Dose- and time-dependent renoprotection of Angelica sinensis in patients with chronic kidney disease: A longitudinal cohort study.

Background: Based on their anti-oxidative and anti-fibrotic properties, Angelica sinensis (Oliv.) Diels roots [Apiaceae; Radix Angelicae sinensis] (Danggui [abbreviated as S in the context]), Astragalus membranaceus (Fisch.) Bunge [Fabaceae; Astragalus membranaceus] (Huangqi [A]), Rheum palmatum L. [Polygonaceae; Rheum palmatum] (Dahuang [R]), and Salvia miltiorrhiza Bunge [Lamiaceae; Salvia miltiorrhiza Bunge radix et rhizoma] (Danshen [D]) are potential renoprotective Chinese herbal medicines (CHMs). Renoprotection using ARD alone for the treatment of chronic kidney disease (CKD) has been documented in pre-clinical, clinical, and meta-analysis research; however, only pre-clinical data are available for the use of S alone. Moreover, with an increasing number of CKD patients taking prescribed CHMs, hyperkalemia risk remains unclear. Methods: This study retrospectively analyzed national health insurance claims data in 2001-2017. Propensity score matching was used to analyze renal and survival outcomes and the dose-response effects of S without ARD use in 18,348 new S users, 9,174 new ARD users, and 36,696 non-users. Cox proportional hazard regression was used to investigate adjusted hazard ratios (aHRs) for end-stage renal disease (ESRD) in the presence of competing mortality and death. The additive effect of the S herb in single form to compounds was also analyzed. Additionally, to analyze hyperkalemia risk, an exact match on each covariate was used to include 42,265 new CHM users and non-users, while Poisson regression was used to estimate adjusted incidence rate ratios (aIRRs) of hyperkalemia of prescribed CHMs. Results: S users and ARD users were associated with aHRs of 0.77 (95% confidence interval; 0.69-0.86) and 1.04 (0.91-1.19), respectively, for ESRD and 0.55 (0.53-0.57) and 0.71 (0.67-0.75), respectively, for death. The renal and survival benefits of S use were consistent in several sensitivity analyses. The dose- and time-dependent renoprotection and dose-dependent survival benefits were observed for S use. The top two additive renoprotective collocations of the S herb in compounds were Xue-Fu-Zhu-Yu-Tang and Shen-Tong-Zhu-Yu-Tang, followed by Shu-Jing-Huo-Xue-Tang and Shen-Tong-Zhu-Yu-Tang. Moreover, CHM users were associated with aIRRs of 0.34 (0.31-0.37) for hyperkalemia. Conclusion: This study suggests dose- and time-dependent renoprotection and dose-dependent survival benefits of the S herb in compounds and no increased hyperkalemia risk of the prescribed CHMs in CKD patients.

Long-term use of combined conventional medicine and Chinese herbal medicine decreases the mortality risk of patients with lung cancer.

BACKGROUND: We explored the effect of Chinese herbal medicine (CHM) on the long-term survival of lung cancer patients and hazard ratio (HR) and to analyse CHM herbs and formulas for lung cancer treatment. METHODS: We conducted a retrospective cohort study on diagnosed lung cancer patients in 2003-2016 from Taipei and Dalin Tzu Chi General Hospital Cancer Registry Database and from outpatient database from Chinese Medicine and Conventional Medicine Department. We categorised the patients into CHM user and CHM nonuser groups according to the CHM consumption time. After passing the proportional hazard assumption, we used the Cox PH model to calculate the groups' survival hazard ratio (HR) and examine the statistical difference and effect of CHM on lung cancer survival. RESULTS: We classified 2557 lung cancer patients into 1643 CHM nonusers and 228 CHM users. The CHM users had lower mortality than the CHM nonusers. With the multivariable Cox model, we observed that the CHM use was associated with 35% lower risk of mortality (adjusted HR: 0.65; 95% confidence interval: 0.51-0.76). Continuous CHM use of >180 days may further lessen the mortality risk by 64%. Finally, eight herbs and two formulas could significantly lower the mortality. After pairing the eight herbs for analysis, seven combinations could reduce the mortality better than only using one herb. CONCLUSION: CHM users had significantly lower mortality than CHM nonusers. The longer the CHM use, the more the mortality HR declined. Glehnia littoralisF. Schmidt ex Miq., Polyporus umbellatus(Pers.) Fries and Trichosanthes kirilowii Maxim. possess a highly substantial anticancer activity compared with other herbs.

Integrated Chinese Herbal Medicine and Western Medicine on the Survival in Patients with Colorectal Cancer: A Retrospective Study of Medical Records.

Recent studies suggested that Traditional Chinese Medicine could play a beneficial role in conventional cancer treatment. The aim of this retrospective cohort study was to investigate the effect of Chinese herbal medicine (CHM) combined with Western medicine on the survival of patients with colorectal cancer. A retrospective cohort study was conducted on patients with newly diagnosed colorectal cancer identified from the Dalin Tzu Chi Hospital Cancer Registry Database in 2004-2014. Combining with the medical records of the study hospital, patients were classified into CHM users and CHM nonusers. Kaplan-Meier analyses and Cox proportional hazards regression analyses were used to investigate the survival between CHM users and CHM nonusers. A total of 535 patients with colorectal cancer were included in the study with 147 of them were CHM users. The log-rank test for Kaplan-Meier survival curve revealed a statistically significant difference between the survival of CHM users and CHM nonusers (P=0.006). Results from multivariate Cox regression analysis showed that CHM use was significantly associated with better survival (adjusted hazard ratio = 0.54, 95% CI = 0.38 to 0.77). In addition, the CHM formulae Jia Wei Xiao Yao San, Zhi Bah Di Huang Wan, Ping Wei San, and Qui Pi Tang were significantly associated with better survival. In conclusion, findings from this retrospective cohort study indicated that integrated CHM and Western medicine could improve survival in patients with colorectal cancer. Additional research on integrating TCM with Western medicine to improve cancer survival is warranted.

Association of traditional Chinese medicine body constitution and moderate-to-severe cancer-related fatigue in cancer patients.

BACKGROUND AND PURPOSE: Fatigue is one of the most prevalent adverse events reported by cancer patients. The aim of this study was to investigate the association between traditional Chinese medicine body constitution (TCMBC) and moderate-to-severe cancer-related fatigue in cancer patients. MATERIALS AND METHODS: A cross-sectional study was conducted on cancer patients recruited from a regional hospital in southern Taiwan. The association between TCMBC, measured using the Constitution in Chinese Medicine Questionnaire (CCMQ) and moderate-to-severe cancer-related fatigue (based on the Taiwanese version of the Brief Fatigue Inventory score ≥ 4) was evaluated using multiple logistic regression analysis. RESULTS: Of the 170 participants, 37 (21.8%) had moderate-to-severe fatigue. Yang-deficiency (adjusted odds ratio [aOR] = 3.55, 95% confidence interval [CI] = 1.50-8.40) and Qi-deficiency (aOR = 2.84, 95% CI = 1.18-6.82) TCMBC were significantly associated with moderate-to-severe cancer-related fatigue. CONCLUSION: TCMBC could be used as a clinical tool to identify cancer patients prone to experience moderate-to-severe cancer-related fatigue, and to provide Chinese medicine practitioners a basis for selecting an appropriate treatment approach based on TCMBC.

Automated tongue diagnosis on the smartphone and its applications.

Tongue features are important objective basis for clinical diagnosis and treatment in both western medicine and Chinese medicine. The need for continuous monitoring of health conditions inspires us to develop an automatic tongue diagnosis system based on built-in sensors of smartphones. However, tongue images taken by smartphone are quite different in color due to various lighting conditions, and it consequently affects the diagnosis especially when we use the appearance of tongue fur to infer health conditions. In this paper, we captured paired tongue images with and without flash, and the color difference between the paired images is used to estimate the lighting condition based on the Support Vector Machine (SVM). The color correction matrices for three kinds of common lights (i.e., fluorescent, halogen and incandescent) are pre-trained by using a ColorChecker-based method, and the corresponding pre-trained matrix for the estimated lighting is then applied to eliminate the effect of color distortion. We further use tongue fur detection as an example to discuss the effect of different model parameters and ColorCheckers for training the tongue color correction matrix under different lighting conditions. Finally, in order to demonstrate the potential use of our proposed system, we recruited 246 patients over a period of 2.5 years from a local hospital in Taiwan and examined the correlations between the captured tongue features and alanine aminotransferase (ALT)/aspartate aminotransferase (AST), which are important bio-markers for liver diseases. We found that some tongue features have strong correlation with AST or ALT, which suggests the possible use of these tongue features captured on a smartphone to provide an early warning of liver diseases.

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.

Association of traditional Chinese medicine therapy and the risk of dementia in patients with hypertension: a nationwide population-based cohort study.

BACKGROUND: Patients with hypertension (HTN) reportedly have a higher risk of developing dementia. However, it remains unclear if use of Traditional Chinese Medicine (TCM), the most common form of complementary and alternative medicine, can help lower the risk of dementia for these patients. So the aim of the study was to investigate the effects of TCM on dementia risk among patients with hypertension. METHODS: This longitudinal cohort study used the Taiwanese National Health Insurance Research Database (NHIRD) to identify 143,382 newly diagnosed hypertension patients aged 20-90 years who received treatment between 1998 and 2007. Among them, 52,365 (36.52%) had received TCM after the onset of hypertension (TCM users), and the remaining 91,017 patients (63.48%) were designated as a control group (non-TCM users). All enrollees were followed until the end of 2012 to record the incidence of dementia. A Cox proportional hazards regression model was used to compute the hazard ratio (HR) of dementia in patients who received TCM. RESULTS: During the 15-year follow-up, 3933 TCM users and 10,316 non-TCM users developed dementia, representing an incidence rate of 8.41 and 11.55%, respectively, per 1000 person-years. TCM users had a significantly reduced risk of dementia compared to non-TCM users (adjusted HR = 0.76; 95% confidence interval [CI] = 0.74-0.81). The predominant effect was observed among those treated with TCM longer than 180 days (adjusted HR = 0.65; 95% CI = 0.62-0.69). Among the commonly used TCM products, Tian-Ma-Gou-Teng-Yin, Dan-Shen (Radix Salviae Miltiorrhizae), Chuan-Niu-Xi (Radix Cyathulae), Ge-Gen (Radix Puerariae), Jia-Wei-Xiao-Yao-San, and Jue-Ming-Zi (Semen Cassiae) were significantly associated with a lower risk of dementia. CONCLUSIONS: Results from this population-based study support the effects of TCM on reducing dementia risk, which may provide a reference for dementia prevention strategies.

Prescription patterns of Chinese herbal products for patients with fractures in Taiwan: A nationwide population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used in the treatment of fracture for thousands of years. However, large-scale surveys examing the utilization of Chinese herbal products (CHPs) for treating fractures and their related symptoms are lacking. This study aimed to investigate the prescription patterns of CHPs among patients with fractures in Taiwan. MATERIALS AND METHODS: The TCM usage in patients with fractures was analyzed using a sample of one million individuals randomly selected from the National Health Insurance Research Database who were newly diagnosis with fractures in 2001-2008, with a followed-up period through 2010. RESULTS: We identified 115,327 patients who were newly diagnosed with fractures in the study population. Among them, 4.97% (n=5731) adjunctively utilized TCM for fracture treatment. TCM users were mostly young or middle-aged, female, and resided in highly urbanized areas. With regard to the comorbidities of fractures, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus, hypertension and stroke than non-TCM users, except for osteoporosis. Shu-jing-huo-xue-tang was the most frequently prescribed Chinese herbal formula, while Rhizoma Drynariae (Gu-sui-bu) was the most common single herb for patients with fractures. The CHPs were found to cover not only bone healing but also fracture-related symptoms. TCM users had lower medical expenditure for hospitalization for the first six months after incident fractures than non-TCM users (1749±2650 versus 2274±3159 US dollars, p<0.0001). CONCLUSIONS: Our study identified the TCM utilization for patients with fractures in Taiwan. Integration of TCM treatment reduced the medical costs for hospitalization. Further basic research and clinical studies to investigate the mechanism and clinical efficacies of CHPs are warranted.

Gingyo-san enhances immunity and potentiates infectious bursal disease vaccination.

The purpose of the present study was to investigate the effects of Gingyo-san (GGS), a traditional Chinese medical formula, on peripheral lymphocyte proliferation and serum antibody titers in chickens vaccinated against the infectious bursal disease (IBD) virus. Treatment groups were fed one of three doses of GGS in their diet (0.5%, 1.0% and 2.0%, w/w), and the IBD vaccine was administered at 1 and 3 weeks of age. At Weeks 8, 12 and 16, changes in serum IBD antibody titers were measured via the micro-method and T cell proliferation. In gene expression experiments, GGS-treated peripheral T lymphocytes were stimulated with concanavalin A (ConA) for 24 h. The mRNA expression of interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-12 (IL-12) was determined using a semi-quantitative RT-PCR assay. The results showed that a low dose of GGS could significantly raise the antibody titers. Medium and high doses of GGS enhanced IL-2 and IFN-γ production. GGS altered the expression of IL-4 and IL-12 in T lymphocytes. CD4(+) T lymphocyte development was also skewed towards the Th1 phenotype. GGS enhanced cell-mediated immunity and augmented the effects of IBD vaccination in strengthening subsequent anti-viral responses.

The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factor-kappaB in human hepatocellular carcinoma cells.

Hesperidin (HES) has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. First, we suggest that the expression of MMP-9 by TPA involves phosphorylation of IKK, p38, and PKC in hepG2. We also demonstrate that hesperidin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells. Hesperidin significantly suppressed the TPA-induced the mRNA level of MMP-9. Hesperidin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF-kappaB) and Activator protein 1 (AP-1) activity. Hesperidin suppressed TPA-stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory signaling pathways and also inhibited TPA-induced AP-1 activity by the inhibitory phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling pathways. In conclusion, Hesperidin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-kappaB an AP-1 signaling pathway.

Porcine lactoferrin administration enhances peripheral lymphocyte proliferation and assists infectious bursal disease vaccination in native chickens.

The purpose of this study was to investigate the effects of dietary supplementation with recombinant porcine lactoferrin (rPLF) produced by yeast culture on peripheral lymphocyte proliferation and serum antibody titers in chickens vaccinated against the infectious bursal disease (IBD) virus. Treatment groups were fed with rPLF powder in their diet (2.0%, w/w), and the IBD vaccine was administrated at 1 and 3 weeks of age. At 8, 12, and 16 weeks after vaccination, serum IBD antibody titers were measured via the micro-method and T cell proliferation rates were evaluated. In gene expression analyses, rPLF-treated chicken peripheral T lymphocytes were stimulated with concanavalin A (ConA) for 24h. The mRNA expression levels of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and interleukin-12 (IL-12) were determined using a semi-quantitative RT-PCR assay. The results revealed that the rPLF additive led to significant increases in serum IgG and IBD-specific antibody titers (P<0.05). The rPLF administration significantly increased chicken intestinal villous lengths and also enhanced the expression of IFN-gamma and IL-12 in chicken T lymphocytes. These data suggest that rPLF enhances cell-mediated immunity and augment the ability of IBD vaccination to benefit chicken industry in disease resistance.

Xia-bai-san inhibits lipopolysaccharide-induced activation of intercellular adhesion molecule-1 and nuclear factor-kappa B in human lung cells.

UNLABELLED: Xia-bai-san (XBS) is a traditional Chinese medicine that has been used clinically for centuries in Asian countries to treat some types of common cold and asthma-like diseases similar to infantile pneumonia and childhood bronchitis. In previous studies, XBS was found to suppress the inflammatory process induced in lungs of mice treated with lipopolysaccharide (LPS). PURPOSE: The present study was undertaken to examine the effects of XBS on LPS-inducible production of inflammatory cytokines, up-regulation of intercellular cell adhesion molecule-1 (ICAM-1), and activation of nuclear factor NF-kappaB in cultured human lung cells. PRINCIPAL RESULTS: Extracts of four raw herbs (Cortex mori, Cortex lycii, Radix glycyrrhizae, and Fructus oryzae) were used to prepare the decoction. XBS decreased the histological damage and up-regulation of ICAM-1 observed in lungs of mice treated with lipopolysaccharide (LPS). In cultured human pulmonary epithelial A549 cells, XBS and its components Morus alba and Glycyrrhiza uralensis suppressed the up-regulation of IL-8 and ICAM-1 in response to LPS. Production of TNF-alpha, IL-1beta, IL-6 and IL-8 by LPS-treated human THP-1 monomyelocytes was also suppressed by XBS. A549 cells expressed ICAM-1 in response to medium from LPS-treated THP-1 cells; expression was decreased by XBS. The adhesion of THP-1 cells to LPS-treated A549 cells were inhibited in the presence of XBS. Activation of NF-kappaB by LPS in A549 cells was suppressed by XBS, Morus alba, and Glycyrrhiza uralensis through inhibition of IkappaB phosphorylation; the concentrations at which suppression occurred were identical to those at which production of inflammatory cytokines and up-regulation of ICAM-1 were inhibited. MAJOR CONCLUSIONS: These findings support the hypothesis that XBS, Morus alba, and Glycyrrhiza uralensis inhibit the inflammatory process in lung tissue through suppression of the IkappaB signaling pathway. XBS may prove helpful in the management of asthma, various allergic disorders, sepsis, or any other condition associated with pulmonary inflammation.

Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells.

Previous studies have revealed that acetaldehyde-induced cell invasion and matrix metalloproteinase-9 (MMP-9) activation and are directly involved in hepatic tumorigenesis and metastasis. Acetaldehyde is an important substance for tumor regression. We designed this study to aid in the development of powerful anti-cancer drugs with specific tumor regression and anti-metastatic potentials. Optimal drugs should possess both specific MMP-9 enzyme and gene transcriptional activities at the molecular level. Hesperidin, a flavonoid present in fruits and vegetables, possess anti-inflammatory and chemopreventive activities. Hesperidin suppressed acetaldehyde-induced cell invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells with acetaldehyde. Hesperidin suppressed acetaldehyde-induced MMP-9 expression through the inhibition of nuclear factor-kappaB (NF-kappaB) and AP-1, and suppressed acetaldehyde-stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory signaling pathways. Hesperidin also inhibited acetaldehyde-induced AP-1 activity by the inhibitory phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling pathways. Results from our study revealed that hesperidin suppressed both acetaldehyde-activated NF-kappaB and activator protein 1 (AP-1) activity by IkappaB, JNK, and p38 signaling pathways. This resulted in the reduction of MMP-9 expression, secretion, and hepatocarcinoma cellular invasion. Our result confirmed the therapeutic potential of hesperidin an anti-metastatic and its involvement in the acetaldehyde-induced cell invasiveness of hepatocellular carcinoma in alcoholic patients.

Protective and immunomodulatory effect of Gingyo-san in a murine model of acute lung inflammation.

To investigate the effects of Gingyo-san (GGS), the traditional Chinese medicinal formula, on the acute lung inflammation induced by LPS in vivo, mice were challenged with intratracheal LPS before treatment with GGS or vehicle. In lung morphology, GGS reduced the infiltration of activated polymorphonuclear neutrophils in the airways, decreased pulmonary edema, reduced nitrosative stress, and improved lung morphology. ELISA or RT-PCR detected the expression of cytokines in BALF and lung tissue. The mechanism of these benefits by treatment with GGS including attenuating expression TNFalpha, IL-1 beta, IL-6, KC, MCP-1, MIP-2, iNOS, and activation of nuclear factor (NF-kappaB and AP-1) in BALF and lung tissue. Particularly, GGS also enhanced the anti-inflammatory cytokine (IL-10) and limited the acute lung inflammation. Therefore, its protection activity against LPS-induced lung inflammatory mediators release might be beneficial in the treatment of endotoxin-associated inflammation.