Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management.

BACKGROUND: Type 2 diabetes mellitus (DM) is an independent risk factor for hepatocellular carcinoma (HCC), while insulin is a potent mitogen. Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers. AIM: To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control. METHODS: We used data acquired from the Taiwanese National Health Insurance research database between 2000 and 2017. We identified patients with DM who were prescribed insulin for > 3 months. The herb user group was further defined as patients prescribed herbal medication for DM for > 3 months per annum during follow-up. We matched the herb users to nonusers at a 1:3 ratio according to age, sex, comorbidities and index year by propensity score matching. We analyzed HCC incidence, HCC survival rates, and the herbal prescriptions involved. RESULTS: We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017. Among these, 46849 patients had used a herbal treatment for DM, and 140547 patients were included as the matched control group. The baseline variables were similar between the herb users and nonusers. DM patients with regular herb use had a 12% decreased risk of HCC compared with the control group [adjusted hazard ratio (aHR) = 0.88, 95%CI = 0.80-0.97]. The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers. Patients with a herb use of > 5 years cumulatively exhibited a protective effect against development of HCC (aHR = 0.82, P < 0.05). Of patients who developed HCC, herb users exhibited a longer survival time than nonusers (aHR = 0.78, P = 0.0001). Additionally, we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents. Our analysis indicated that Astragalus propinquus (Huang Qi) plus Salvia miltiorrhiza Bunge (Dan Shen), and Astragalus propinquus (Huang Qi) plus Trichosanthes kirilowii Maxim. (Tian Hua Fen) were the most frequent combination of single herbs. Meanwhile, Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas. CONCLUSION: This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12% in DM patients with regular insulin use.

Chinese Herbal Medicine Improved Survival in Stage IV Breast Cancer Patients: Data Mining of the Incorporated Taiwan Cancer Registry Database and Hospital Database.

BACKGROUND: According to recent research, breast cancer has become the most commonly diagnosed non-skin cancer type among the entire population. Meanwhile, Chinese herbal medicine (CHM) has become an important therapy to improve the survival rate and quality of life in metastatic cancer patients, as part of a wider trend toward more personalized medicine. However, there is a lack of research in terms of the association between stage IV breast cancer and CHM. Therefore, this study aimed to investigate the association between CHM and the survival rate in breast cancer patients at different cancer stages, with a particular focus on patients diagnosed with stage IV. METHODS: Patients with an initial diagnosis of breast cancer identified from the Taiwan Cancer Registry Database (TCRD) and China Medical University Hospital (CMUH) database were included in this study. Demographic characteristics including gender, age, and comorbidities were evaluated. Between-group differences for continuous and categorical variables were evaluated by the Student's t-test and Chi-square test, respectively. Patients diagnosed with breast cancer were recruited and divided into cohorts of CHM users and non-users with a 1:1 propensity score matching. The survival of breast cancer patients was assessed by the Cox proportional hazard model. The cumulative incidence of survival was assessed by Kaplan-Meier analysis. RESULTS: The adjuvant CHM treatment was associated with a higher survival rate in stage IV breast cancer patients (HR: 0.45, 95% CI: 0.2853-0.7044]. Additionally, the use of CHM had a positive impact on survival in stage IV breast cancer patients who had received surgery (P: .0273, HR: 0.3406, 95% CI: 0.1309-0.8865), chemotherapy (P: .0004, HR: 0.3893, 95% CI: 0.231-0.656), and hormone therapy (P: .0013, HR: 0.3491, 95% CI: 0.1836-0.6636). In terms of the specific CHM associated with survival, Zhi-Gan-Cao-Tang (ZGCT), Phellodendron chinense Schneid. (huang-bai), and Paeonia lactiflora Pall. (chi-shao) were the 3 most commonly prescribed herbal medicines correlated with a higher survival rate among stage IV breast cancer patients. CONCLUSIONS: CHM associated with conventional management achieved significant survival benefits in patients with stage IV breast cancer. Additional randomized controlled trials for prospective study are recommended for further validation.

Prescription system to calculate precise doses of Chinese herbal medicine to avoid toxic effects.

Background and objectives: Traditional Chinese Medicine (TCM) is a therapeutic system which has been practiced for thousands of years. Although for much of its history the decoction of medicinal herbs was the most common method of consuming the herbal treatments, TCM prescriptions are now primarily prepared using concentrated Chinese herbal extracts (CCHE) in powder or granular form. However, determining the precise dose of each single Chinese herbal constituent within a prescription creates a challenge in clinical practice due to the potential risk of toxicity. To alleviate this, we invented the Chinese Intelligence Prescription System (CIPS) to calculate the exact dose of each single herb within an individual prescription. Methods: In this study, we applied CIPS in a real-world setting to analyze clinical prescriptions collected and prepared at the TCM Pharmacy of China Medical University Hospital (CMUH). Results: Our investigation revealed that 3% of all prescriptions filled in a 1-month period contained inexact dosages, suggesting that more than 170,000 prescriptions filled in Taiwan in a given month may contain potentially toxic components. We further analyzed the data to determine the excess dosages and outline the possible associated side effects. Conclusions: In conclusion, CIPS offers TCM practitioners the ability to prepare exact Chinese herbal medicine (CHM) prescriptions in order to avoid toxic effects, thereby ensuring patient safety.

Chinese Intelligence Prescription System improves prescription accuracy while decreasing labor and drug costs.

BACKGROUND AND AIM: The traditional method of taking Chinese Medicine involves creating a decoction by cooking medicinal Chinese herbs. However, this method has become less popular, being replaced by the more convenient method of consuming concentrated Chinese herbal extracts, which creates challenges related to the complexity of stacking multiple formulas. METHODS: We developed the Chinese Intelligence Prescription System (CIPS) to simplify the prescription process. In this study, we used data from our institutions pharmacy to calculate the number of reductions, average dispensing time, and resulting cost savings. RESULTS: The mean number of prescriptions was reduced from 8.19 ± 3.65 to 7.37 ± 3.34 ([Formula: see text]). The reduction in the number of prescriptions directly resulted in decreased dispensing time, reducing it from 1.79 ± 0.25 to 1.63 ± 0.66 min ([Formula: see text]). The reduced dispensing time totaled 3.75 h per month per pharmacist, equivalent to an annual labor cost savings of $15,488 NTD per pharmacist. In addition, drug loss was reduced during the prescription process, with a mean savings of $4,517 NTD per year. The combined savings adds up to a not insignificant $20,005 NTD per year per pharmacist. When taking all TCM clinics/hospitals in Taiwan into account, the total annual savings would be $77 million NTD. CONCLUSION: CIPS assists clinicians and pharmacists to formulate precise prescriptions in a clinical setting to simplify the dispensing process while reducing medical resource waste and labor costs.

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.

Integrated Chinese herbal medicine and Western medicine successfully resolves spontaneous subcutaneous emphysema and pneumomediastinum in a patient with severe COVID-19 in Taiwan: A case report.

CASE: Serious complications of severe coronavirus disease 2019 (COVID-19) include subcutaneous emphysema (SE) and pneumomediastinum, which are complicated to treat with conventional Western medicine. We report how combining Chinese herbal medicine (CHM) with Western medicine quickly resolved a patient's COVID-19-associated pulmonary complications, shortened hospital stay and improved quality of life. CLINICAL FEATURES AND OUTCOME: A 59-year-old male with a history of smoking and tumors was diagnosed with COVID-19 in May 2021. At hospitalization, his oxygen saturation (SpO2) was 80%, he had a continuous severe cough, rapid shallow breathing, spontaneous SE and pneumomediastinum. By Day 4 of hospitalization, his condition was worsening despite standard care, so CHM was added. After 3-5 days, his coughing had lessened and supplementary oxygen therapy was de-escalated. Nine days after starting CHM, the SE had completely resolved and the patient avoided intubation. His WHO OS 10-point Scale score had fallen from 6 to 3 points and the modified Medical Research Council Dyspnea Scale score from 4 to 2 points. He was hospitalized for 19 days. At 1 week post-discharge, the patient could handle most of his daily activities and experienced minor shortness of breath only when performing labor-intensive tasks. At 1 month, his work output was restored to pre-COVID-19 levels. CONCLUSION: CHM combined with standard Western medicine improved pulmonary function, respiratory rate, blood oxygen saturation and shortened the hospital stay of a patient with severe COVID-19 complicated by SE and pneumomediastinum.

Concurrent use of Chinese herbal medicine and anticoagulants may reduce major bleeding events.

BACKGROUND: This retrospective cohort study investigated the risk of major bleeding events during the concurrent use of Chinese herbal medicine (CHM) and anticoagulants in clinical practice. METHODS: A total of 4,470 patients receiving anticoagulant drugs were selected from Taiwan's National Health Insurance Research Database (NHIRD). Half (n = 2,235) were also using CHMs (CHM cohort); the other half were not (non-CHM cohort). Each cohort was matched 1:1 using the propensity score. Chi-square testing and the Student's t-test were used to examine differences between two cohorts. Cox proportional hazard regression analysis assessed the risks for major bleeding events in each cohort, as well as bleeding risks associated with specific CHM formulas and herbs. Cumulative incidence curves for major bleeding events were calculated using Kaplan-Meier analysis. RESULTS: Compared with the non-CHM cohort, the CHM cohort had a lower risk of overall bleeding events (p < 0.001) including hemorrhagic stroke (p = 0.008), gastrointestinal (GI) bleeding (p < 0.001), urogenital bleeding (p ≤ 0.001) and nasal/ear/eye bleeding (p = 0.004). Single herbs, such as Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum, Eucommia ulmoides Oliver and formulas, such as Shu Jing Huo Xue Tang, Shao Yao Gan Cao Tang and Ji Sheng Shen Qi Wan were associated with a lower risk of major bleeding events. CONCLUSION: Using CHMs with anticoagulants appeared to decrease the risk of major bleeding, especially CHMs products containing Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum and Eucommia ulmoides Oliver. Further investigations are needed to determine whether CHM can maintain the therapeutic efficacy of anticoagulants while simultaneously reducing potential side effects.

Effects of Chinese herbal medicine in patients with benign prostatic hyperplasia: A nationwide cohort study in Taiwan.

OBJECTIVES: Benign prostatic hyperplasia affects elderly males, with progression presenting the risk of urinary complications and eventual surgical intervention. We aimed to evaluate the effects of Chinese herbal medicine in patients with benign prostatic hyperplasia. METHODS: This retrospective cohort study analyzed claims data in Taiwan's National Health Insurance Research Database from 2001 to 2013. A total of 4142 patients newly diagnosed as benign prostatic hyperplasia were enrolled and divided into cohorts of Chinese herbal medicine users and nonusers by performing 1:1 propensity score matching. The risk of benign prostatic hyperplasia-related complications was assessed by the Cox proportional hazard model. The cumulative incidence of benign prostatic hyperplasia-related surgeries was assessed by Kaplan-Meier method. RESULTS: During the study period, the risk of benign prostatic hyperplasia-related complications was lower in the Chinese herbal medicine cohort than non-Chinese herbal medicine cohort with an adjusted hazard ratio of 0.82 (95% confidence interval 0.73-0.92) after controlling for multiple variables. Subgroup analysis revealed that Chinese herbal medicine users had a significantly lower risk of urinary tract infection (adjusted hazard ratio 0.67, 95% confidence interval 0.50-0.89) and urinary retention (adjusted hazard ratio 0.83, 95% confidence interval 0.72-0.97). In addition, Chinese herbal medicine users also had a lower incidence rate of benign prostatic hyperplasia-related surgery (32.14 vs 40.20, adjusted hazard ratio 0.74, 95% confidence interval 0.61-0.89) and a longer surgery-free interval than non-Chinese herbal medicine users (3.98 vs 3.00 mean person-year, P < 0.001). Data revealed Salviae miltiorrhizae and Ji-Sheng-Shen-Qi-Wan as the most commonly prescribed Chinese herbal medicine by traditional Chinese medicine practitioners. CONCLUSIONS: Our study demonstrated that Chinese herbal medicine might have effects in the benign prostatic hyperplasia-related complications and surgeries in patients with benign prostatic hyperplasia.

Associations of Chinese Herbal Medicine Use with the Risks of Acute Exacerbation and Mortality in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Objectives: This study aimed to assess the correlation of exacerbation and the mortality rate in patients with chronic obstructive pulmonary disease (COPD) between biomedical treatments with or without Chinese herbal medicine (CHM) as an adjunct. Design: A total of 81,261 COPD patients were identified from the National Health Insurance Research Database in Taiwan between 2001 and 2012. After screening and matching, 3176 COPD patients were included in the study. Statistical analyses were performed to assess the differences in the baseline characteristics. The authors used the Cox proportional hazard regression analysis to calculate the risks of mortality and hospitalization due to acute exacerbation of COPD within 1 year between a CHM user cohort and non-CHM user cohort. The cumulative incidence of mortality in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. Results: COPD patients in the CHM user cohort demonstrated a significantly lower risk of mortality (p < 0.001) and acute exacerbation (p < 0.05), compared with the non-CHM user cohort. In addition, the CHM users exhibited a reduced cumulative incidence of mortality compared with the non-CHM user cohort (p < 0.001). Xiao Qing Long Tang and Fritillariae thunbergii were the most common Chinese herbal formula and single Chinese herb prescribed for COPD patients. Conclusion: Combining CHM with biomedical treatment might reduce the risk of acute exacerbation and incidence of mortality in patients with COPD.

Scutellaria barbata D. Don Inhibits the Main Proteases (Mpro and TMPRSS2) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged to severely impact the global population, creating an unprecedented need for effective treatments. This study aims to investigate the potential of Scutellaria barbata D. Don (SB) as a treatment for SARS-CoV-2 infection through the inhibition of the proteases playing important functions in the infection by SARS-CoV-2. FRET assay was applied to investigate the inhibitory effects of SB on the two proteases involved in SARS-CoV-2 infection, Mpro and TMPRSS2. Additionally, to measure the potential effectiveness of SB treatment on infection inhibition, cellular models based on the Calu3 and VeroE6 cells and their TMPRSS2- expressing derivatives were assessed by viral pseudoparticles (Vpp) infection assays. The experimental approaches were conjugated with LC/MS analyses of the aqueous extracts of SB to identify the major constituent compounds, followed by a literature review to determine the potential active components of the inhibitory effects on protease activities. Our results showed that SB extracts inhibited the enzyme activities of Mpro and TMPRSS2. Furthermore, SB extracts effectively inhibited SARS-CoV-2 Vpp infection through a TMPRSS2-dependent mechanism. The aqueous extract analysis identified six major constituent compounds present in SB. Some of them have been known associated with inhibitory activities of TMPRSS2 or Mpro. Thus, SB may effectively prevent SARS-CoV-2 infection and replication through inhibiting Mpro and TMPRSS2 protease activities.

Successful intervention with Chinese herbal medicine for hyperthyroidism: Two case reports and a literature review.

BACKGROUND: Hyperthyroidism, the excessive production of thyroid hormones, is most commonly attributed to autoimmune dysfunction such as Graves' disease. Western medical treatment of hyperthyroidism includes antithyroid medications, radioiodine, and thyroidectomy, all of which are associated with side effects. We describe the successful treatment of two patients with Graves' disease who used Chinese herbal medicine (CHM) with or without Western medicine. CASE PRESENTATION: Both cases (a 50-year-old female [case 1] and a 56-year-old male [case 2]) received the Chinese herbal formula Jia Wei Xiao Yao San (JWXYS) as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas. Elevated thyroid hormone levels were restored to normal after 10 months of treatment in case 1 and 8 months in case 2. Neither patient experienced any complications or side effects during CHM treatment. Notably, symptoms and thyroid hormone levels have remained well controlled in both patients over 1 year of follow-up until the time of this report. To explore the possible mechanisms involved in CHM treatment of hyperthyroidism, we searched biomedical literature databases and reviewed the literature up to June 2020. CONCLUSIONS: As for the hyperthyroidism almost was controlled by Western medicine instead of CHM, we report that JWXYS as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas was a safe and effective formula and we propose that CHM may be considered as either a first choice or combination therapy to control hyperthyroidism.

Principles and treatment strategies for the use of Chinese herbal medicine in patients at different stages of coronavirus infection.

Coronavirus disease 2019 (COVID-19) is a novel, human-infecting ß-coronavirus enveloped, positive-sense single-stranded RNA viruses, similar to the severe acute respiratory syndrome (SARS) infection that emerged in November 2002. In traditional Chinese medicine (TCM), the epidemic disease concepts of "febrile epidemics" (wenyi) or "warm diseases" (wenbing) are based on geographic and cultural aspects, and Chinese herbal medicine (CHM) played an important role in the treatment of epidemic diseases. CHM was widely used to treat patients suffered with SARS almost two decades ago during outbreak of SARS, with proven safety and potential benefits. TCM has also been widely used to treat cancer patients for a long history and much of them associate with immunomodulatory activity and are used to treat coronavirus-related diseases. We propose the use of CHM treatment principles for clinical practice, based on four main stages of COVID-19 infection: early, intermediate, severe, and convalescence. We suggest corresponding decoctions that exhibit antiviral activity and anti-inflammatory effects in the early stage of infection; preventing the disease from progressing from an intermediate to severe stage of infection; restoring normal lung function and improving consciousness in the severe stage; and ameliorating pulmonary and vascular injury in the convalescent stage. We summarize the pharmaceutical mechanisms of CHM for treating coronavirus via antiviral, anti-inflammatory and immunomodulatory effects.

Application of Neural Network and Cluster Analyses to Differentiate TCM Patterns in Patients With Breast Cancer.

BACKGROUND AND PURPOSE: Pattern differentiation is a critical element of the prescription process for Traditional Chinese Medicine (TCM) practitioners. Application of advanced machine learning techniques will enhance the effectiveness of TCM in clinical practice. The aim of this study is to explore the relationships between clinical features and TCM patterns in breast cancer patients. METHODS: The dataset of breast cancer patients receiving TCM treatment was recruited from a single medical center. We utilized a neural network model to standardize terminologies and address TCM pattern differentiation in breast cancer cases. Cluster analysis was applied to classify the clinical features in the breast cancer patient dataset. To evaluate the performance of the proposed method, we further compared the TCM patterns to therapeutic principles of Chinese herbal medication in Taiwan. RESULTS: A total of 2,738 breast cancer cases were recruited and standardized. They were divided into 5 groups according to clinical features via cluster analysis. The pattern differentiation model revealed that liver-gallbladder dampness-heat was the primary TCM pattern identified in patients. The main therapeutic goals of the top 10 Chinese herbal medicines prescribed for breast cancer patients were to clear heat, drain dampness, and detoxify. These results demonstrated that the neural network successfully identified patterns from a dataset similar to the prescriptions of TCM clinical practitioners. CONCLUSION: This is the first study using machine-learning methodology to standardize and analyze TCM electronic medical records. The patterns revealed by the analyses were highly correlated with the therapeutic principles of TCM practitioners. Machine learning technology could assist TCM practitioners to comprehensively differentiate patterns and identify effective Chinese herbal medicine treatments in clinical practice.

Chinese herbal medicine reduces the risk of urinary incontinence in patients with chronic obstructive pulmonary disease: A population-based retrospective cohort study.

OBJECTIVES: To investigate the effectiveness of Chinese herbal medicine for the treatment of urinary incontinence in patients with chronic obstructive pulmonary disease. METHODS: We carried out a retrospective cohort study using the National Health Insurance Research Database. From a cohort of 1 million records between 1996 and 2013, a total of 202 279 patients with newly onset chronic obstructive pulmonary disease were initially recruited. We matched with propensity score 3967 patients who received Chinese herbal medicine by age, sex, year of chronic obstructive pulmonary disease diagnosis, urbanization, comorbidities and chronic obstructive pulmonary disease medications. All participants received follow-up visits until the end of 2013 to record the incidence rate of urinary incontinence. The Cox proportional hazards model was applied to assess the association between Chinese herbal medicine use and the risk of urinary incontinence among chronic obstructive pulmonary disease patients. RESULTS: The incidence rates of urinary incontinence were 57.33 and 108.15 (per 10 000 person-years) in the Chinese herbal medicine and non-Chinese herbal medicine cohorts, respectively, showing a significantly lower risk of urinary incontinence in Chinese herbal medicine users (aHR = 0.56, 95% CI = 0.45-0.69, P < 0.001). The Chinese herbal medicine prescription pattern analysis showed that Fritillariae thunbergii bulbus (Zhebeimu), Semen armeniacae amarum (Kuxingren), Platycodonis radix (Jiegeng), Xiao Qing Long Tang and Ding Chuan Tang constituted the core of Chinese herbal medicine prescriptions applied to treat chronic obstructive pulmonary disease. CONCLUSION: The use of Chinese herbal medicine in chronic obstructive pulmonary disease patients can reduce their risk of urinary incontinence.

Integrating Chinese and Western medicines reduced the incidence of hepatocellular carcinoma in patients with diabetes mellitus: A Taiwanese population-based cohort study.

OBJECTIVES: Much epidemiological evidence links diabetes mellitus (DM) to the development of multiple cancers and, in particular, the development of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether Chinese herbal medicine (CHM) reduces the incidence of HCC in patients receiving Western antidiabetic drugs. INTERVENTIONS AND MAIN OUTCOME MEASURES: This retrospective cohort study used data from the National Health Insurance Research Database involving 81,105 diabetic patients, including 5122 CHM users and 25,966 non-CHM users. Analyses of treatment effects were adjusted for covariates including gender, age, comorbidities, antidiabetic drugs and liver medications. NodeXL software performed a network analysis to identify the 50 most commonly used CHM herbs and formulas. RESULTS: In Cox proportional hazards models adjusted for demographic and clinical characteristics, DM patients exposed to adjuvant CHM therapy were significantly less likely to develop HCC compared with non-CHM users (adjusted hazard ratio [aHR] 0.59; 95 % confidence interval [CI], 0.41-0.87; p = 0.01). Kaplan-Meier analysis revealed a lower 10-year cumulative risk of HCC among CHM users compared with non-CHM users. Amongst the 10 individual CHM herbs and herbal formulas most commonly prescribed for DM, the most frequent were Salvia miltiorrhiza (Dan Shen) and Liu Wei Di Huang Wan, respectively. CONCLUSION: This nationwide retrospective cohort study from Taiwan provides some valuable insights into the prescribing characteristics of CHM treatment in patients with DM. Compared with use of Western antidiabetic medications alone, use of adjuvant CHM effectively reduces the incidence of HCC in patients with DM.

Effect of Chinese Herbal Medicine Therapy on Overall and Cancer Related Mortality in Patients With Advanced Nasopharyngeal Carcinoma in Taiwan.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer involving epithelial squamous-cell carcinoma of the nasopharynx that mainly occurs in individuals from East and Southeast Asia. We investigated whether Chinese herbal medicine (CHM) as a complementary therapy offers benefits to these patients. We retrospectively evaluated the Taiwan Cancer Registry (Long Form) database for patients with advanced NPC, using or not using CHM, between 2007-2013. Cox proportional-hazard model and Kaplan‒Meier survival analyses were applied for patient survival. CHM-users showed a lower overall and cancer-related mortality risk than non-users. For advanced NPC patients, the overall mortality risk was 0.799-fold for CHM-users, after controlling for age, gender, and Charlson comorbidity index (CCI) score (Cancer stages 3 + 4: adjusted hazard ratio [aHR]: 0.799, 95% confidence interval [CI]: 0.676-0.943, p = 0.008). CHM-users also showed a lower cancer-related mortality risk than non-users (aHR: 0.71, 95% CI: 0.53-0.96, p = 0.0273). Association rule analysis showed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D.Don) and For single herbs, Bai-Hua-She-She-Cao (Herba Hedyotis Diffusae; Scleromitrion diffusum (Willd.) R.J.Wang (syn. Hedyotis diffusa Willd.) and Mai-Men-Dong (MMD; Ophiopogon japonicus (Thunb.) Ker Gawl.), and Gan-Lu-Yin (GLY) and BHSSC. Network analysis revealed that BHSSC was the core CHM, and BZL, GLY, and Xin-Yi-Qing-Fei-Tang (XYQFT) were important CHMs in cluster 1. In cluster 2, ShengDH, MMD, Xuan-Shen (XS; Scrophularia ningpoensis Hensl.), and Gua-Lou-Gen (GLG; Trichosanthes kirilowii Maxim.) were important CHMs. Thus, as a complementary therapy, CHM, and particularly the 8 CHMs identified, are important for the treatment of advanced NPC patients.

Chinese Herbal Medicine Ameliorated the Development of Chronic Kidney Disease in Patients with Chronic Hepatitis C: A Retrospective Population-Based Cohort Study.

Chronic kidney disease (CKD) is a serious complication affecting patients with chronic hepatitis. The effectiveness of CHM for the prevention of CKD in hepatitis patients remains unclear. Therefore, we conducted a retrospective cohort study to investigate the effectiveness of CHM in preventing the development of CKD in hepatitis patients. From a subdataset of the Taiwan National Health Insurance Research Database (NHIRD), we included 19,409 patients newly diagnosed with hepatitis B and hepatitis C between the years 2000 and 2010. After exclusion criteria and 1 : 1 propensity score matching process, we compared demographic factors, comorbidities, and correlated drugs between the CHM and non-CHM cohorts. Statistical analysis was applied to evaluate the differences in characteristic distributions and to compare the cumulative incidence of CKD between the CHM and non-CHM cohorts. This study showed that the patients suffering from hepatitis C with CHM treatment more than 90 days as an adjuvant therapy combined with western medical treatment modalities exhibited a decreased risk of developing CKD (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.21-0.76, p value <0.01). The Kaplan-Meier curve revealed a lower cumulative incidence rate of CKD (p value = 0.004) for the CHM cohort. For further reference, we herein offer the ten most frequently prescribed single herbs and herbal formulas; as such, Salviae miltiorrhizae and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and formula, respectively. This nationwide retrospective cohort study provides evidence that CHM is an effective adjuvant treatment to decrease the risk of developing CKD in hepatitis C patients.

Conventional Western Treatment Combined With Chinese Herbal Medicine Alleviates the Progressive Risk of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Background and purpose: Lung cancer has high global incidence and mortality rates. Chronic obstructive pulmonary disease (COPD) is strongly associated with lung cancer and is an independent risk factor for lung cancer with or without smoking. Chinese herbal medicines (CHMs) are used to treat COPD. This study sought to determine whether CHM treatment effectively decreases the incidence of lung cancer in COPD patients receiving conventional Western medical treatment. Methods: Records obtained from the National Health Insurance Research Database (NHIRD) were used to identify 81,780 adults aged ≥18 years newly diagnosed with COPD in Taiwan between 2000 and 2010. Among them, 11,180 received CHMs after COPD diagnosis and 23,319 did not (non-CHM). After excluding patients with missing basic demographic information, each group consisted of 2,682 patients. Statistical methods analyzed the baseline characteristics for both groups and we performed a Cox proportional hazard regression analysis to examine the incidence of lung cancer. The cumulative incidence of lung cancer in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. The association between herbs and formulas was examined by NodeXL to perform a network analysis of CHM. Results: COPD patients using CHM had a lower risk for lung cancer (adjusted hazards ratio [aHR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, p < 0.001). Older age was associated with a higher risk of lung cancer: patients aged 40-59 years (aHR = 5.32, 95% CI = 2.19-12.94, p < 0.001) and those aged ≥60 years (aHR = 16.75, 95% CI = 7.54-37.23, p < 0.001) were at significantly greater risk compared with patients aged 18-39 years. CHM use was associated with a trend for a lower cumulative incidence of lung cancer compared with non-CHM use (p < 0.001). Among the 10 most commonly used single herbs and formulas used to decrease the risk of lung cancer in COPD patients, Fritillariae thunbergii was the most commonly used single herb and Xiao Qing Long Tang the most commonly used formula. Conclusion: The findings from this nationwide retrospective cohort study indicate that CHM as adjunctive therapy in COPD treatment regimens may reduce the risk of lung cancer in this vulnerable patient population.

Chinese Herbal Medicine Ganoderma tsugae Displays Potential Anti-Cancer Efficacy on Metastatic Prostate Cancer Cells.

Resistance to the current therapies is the main clinical challenge in the treatment of lethal metastatic prostate cancer (mPCa). Developing novel therapeutic approaches with effective regimes and minimal side effects for this fatal disease remain a priority in prostate cancer study. In the present study, we demonstrated that a traditional Chinese medicine, quality-assured Ganoderma tsugae ethanol extract (GTEE), significantly suppressed cell growth and metastatic capability and caused cell cycle arrest through decreasing expression of cyclins in mPCa cells, PC-3 and DU145 cells. GTEE also induced caspase-dependent apoptosis in mPCa cells. We further showed the potent therapeutic efficacy of GTEE by inhibiting subcutaneous PC-3 tumor growth in a xenograft model. The in vitro and in vivo efficacies on mPCa cells were due to blockade of the PI3K/Akt and MAPK/ERK signaling pathways associated with cancer cell growth, survival and apoptosis. These preclinical data provide the molecular basis for a new potential therapeutic approach toward the treatment of lethal prostate cancer progression.

Mitochondrial Transfer of Wharton's Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts.

Wharton's jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene. The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions. In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts. By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated. After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention. Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs. Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance. This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer. This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.