Recommendations and guidelines of integrative medicine for COVID-19 care: The APEC project outcome.

This article - Recommendations and Guidelines of Integrative Medicine (IM) for COVID-19 Care - was one of the outcomes from an Asia-Pacific Economic Cooperation (APEC) Project (Integrative Medicine (IM) and COVID -19 Care) during the time between May 2022 and March 2023. With the efforts from care providers, researchers, health policy makers and healthcare administrative leaders among APEC economies, the purpose of this file was to provide comprehensive IM systems for COVID-19 care as recommendations and suggestive guidelines including care methods, tools, procedures, symptom conditions and targets selections, and points need to be considered during care applications. All cited COVID-19 care practices have confirmed their efficacy and usefulness either used alone or combined with conventional medicine. This article provides current useful medical information on IM for COVID-19 care which could benefit APEC economies and world health communities on their healthcare system.

Traditional Chinese medicine in the treatment of patients with hyperuricemia: A randomized placebo-controlled double-blinded clinical trial.

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.

Association between traditional Chinese medicine body constitution deviation and chronic pelvic pain: A cross-sectional study.

OBJECTIVE: Chronic pelvic pain (CPP) is one of the most challenging conditions that physicians and patients face nowadays. This study aimed to assess the traditional Chinese medicine (TCM) body constitution profiles, demographic characteristics, and lifestyle of women suffering from CPP. MATERIALS AND METHODS: This study included 378 female patients of reproductive potential from a single Obstetrics and Gynecology clinic in Taiwan. Data were collected using the Short Form 36 Health Survey Questionnaire (SF-36), the TCM Body Constitution Deviation (BCQ-44) Questionnaire, and the Behavior Rating Scale. The chi-squared test, the Kruskal-Wallis test, the Mann-Whitney U test, and Spearman's correlation were used to analyze the data. RESULTS: TCM body composition deviation was correlated with the level of pain in patients with CPP. Moreover, the quality of life (QOL) of these patients was found to be affected by the level of pain. Additionally, the QOL was correlated with the TCM body composition deviation profile. CONCLUSION: The TCM BCQ-44 can be used in the medical practice to assess patients' health status and can also serve as a guide to address the risk factors for CPP.

NRICM101 ameliorates SARS-CoV-2-S1-induced pulmonary injury in K18-hACE2 mice model.

The coronavirus disease 2019 (COVID-19) pandemic continues to represent a challenge for public health globally since transmission of different variants of the virus does not seem to be effectively affected by the current treatments and vaccines. During COVID-19 the outbreak in Taiwan, the patients with mild symptoms were improved after the treatment with NRICM101, a traditional Chinese medicine formula developed by our institute. Here, we investigated the effect and mechanism of action of NRICM101 on improval of COVID-19-induced pulmonary injury using S1 subunit of the SARS-CoV-2 spike protein-induced diffuse alveolar damage (DAD) of hACE2 transgenic mice. The S1 protein induced significant pulmonary injury with the hallmarks of DAD (strong exudation, interstitial and intra-alveolar edema, hyaline membranes, abnormal pneumocyte apoptosis, strong leukocyte infiltration, and cytokine production). NRICM101 effectively reduced all of these hallmarks. We then used next-generation sequencing assays to identify 193 genes that were differentially expressed in the S1+NRICM101 group. Of these, three (Ddit4, Ikbke, Tnfaip3) were significantly represented in the top 30 enriched downregulated gene ontology (GO) terms in the S1+NRICM101 group versus the S1+saline group. These terms included the innate immune response, pattern recognition receptor (PRR), and Toll-like receptor signaling pathways. We found that NRICM101 disrupted the interaction of the spike protein of various SARS-CoV-2 variants with the human ACE2 receptor. It also suppressed the expression of cytokines IL-1ß, IL-6, TNF-α, MIP-1ß, IP-10, and MIP-1α in alveolar macrophages activated by lipopolysaccharide. We conclude that NRICM101 effectively protects against SARS-CoV-2-S1-induced pulmonary injury via modulation of the innate immune response, pattern recognition receptor, and Toll-like receptor signaling pathways to ameliorate DAD.

Preoperative Use and Discontinuation of Traditional Chinese Herbal Medicine and Dietary Supplements in Taiwan: A Cross-Sectional Questionnaire Survey.

Traditional Chinese herbal medicine has widespread use in Taiwan. This cross-sectional questionnaire survey investigates the preoperative use and discontinuation of Chinese herbal medicine and dietary supplements among Taiwanese patients. We obtained the types, frequency, and sources of Chinese herbal remedies and supplements used. Among 1428 presurgical patients, 727 (50.9%) and 977 (68.4%) reported the use of traditional Chinese herbal medicine and supplements in the past one month, respectively. Only 17.5% of the 727 patients stated discontinuation of herbal remedies 4.7 ± 5.1 (1-24) days before the surgery, and 36.2% took traditional Chinese herbal medicine with concomitant physician-prescribed Western medicine for their underlying diseases. The most commonly used Chinese herbs are goji berry (Lycium barbarum) (62.9%) and Si-Shen-Tang (48.1%) in single and compound forms, respectively. The presurgical use of traditional Chinese herbal medicine was common in patients undergoing gynecologic (68.6%) surgery or diagnosed with asthma (60.8%). Women and those with a high household income had a greater tendency to use herbal remedies. This study demonstrates the high proportion of the presurgical use of Chinese herbal remedies and supplements along with physician-prescribed Western medicine in Taiwan. Surgeons and anesthesiologists should be aware of the potential adverse effects of drug-herb interaction for Chinese patients.

Efficacy analysis and research progress of complementary and alternative medicines in the adjuvant treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan.

Associations of traditional Chinese medicine body constitution and all-cause mortality in patients with type 2 diabetes mellitus: a prospective cohort study of a Taiwanese medical center.

Introduction: The objective of this study was to investigate associations between baseline body constitutions (BCs) in traditional Chinese Medicine (TCM) and all-cause mortality in Chinese individuals with type 2 diabetes. Methods: A total of 887 individuals with type 2 diabetes who were enrolled in managed care in 2010 were included. These individuals were followed up until 2015, and their mortality status was determined through the use of Taiwan National Death Datasets. At baseline, BC status of participants, including Yin deficiency, Yang deficiency, and phlegm stasis, was assessed using a well-developed Body Constitutions Questionnaire. Hazard ratios (HR) were calculated using a multivariate Cox proportional hazards model. Results: During 6807.2 person-years of follow-up of 887 participants, with an average follow-up period of 7.7 years, a total of 190 individuals died, resulting in an incidence density of 0.0279 person-years. Yin deficiency was associated with all-cause mortality (HR, 95% CI: 1.39, 1.02-1.90). This study indicates that individuals diagnosed with Yin deficiency in TCM, characterized by symptoms such as thirst, reduced urine volume, hard stool, and hot flushes, had a 39% higher risk of all-cause mortality. Discussion: The findings may provide information for TCM practitioners on tailoring treatment plans for persons with type 2 diabetes. No conclusive statements can be made on the basis of the preliminary data presented here. Controlled prospective studies are warranted.

Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study.

This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05-4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03-4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.

Levonorgestrel intrauterine devices improve body constitution deviations in the perspective of traditional Chinese medicine and quality of life in patients with chronic pelvic pain and heavy menstrual bleeding.

OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Chinese herbal prescriptions for COVID-19 management: Special reference to Taiwan Chingguan Yihau (NRICM101).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. As at June 2022, increasing numbers of newly diagnosed COVID-19-associated pneumonia cases worldwide have attracted close attention from the international community. The present review analyzes and summarizes the treatment of COVID-19 with traditional Chinese medicine (TCM). A systematic analysis of the efficacies and benefits of TCM for the treatment of COVID-19 was performed, and the mechanisms underlying such treatment are summarized. This analysis of the literature highlights the potential of TCM to prevent and treat COVID-19 via antiviral, anti-inflammatory and immunomodulatory activities, with evidence showing that many TCM components act upon multiple targets and pathways. Famous TCM formulas include Qing-Fei-Pai-Du-Tang (QFPDT), Lianhuaqingwen Capsule (LHC), Taiwan Chingguan Yihau (NRICM101), and Jing Si herbal drink (JSHD). In particular, the botanical preparation NRICM101 was developed in 2020 for use in viral respiratory tract infections and is recommended for treating non-severe and mild COVID-19 infections. NRICM101 has been adopted for use in Taiwan for the clinical treatment of COVID-19. The common components and active ingredients of 10 TCM preparations have been analyzed for the most promising substances. This review aims to provide reliable evidence demonstrating the therapeutic efficacy of TCM substances in support of their further development against novel coronavirus infectious diseases in Taiwan.

Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis.

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-1ß, 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.

Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

A traditional Chinese medicine formula NRICM101 to target COVID-19 through multiple pathways: A bedside-to-bench study.

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.

Taipei consensus on integrative traditional Chinese and Western Medicine.

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.

Disclosure of suboptimal health status through traditional Chinese medicine-based body constitution and pulse patterns.

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 < 0.001), but weak correlations were discovered for healthy participants. The participants with SHS had significantly higher SER10 at the left guan (the "liver" system in TCM) than did the healthy participants. CONCLUSIONS: SHS is moderately correlated with TCM-based constitution and those with SHS had increased SER10 at the leftguan of the radial pulse.

Using Chinese Body Constitution Concepts and Measurable Variables for Assessing Risk of Coronary Artery Disease.

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.