a common malignancy worldwide. However, there is still no effective therapy for bladder cancer. In this study, we investigated the cytotoxic effects of cantharidin [a natural toxin produced (pure compound) from Chinese blister beetles (Mylabrisphalerata or Mylabriscichorii) and Spanish flies (Cantharis vesicatoria)] in human bladder cancer cell lines (including: T24 and RT4 cells). Treatment of human bladder cancer cells with cantharidin significantly decreased cell viability. The increase in the expressions of caspase-3 activity and cleaved form of caspase-9/-7/-3 were also increased in cantharidin-treated T24 cells. Furthermore, cantharidin increased the levels of phospho-eIF2α and Grp78 and decreased the protein expression of procaspase-12, which was accompanied by the increase in calpain activity in T24 cells. Cantharidin was capable of increasing the intracellular Ca2+and the phosphorylation of protein kinase C (PKC) in T24 cells. The addition of BAPTA/AM (a Ca2+chelator) and RO320432 (a selective cell-permeable PKC inhibitor) effectively reversed the increase in caspase-3 and calpain activity, the phosphorylation levels of PKC and eIF2α and Grp78 protein expression, and the decrease in procaspase-12 expression induced by cantharidin. Importantly, cantharidin significantly decreased the tumor volume (a dramatic 71% reduction after 21 days of treatment) in nude mice xenografted with T24 cells. Taken together, these results indicate cantharidin induced human bladder cancer cell apoptosis through a calcium/PKC-regulated ER stress pathway. These findings suggest that cantharidin may be a novel and potential anticancer agent targeting on bladder cancer cells.

Summary Background The Body Constitution Questionnaire (BCQ) was developed in Taiwan to classify people into body constitution (BC) types based on Traditional Chinese Medicine (TCM) theories. Since the culture of Hong Kong is different from Taiwan, the BCQ must be validated before a wider application can be preceded. Aim and objectives To adapt and validate the Hong Kong version of BCQ in Hong Kong Chinese population. Methods The content validity of BCQ was investigated by the cognitive debriefing with 10 patients and 10 Chinese Medicine Practitioners (CMP). A cross-sectional study of 1084 Chinese patients recruited from TCM and Western Medicine (WM) outpatient clinics to confirm the construct validity, reliability, sensitivity and responsiveness of BCQ. 225 of the patients were assessed after 2 weeks for the test-retest reliability. 404 subjects were followed up to evaluate the responsiveness after 3–6 months. Results Cognitive debriefing confirmed the content validity of the BCQ (HK version) with content validity index of all items ranged from 70 to 100%. 1084 out of 2128 patients (51%) completed the cross-sectional study. The construct validity was confirmed with scaling success rates that ranged from 87.5 to 89.5%, moderate correlations between with SF-12v2 scores, and 3-factors structure with confirmatory factor analysis. The reliability was confirmed by the Cronbach's alphas >0.8 and test-retest reliability (intra-class correlation coefficients >0.8). Conclusion BCQ was adapted and validated on Hong Kong Chinese population. Patients with imbalanced BC types had lower health-related quality of life (HRQOL) than those with balanced BC types, which supported the validity and importance of the body constitution under the concept of TCM.

Aim. To evaluate how health-related quality of life (HRQOL) and traditional Chinese medicine (TCM) constitutions of Yin-Xu, Yang-Xu, and Stasis are related in type 2 diabetes patients. Method. Seven hundred and five subjects were recruited in 2010 for this study from a Diabetes Shared Care Network in Taiwan. Generic and disease-specific HRQOL were assessed by the short form 36 (SF-36) and the diabetes impact measurement scale (DIMS). Constitutions of Yin-Xu, Yang-Xu, and Stasis were then assessed by the body constitution questionnaire (BCQ), a questionnaire consisting of 44 items that evaluate the physiological state based on subjective symptoms and signs. Results. Estimated effects of the Ying-Xu and Stasis on all scales of the SF-36 were significantly negative, while estimated effects of the Yang-Xu on all scales (except for SF, RE, MH, and MCS) were significantly negative. For DIMS, the estimated effects of the Ying-Xu and Stasis on all scales were significantly negative except for Stasis on well-being, while Yang-Xu has a significantly negative effect only on symptoms. Conclusions. This study demonstrates that TCM constitutions of Yin-Xu, Yang-Xu, and Stasis are closely related to a reduction in HRQOL. These findings support the need for further research into the impact of intervention for TCM constitutions on HRQOL in patients with type 2 diabetes.

Chloroacetic acid (CA), a toxic chlorinated analog of acetic acid, is widely used in chemical industries as an herbicide, detergent, and disinfectant, and chemical intermediates that are formed during the synthesis of various products. In addition, CA has been found as a by-product of chlorination disinfection of drinking water. However, there is little known about neurotoxic injuries of CA on the mammalian, the toxic effects and molecular mechanisms of CA-induced neuronal cell injury are mostly unknown. In this study, we examined the cytotoxicity of CA on cultured Neuro-2a cells and investigated the possible mechanisms of CA-induced neurotoxicity. Treatment of Neuro-2a cells with CA significantly reduced the number of viable cells (in a dose-dependent manner with a range from 0.1 to 3mM), increased the generation of ROS, and reduced the intracellular levels of glutathione depletion. CA also increased the number of sub-G1 hypodiploid cells; increased mitochondrial dysfunction (loss of MMP, cytochrome c release, and accompanied by Bcl-2 and Mcl-1 down-regulation and Bax up-regulation), and activated the caspase cascades activations, which displayed features of mitochondria-dependent apoptosis pathway. These CA-induced apoptosis-related signals were markedly prevented by the antioxidant N-acetylcysteine (NAC). Moreover, CA activated the JNK and p38-MAPK pathways, but did not that ERK1/2 pathway, in treated Neuro-2a cells. Pretreatment with NAC and specific p38-MAPK inhibitor (SB203580), but not JNK inhibitor (SP600125) effectively abrogated the phosphorylation of p38-MAPK and attenuated the apoptotic signals (including: decrease in cytotoxicity, caspase-3/-7 activation, the cytosolic cytochrome c release, and the reversed alteration of Bcl-2 and Bax mRNA) in CA-treated Neuro-2a cells. Taken together, these data suggest that oxidative stress-induced p38-MAPK activated pathway-regulated mitochondria-dependent apoptosis plays an important role in CA-caused neuronal cell death.

Pathogenesis of sepsis includes complex interaction between pathogen activities and host response, manifesting highly variable signs and symptoms, possibly delaying diagnosis and timely life-saving interventions. This study applies traditional Chinese medicine (TCM)Zhengdiagnosis in patients with severe sepsis and septic shock to evaluate its adaptability and use as an early predictor of sepsis mortality. Three-year prospective observational study enrolled 126 septic patients. TCMZhengdiagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and blood samples for host response cytokines measurement (tumor necrosis factor-α, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18) were collected within 24 hours after admission to Intensive Care Unit. Main outcome was 28-day mortality; multivariate logistic regression analysis served to determine predictive variables of the sepsis mortality. APACHE II score, frequency ofNutrient-phase heat, andQi-XuandYang-Xu Zhengswere significantly higher in nonsurvivors. The multivariate logistic regression analysis identifiedYang-Xu Zhengas the outcome predictor. APACHE II score and levels of five host response cytokines between patients with and withoutYang-Xu Zhengrevealed significant differences. Furthermore, cool extremities and weak pulse, both diagnostic signs ofYang-Xu Zheng, were also proven independent predictors of sepsis mortality. TCM diagnosis “Yang-Xu Zheng” may provide a new mortality predictor for septic patients.

Aim of the study Stasis body constitution is crucial in making diagnosis and treatment decisions in traditional Chinese medicine (TCM) practice. A reliable tool to assess clinical aspects of Stasis is critically needed in order to maximize its clinical value in TCM and its integrative use with modern medicine (MM). Methodology Stasis -related items were first generated from TCM textbooks and a literature review. The 23-item Stasis Body Constitution Questionnaire (BCQs) was then developed using the Delphi method involving 27 experts with TCM and MM professional training and administered to 958 participants receiving physical examination at a teaching hospital or at the TCM outpatient department. Exploratory and confirmatory factor analyses were conducted to derive and validate the underlying structures of the BCQs. Reliability and validity of each factor was also evaluated. Results Four factors, corresponding to the manifestations of the Stasis level in 4 different areas of the body, were identified: Stasis in the trunk (5 items), head (5 items), body surface (3 items), and gastrointestinal tract (3 items). The Cronbach's α coefficients were acceptable (0.62–0.88) and most intra-class correlation coefficients were >0.7. The agreement of Stasis diagnosis by the BCQs and an experienced TCM doctor was high. Conclusions This TCM-based 16-item BCQs is a reliable and valid tool for evaluating the Stasis body constitution in clinical practice and research.

Ethnopharmacological relevance The regulation policies of substances used in Chinese Herbal Medicine (CHM), have a direct influence on the ability of health providers to practice in the clinic. Aim of the study We set out to assess the truth behind the assumption that practice of CHM in the west is constrained by the regulations imposed by authorities in western countries. Materials and methods For the first part of our study we surveyed and compiled lists of banned and restricted Chinese Materia Medica (CMM) from six countries: USA, UK, Germany, Israel, Canada and Australia. Afterwards, we estimated the relevant importance of the 300 CMM most-commonly-prescribed to the practice of CHM according to prescriptions from 2,000,000 randomly selected patients, from the Taiwanese National Health Insurance Research Database (NHIRD). We then compared both lists and determined the clinical importance of the banned and restricted CMM. Results Except for regulations from Canada, most of the information of banned CMM proved to be difficult to organize. The USA was found to have the least amount of banned herbs, with 9 substances. Canada had the highest amount, with 98. In Germany, Australia, the UK, and Israel 10, 29, 36, 68 banned CMM were found, respectively. Apart from aristolochic acid containing substances, ma huang (麻黃, Ephedra sinica ) was the only CMM banned in all countries. Most of the banned CMM were not found to be among the most-commonly-prescribed according to the NHIRD. Conclusion Authorities should make this information more accessible. No clear relation exists between CHM regulations and any ‘Western’ common denominator, and the amount of banned CMM varied greatly among the surveyed countries. However, even among countries with a larger amount of banned CMM, the majority of these were in the bottom two-thirds in respect to the frequency of their use. Thus, regulations in some western countries surely influence the practice of CHM, however, the variability of CMM have been influenced by regulations only to a limited extent.

The aim of this study was to apply a rigorous traditional Chinese medicine (TCM) body constitution questionnaire (BCQ) to survey the prevalence rate of deviations in body constitution and to explore the health-related lifestyle behavior factors of deviations in body constitution.A cross-sectional study was administered through postal mail. Subjects were recruited from a national organization for breast cancer patients (Taiwan Breast Cancer Alliance).Data were obtained from 311 breast cancer patients by questionnaires including a demographic record sheet, lifestyle behavior scales and the BCQ (Yang-Xu, Yin-Xu, and Stasis). Differences concerning the presence of body constitutions were analyzed by Chi-square tests and analyses of variance, and potential predictive factors were analyzed using multivariate logistic regression.In total, 55.3% of the subjects had a Yang-Xu constitution, 61.0% had a Yin-Xu constitution, and 47.6% had a Stasis constitution. A total of 42.8% of the patients displayed a combination of the three types of body constitutions. Feeling stressed, physical exercise, and favoring fried food were predictors of the combined Yang-Xu, Yin-Xu and Stasis constitutions (p0.05). Staying up late was significantly associated with Yin-Xu (p=0.017), and favoring salty food was significantly associated with Stasis (p=0.019).A high prevalence of deviations in body constitutions was observed in the follow-up stage of breast cancer patients. Increasing the adherence to healthy lifestyle behaviors might strengthen and balance body constitution, which could improve supportive care in breast cancer survivors.

Oxidative degradation of dinitrotoluenes (DNTs) in wastewater was performed using persulfate anions combined with ultrasonic irradiation, wherein a synergistic effect is observed. The batch-wise experiments were carried out to elucidate the influence of various operating parameters on sono-activated persulfate oxidation, including ultrasonic power intensity, persulfate anion concentration, reaction temperature and acidity of wastewater. It is noteworthy that the nitrotoluene contaminants could be almost completely eliminated by virtue of sono-activated persulfate oxidation, wherein sulfate radicals serve as principal oxidants, of which amounts are significantly enhanced via addition of sodium sulfate. Based on the results given by gas chromatograph–mass spectrometer (GC–MS), it is postulated that the methyl group of DNTs preliminarily underwent oxidation pathway into dinitrobenzoic acid, followed by decarboxylation to form 1,3-dinitrobenzene (DNB). In sum, the sono-activated persulfate oxidation is a promising method for treatment of nitrotoluenes in wastewater.

Oxidative stress was demonstrated to promote the progression of diabetes mellitus (DM). It has been suggested that copper may play a specific role in the progression and pathogenesis of DM. Pyrrolidine dithiocarbamate (PDTC), a widely apply to the medicine, was known to be capable of enhancing copper accumulation. In this study, we investigated the effect of submicromolar-concentration Cu(2+)/PDTC complex on pancreatic β-cell damage and evaluated the role of oxidative stress in this effect. CuCl(2) (0.01-300μM) did not affect the cell viability in β-cell line RIN-m5F cells. However, combination of CuCl(2) (0.5μM) and PDTC (0.3μM) markedly reduced RIN-m5F cell viability. Cu(2+)/PDTC complex could also increase the LPO and decrease the intracellular reduced GSH levels, and display several features of apoptosis signals including: increase in sub-G1 cell population, annexin-V binding, and caspase-3 activity, mitochondrial dysfunctions, and the activation of PARP and caspase cascades, which accompanied with the marked increase the intracellular Cu(2+) levels. These apoptotic-related responses of Cu(2+)/PDTC complex-induced could be effectively prevented by antioxidant N-acetylcysteine (NAC). Furthermore, Cu(2+)/PDTC complex was capable of increasing the phosphorylations of ERK1/2 and JNK, and its upstream kinase MEK1/2 and MKK4, which could be reversed by NAC. Transfection with ERK2- and JNK-specific si-RNA and specific inhibitors SP600125 and PD98059 could inhibit ERK1/2 and JNK activation and attenuate MMP loss and caspase-3 activity induced by the Cu(2+)/PDTC complex. Taken together, these results are the first report to demonstrate that the Cu(2+)/PDTC complex triggers a mitochondria-regulated apoptosis via an oxidative stress-induced ERK/JNK activation-related pathway in pancreatic β-cells.

Background Nowadays, the individual differences are emphasized in personalized medicine. Traditional Chinese Medicine (TCM) which prescribes tailored treatment based on each patient's different body constitution may provide new strategy to break the bottleneck of modern medicine (MM). Therefore, to integrate TCM into MM, an objective, reliable and rigorous diagnostic tool is necessary for the assessment of TCM constitution of each individual. This study aimed to develop a provisional version of the Yin-Xu Constitution Questionnaire (BCQ-), because evaluating the level of individual's Yin deficiency (Yin-Xu) by his manifestations is frequently involved in TCM clinical trials. Methods The provisional version of BCQ- was developed using a step-by-step approach: 1) to form the research team and select a panel of 26 experts who had both MM and TCM educational background and professional training for Delphi method; 2) to generate questionnaire items from literature review and Delphi process, refine these items to be colloquially acceptable, and evaluate their face and content validities by Delphi process again; 3) to evaluate the difficulty of answering these questions by a pilot study with 81 participants whose age ranged from 20 to 60 years. Results After 2 rounds of Delphi process, 22 colloquially appropriate questions were established and answered without difficulty by the 81 participants. Conclusions This provisional version of BCQ- appeared to have considerable face and content validities and may be the basis to develop an advanced Yin-Xu questionnaire. The reliability and validity of BCQ- were further tested in the second part of the study.

Background: Based on the Traditional Chinese Medicine (TCM) theory and guided by the principles of modern medicine (MM), we aimed to develop an effective and reliable diagnostic tool using self-reported data in order to assess the Yin-Xu body constitution. In this study, we further evaluated a provisional 22-item version of the Yin-Xu Body Constitution Questionnaire (BCQ–) previously derived from the Delphi process. Methods: A total of 1,272 eligible participants aged between 20 and 60 years was recruited. The participants had received health examination in teaching hospitals and had not shown any disease onset in the prior month. The factor structure of the BCQ– was explored, and the reliability and validity of each derived factor (scale) were evaluated. Results: Exploratory factor analysis revealed 5 factors corresponding to the manifestations of the diminishing Yin-Xu level in 5 different body areas: head, 4 limbs, gastrointestinal tract, body surface, and abdominal cavity. 3 items with low factor loading (Conclusions: The final BCQ– measures the Yin-Xu constitution of 5 different body areas. The questionnaire is a reliable, valid, and potentially useful instrument for evaluating the Yin-Xu constitution in clinical research and practice.

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN6 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, and Nov) family of matricellular proteins. However, the effects of CCN6 on human chondrosarcoma cells are largely unknown. In this study, we found that CCN6 increased the migration and the expression of intercellular adhesion molecule-1 (ICAM-1) in human chondrosarcoma cells. αvβ3 and αvβ5 integrin monoclonal antibody and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) inhibited the CCN6-induced increase of the migration and ICAM-1 up-regulation of chondrosarcoma cells. CCN6 stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK, and extracellular signal-regulated kinase (ERK). In addition, activator protein-1 (AP-1) inhibitors suppressed the cell migration and ICAM-1 expression enhanced by CCN6. Moreover, CCN6 increased AP-1 luciferase activity and binding of c-Jun to the AP-1 element on the ICAM-1 promoter. Taken together, our results indicate that CCN6 enhances the migration of chondrosarcoma cells by increasing ICAM-1 expression through the αvβ3 and αvβ5 integrin receptor, FAK, MEK, ERK, c-Jun, and AP-1 signal transduction pathway. J. Cell. Physiol. 227: 223–232, 2012. © 2011 Wiley Periodicals, Inc.

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Integrins are the major adhesive molecules in mammalian cells and have been associated with metastasis of cancer cells. Insulin-like growth factor-I (IGF)-I plays an important role in regulating cell growth, proliferation, survival, and metabolism. However, the effects of IGF-I in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that IGF-I increased the migration and the expression of α5β1 integrin in human chondrosarcoma cells. Pretreatment of cells with IGF-I receptor antibody reduced IGF-I-induced cell migration and integrin expression. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor-κB (NF-κB) pathways after IGF-I treatment were demonstrated, and IGF-I-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and NF-κB cascades. Taken together, our results indicated that IGF-I enhances the migration of chondrosarcoma cells by increasing α5β1 integrin expression through the IGF-I receptor/PI3K/Akt/NF-κB signal transduction pathway. J. Cell. Physiol. 226: 3270–3277, 2011. © 2011 Wiley Periodicals, Inc.

Methylmercury (MeHg) is well-known for causing irreversible damage in the central nervous system as well as a risk factor for inducing neuronal degeneration. However, the molecular mechanisms of MeHg-induced neurotoxicity remain unclear. Here, we investigated the effects and possible mechanisms of MeHg in the mouse cerebrum (in vivo) and in cultured Neuro-2a cells (in vitro). In vivo study showed that the levels of LPO in the plasma and cerebral cortex significantly increased after administration of MeHg (50μg/kg/day) for 7 consecutive weeks. MeHg could also decrease glutathione level and increase the expressions of caspase-3, -7, and -9, accompanied by Bcl-2 down-regulation and up-regulation of Bax, Bak, and p53. Moreover, treatment of Neuro-2a cells with MeHg significantly reduced cell viability, increased oxidative stress damage, and induced several features of mitochondria-dependent apoptotic signals, including increased sub-G1 hypodiploids, mitochondrial dysfunctions, and the activation of PARP, and caspase cascades. These MeHg-induced apoptotic-related signals could be remarkably reversed by antioxidant NAC. MeHg also increased the phosphorylation of ERK1/2 and p38, but not JNK. Pharmacological inhibitors NAC, PD98059, and SB203580 attenuated MeHg-induced cytotoxicity, ERK1/2 and p38 activation, MMP loss, and caspase-3 activation in Neuro-2a cells. Taken together, these results suggest that the signals of ROS-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic pathways that are involved in MeHg-induced neurotoxicity.

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.

Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. This study is the first to investigate the anti-cancer effects of the new benzimidazole derivative (5-methyl-2(pyridine-3-yl)-1-(3,4,5-trimethoxybenzyl)benzimidazole; MPTB) in human chondrosarcoma cells. MPTB-induced cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353 but not in primary chondrocytes. MPTB-induced upregulation of Bax and Bak and dysfunction of mitochondria in chondrosarcoma. MPTB triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol calcium levels, and increased glucose-regulated protein (GRP) expression. MPTB also increased calpain expression. Transfection of cells with GRP78 or calpain siRNA reduced MPTB-mediated cell apoptosis in JJ012 cells. Importantly, animal studies have revealed a dramatic 44% reduction in tumor volume after 21 d of treatment. This study demonstrates novel anti-cancer activity of MPTB against human chondrosarcoma cells and in murine tumor models. Mol. Carcinog. ©2011 Wiley-Liss, Inc.