Ching-Mao Chang

Quantitative assessment of mitochondrial DNA copies from whole genome sequencing

BackgroundMitochondrial dysfunction is associated with various aging diseases. The copy number of mtDNA in human cells may therefore be a potential biomarker for diagnostics of aging. Here we propose a new computational method for the accurate assessment of mtDNA copies from whole genome sequencing data.ResultsTwo families of the human whole genome sequencing datasets from the HapMap and the 1000 Genomes projects were used for the accurate counting of mitochondrial DNA copy numbers. The results revealed the parental mitochondrial DNA copy numbers are significantly lower than that of their children in these samples. There are 8%~21% more copies of mtDNA in samples from the children than from their parents. The experiment demonstrated the possible correlations between the quantity of mitochondrial DNA and aging-related diseases.ConclusionsSince the next-generation sequencing technology strives to deliver affordable and non-biased sequencing results, accurate assessment of mtDNA copy numbers can be achieved effectively from the output of whole genome sequencing. We implemented the method as a software package MitoCounter with the source code and users guide available to the public at http://sourceforge.net/projects/mitocounter/.

Prescription patterns of traditional Chinese medicine for peptic ulcer disease in Taiwan: A nationwide population-based study

ETHNOPHARMACOLOGICAL RELEVANCE Peptic ulcer disease is a common digestive disease. There is a lack of large-scale survey on the use of traditional Chinese medicine (TCM) for the treatment of peptic ulcer disease. This study aimed to investigate the utilization of TCM for the treatment of peptic ulcer disease in Taiwan. MATERIALS AND METHODS We analyzed a random sample comprised of one million individuals with newly diagnosed peptic ulcer disease between 2001 and 2010 from the National Health Insurance Research Database in Taiwan. Demographic characteristics and TCM usage, including Chinese herbal formulas and the single herbs prescribed for patients with peptic ulcer disease, were analyzed. RESULTS A total of 96,624 newly diagnosed subjects with peptic ulcer disease were included. 14,983 (15.5%) patients were TCM users. People residing in highly urbanized areas, younger people and female (compared with male) were more likely to use TCM. With regard to the comorbidities, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus and liver cirrhosis and stroke. The average time between onset of peptic ulcer disease and the first visit to a TCM clinic was 4.7 months. Majority of the patients (n=14,449; 96.4%) received only Chinese herbal remedies. The most frequently prescribed Chinese herbal formula and single herb was Ban-Xia-Xie-Xin-Tang (Pinelliae Decoction to Drain the Epigastrium) and Hai-Piao-Xiao (Os Sepiae), respectively. The core pattern analysis showed that combination of Ban-Xia-Xie-Xin-Tang, Hai-Piao-Xiao (Os Sepiae), Yan-Hu-Suo (Rhizoma Corydalis), Bei-Mu (Bulbus Fritillariae Thunbergii) and Chuan-Lian-Zi (Fructus Toosendan) was most frequently used for peptic ulcer disease. CONCLUSIONS Our study identified the core prescription patterns of TCM for patients with peptic ulcer disease in Taiwan. Further basic and clinical studies are necessary to elucidate the efficacy and mechanisms.

Adjunctive Chinese Herbal Medicine therapy improves survival of patients with chronic myeloid leukemia: a nationwide population-based cohort study.

Despite good clinical results of current drugs, a good reason still exists to search for additional therapies for the management of Chronic Myeloid Leukemia (CML). Chinese Herbal Medicine (CHM) has thus far been overlooked by researchers and no data exists on the subject. We studied the impact of adjunctive CHM on the disease course of CML, using mortality as the major outcome measurement. We used the Taiwanese National Health Insurance Research Database to perform a nationwide population‐based cohort study. Our study included CML patients diagnosed between 2000 and 2010. We matched groups according to age, sex, Charlson Comorbidity Index (CCI) score and use of imatinib, and compared the Hazard Ratios (HR) of CHM group and non‐CHM users, as well as characterized trends of prescriptions used for treating CML. 1371 patients were diagnosed with CML in the years examined, of which 466 were included in to this study. We found that the HR of CHM group was significantly lower compared to non‐CHM groups (0.32, 95% CI 0.22–0.48, P < 0.0001). We also established that this association between reduced HR was dose‐dependent, and the longer CHM users received prescriptions, the lower the HR (P < 0.01). We also analyzed the most commonly used herbal products as well as the HR associated to their use, thus providing future research candidates. Our results supply a strong reason to assume that when administered by properly trained physicians, CHM may have a substantial positive impact on the management of CML.

Perimenopause and incidence of depression in midlife women: a population-based study in Taiwan

ABSTRACT Aim To examine the relationships between depressive symptoms, menopausal status, and menopausal symptoms in middle-aged women. Material and methods This cross-sectional, population-based study involved patients in the Taiwanese community. Data were retrieved from the nationwide 2002 Health Promotion Knowledge, Attitude, and Performance Survey in Taiwan. We assessed depressive symptoms using the Taiwanese Depression Questionnaire with a cut-off point of 18 of 19. Self-reported perception of menopausal status, frequency of menstrual periods in the preceding 12 months, and a history of oophorectomy surgery were used to categorize the womens menopausal status into premenopause, perimenopause, postmenopause, and surgical menopause. Results A total of 3359 women aged 40–55 years were selected. Among these patients, 145 women (4.7%) experienced higher levels of concurrent depressive symptoms. The increase in depressive symptoms was significantly associated with menopausal status and most of the menopausal symptoms. After controlling for age, marital status, education, income, smoking, hormone therapy, and menopause symptoms, multivariate logistic regression showed that perimenopause was still significantly associated with depression in midlife women (odds ratio 1.97; 95% confidence interval 1.24–3.14). Conclusion Independent of menopausal symptoms, perimenopausal status increases the risk of depression.

Corrigendum: The Core Pattern Analysis on Chinese Herbal Medicine for Sjögren's syndrome: A Nationwide Population-Based Study.

The Core Pattern Analysis on Chinese Herbal Medicine for Sjogrens syndrome: A Nationwide Population-Based Study

P02.34. Therapeutic effects of traditional Chinese medicine in cancer patients undergoing chemotherapy or radiotherapy: randomized, double-blind controlled trial

Purpose Cancer is one of the most major health issues worldwide. An increasing number of cancer patients received surgery, chemotherapy and radiotherapy. However, there usually exists some side-effects. Traditional Chinese Medicine (TCM) is one of the most common complementary therapies used in Taiwan. We designed a randomized, doubleblind and placebo-controlled clinical trial to evaluate the role of TCM on patients with cancer.

Traditional Chinese Medicine Use among Patients with Psoriasis in Taiwan: A Nationwide Population-Based Study.

Traditional Chinese medicine (TCM) has long been used for patients with psoriasis. This study aimed to investigate TCM usage in patients with psoriasis. We analyzed a cohort of one million individuals representing the 23 million enrollees randomly selected from the National Health Insurance Research Database in Taiwan. We identified 28,510 patients newly diagnosed with psoriasis between 2000 and 2010. Among them, 20,084 (70.4%) patients were TCM users. Patients who were female, younger, white-collar workers and lived in urbanized area tended to be TCM users. The median interval between the initial diagnosis of psoriasis to the first TCM consultation was 12 months. More than half (N = 11,609; 57.8%) of the TCM users received only Chinese herbal medicine. Win-qing-yin and Bai-xian-pi were the most commonly prescribed Chinese herbal formula and single herb, respectively. The core prescription pattern comprised Mu-dan-pi, Wen-qing-yin, Zi-cao, Bai-xian-pi, and Di-fu-zi. Patients preferred TCM than Western medicine consultations when they had metabolic syndrome, hepatitis, rheumatoid arthritis, alopecia areata, Crohns disease, cancer, depression, fatty liver, chronic airway obstruction, sleep disorder, and allergic rhinitis. In conclusion, TCM use is popular among patients with psoriasis in Taiwan. Future clinical trials to investigate its efficacy are warranted.

Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data

BackgroundNeutrophil antigens are involved in a variety of clinical conditions including transfusion-related acute lung injury (TRALI) and other transfusion-related diseases. Recently, there are five characterized groups of human neutrophil antigen (HNA) systems, the HNA1 to 5. Characterization of all neutrophil antigens from whole genome sequencing (WGS) data may be accomplished for revealing complete genotyping formats of neutrophil antigens collectively at genome level with molecular variations which may respectively be revealed with available genotyping techniques for neutrophil antigens conventionally.ResultsWe developed a computing method for the genotyping of human neutrophil antigens. Six samples from two families, available from the 1000 Genomes projects, were used for a HNA typing test. There are 500 ~ 3000 reads per sample filtered from the adopted human WGS datasets in order for identifying single nucleotide polymorphisms (SNPs) of neutrophil antigens. The visualization of read alignment shows that the yield reads from WGS dataset are enough to cover all of the SNP loci for the antigen system: HNA1, HNA3, HNA4 and HNA5. Consequently, our implemented Bioinformatics tool successfully revealed HNA types on all of the six samples including sequence-based typing (SBT) as well as PCR sequence-specific oligonucleotide probes (SSOP), PCR sequence-specific primers (SSP) and PCR restriction fragment length polymorphism (RFLP) along with parentage possibility.ConclusionsThe next-generation sequencing technology strives to deliver affordable and non-biased sequencing results, hence the complete genotyping formats of HNA may be reported collectively from mining the output data of WGS. The study shows the feasibility of HNA genotyping through new WGS technologies. Our proposed algorithmic methodology is implemented in a HNATyping software package with user’s guide available to the public at http://sourceforge.net/projects/hnatyping/.

Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study:

Background: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. Methods: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. Results: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. Conclusions: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.

Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments.

LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1β and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.