Assessment of palmitic acid toxicity to animal hearts and other major organs based on acute toxicity, network pharmacology, and molecular docking.

Palmitic acid is a common ingredient in many foods and traditional Chinese medicines. However, modern pharmacological experiments have shown that palmitic acid has toxic side effects. It can damage glomeruli, cardiomyocytes, and hepatocytes, as well as promote the growth of lung cancer cells. Despite this, there are few reports evaluating the safety of palmitic acid through animal experiments, and the mechanism of palmitic acid toxicity remains unclear. Clarifying the adverse reactions and mechanisms of palmitic acid in animal hearts and other major organs is of great significance for ensuring the safety of clinical application. Therefore, this study records an acute toxicity experiment on palmitic acid in a mouse model, and the observation of pathological changes in the heart, liver, lungs, and kidneys. It is found that palmitic acid had toxic and side effects on animal heart. Then the key targets of palmitic acid in regulating cardiac toxicity were screened using network pharmacology, and a "component-target-cardiotoxicity" network diagram and PPI network were constructed. The mechanisms regulating cardiotoxicity were explored using KEGG signal pathway and GO biological process enrichment analyses. Molecular docking models were used for verification. The results showed that the maximum dose of palmitic acid had low toxicity in the hearts of mice. The mechanism of cardiotoxicity of palmitic acid involves multiple targets, biological processes, and signaling pathways. Palmitic acid can induce steatosis in hepatocytes, and regulate cancer cells. This study preliminarily evaluated the safety of palmitic acid and provided a scientific basis for its safe application.

Efficacy and safety assessment of traditional Chinese medicine for erectile dysfunction: A meta-analysis and trial sequential analysis.

BACKGROUND: Several patients with erectile dysfunction do not accept or benefit from conventional therapy with phosphodiesterase type 5 inhibitors; thus, alternative and complementary therapies are in need. Traditional Chinese medicine has been treating erectile dysfunction in China, but its clinical value is inconclusive. OBJECTIVE: To systematically evaluate the efficacy and safety of traditional Chinese medicine in treating erectile dysfunction. METHODS: Randomized controlled trials were retrieved from a comprehensive search in the literature published in the past decade from the Web of Science, PubMed, Embase, Cochrane Library, SinoMed, China National Knowledge Internet, WanFang, and VIP. We performed a meta-analysis of the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels using Review Manager 5.4 software. The trial sequential analysis was conducted to check the results. RESULTS: A total of 45 trials with 5016 patients were included. Meta-analysis results showed that traditional Chinese medicine effectively improved the International Index of Erectile Function 5 questionnaire scores (weighted mean difference = 3.78, 95% confidence interval: 3.12, 4.44; p < 0.001), clinical recovery rates (risk ratio = 1.57, 95% confidence interval: 1.38, 1.79; p < 0.001), testosterone levels (weighted mean difference = 2.42, 95% confidence interval: 1.59, 3.25; p < 0.001) compared with the controls. The single and add-on applications of traditional Chinese medicine could improve the International Index of Erectile Function 5 questionnaire score (p < 0.001). The trial sequential analysis confirmed the robustness of the analysis of the International Index of Erectile Function 5 questionnaire scores. A significant difference in the incidence of adverse effects between the treatment and control groups was not observed (risk ratio = 0.82, 95% confidence interval: 0.65, 1.05; p = 0.12). CONCLUSION: Traditional Chinese medicine can gain better responses in improving the International Index of Erectile Function 5 questionnaire scores, clinical recovery rates, and testosterone levels as an alternative and complementary treatment, with no increase in side effects. However, more standardized, long-term, traditional Chinese medicine and integrative therapy clinical trials are needed to support the clinical application of traditional Chinese medicine.

Efficacy and safety assessment of severe COVID-19 patients with Chinese medicine: A retrospective case series study at early stage of the COVID-19 epidemic in Wuhan, China.

ETHNOPHARMACOLOGICAL RELEVANCE: The coronavirus disease 2019 (COVID-19) has formed a global pandemic since late 2019. Benefitting from the application experience of Chinese Medicine (CM) for influenza and SARS, CM has been used to save patients at the early stage of COVID-19 outbreak in China. AIM OF THE STUDY: In order to evaluate the efficacy and safety of CM, and compare with Western Medicine (WM) for COVID-19, we conducted a retrospective case series study based on the patients in Wuhan Jinyintan Hospital, Wuhan, China. METHODS: The inclusion and exclusion criteria of data extraction were set for this retrospective study. All patients who were admitted by the Wuhan Jinyintan Hospital between January 17th and February 25th 2020 were considered. In addition, patients enrolled met the severe defined by the guidelines released by the National Health Commission of the People's Republic of China. In these cases included in the study, CM or WM treatment was selected according to the wishes of the patients at the beginning of hospitalization. The patients in CM group were treated with Huashi Baidu granule (137 g po, bid) combined with the injections of Xiyanping (100 mg iv, bid), Xuebijing (100 ml iv, bid) and Shenmai (60 ml iv, qd) according to the syndrome of epidemic toxin blocking the lung in the theory of Traditional Chinese Medicine. The WM group received antiviral therapy (including abidor capsule 0.2 g po, tid; Lopinavir-Ritonavir tablets, 500 mg po, bid), antibiotics (such as cefoperazone 2 g iv, bid; moxifloxacin hydrochloride tablets, 0.4 g po, qd) or corticosteroid therapy (such as methylprednisolone succinate sodium 40 mg iv, qd; prednisone, 30 mg po, qd). In addition, patients in both groups received routine supportive treatment, including oxygen inhalation, symptomatic therapy, and/or human intravenous immunoglobulin, and/or serum albumin, and treatment for underlying diseases. The clinical outcomes were evaluated based on changes related with clinical manifestations, computer tomography (CT) scan images, and laboratory examinations before and after the treatment. RESULTS: 55 severe COVID-19 patients, with 23 in CM group and 32 in WM group, were included for analyzed. There was no case of death, being transferred to ICU, or receiving invasive mechanical ventilation in two groups during hospitalization. The median time of SARS-CoV-2 RNA clearance in CM and WM group were 12 days and 15.5 days respectively, the ratio of nucleic acid negative conversion of CM group at different follow-up time points was significantly higher than that of WM group (HR: 2.281, P = 0.018). Further, the chest CT imaging showed more widely lung lesion opacity absorbed in the CM group. The high sensitivity C-reactive protein and serum ferritin decreased significantly in the CM group (P<0.05). There was no significant difference in adverse events in terms of liver function and renal function between the two groups. CONCLUSION: Based on this retrospective analysis from Wuhan Jinyintan Hospital, CM has better effects in SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorbed and reducing inflammation in severe COVID-19 patients, which is effective and safe therapy for treating severe COVID-19 and reducing mortality.

Toxicity and risk assessment of mercury exposures from cinnabar and Baizi Yangxin Pills based on pharmacokinetic and tissue distribution studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Baizi Yangxin Pills (BZYXP), a popular cinnabar (α-HgS) contained Traditional Chinese Medicines (TCMs) is widely used in clinical trials. However, mercury is one of the most toxic elements. The adverse effects of cinnabar-containing TCMs have been occasionally reported in recent years, leading to the growing concerns about their toxicity and safety. AIM OF THE STUDY: The health risks of BZYXP and cinnabar related to the mercury exposures were evaluated through blood pharmacokinetic and tissue distribution studies in rats. MATERIALS AND METHODS: The distribution of absorbed mercury in rats' blood and tissues were measured by the developed cold-vapor atomic fluorescence spectrometric method. And the tissue damages were determined through the histopathological examinations. For single dose study, the low and high oral doses were equivalent to 1 and 10-fold therapeutic dose, respectively. The multiple doses study was conducted at low and high dose levels every 12 h for 30 consecutive days. RESULTS: Significant differences of mercury blood pharmacokinetic and tissue distribution characteristics were observed between the corresponding BZYXP and cinnabar groups. The herbal ingredients in BZYXP promoted the absorption of bio-accessible mercury of cinnabar and prolonged the elimination process, posing potential health risks. Although mercury was found easily accumulated in kidney, liver and brain tissues, kidney and liver didn't show obvious damages even after 30 days consecutive administration of BZYXP or cinnabar at 10-fold clinically equivalent doses. But brain did show some histopathological changes, and autonomic activities of rats decreased, pointing the potential neurotoxicity. CONCLUSIONS: Mercury tend to be accumulated especially when over-dose or prolonged medication with cinnabar-containing TCMs are given. The mercury exposures even at therapeutic doses of BZYXP or cinnabar do pose health risks from the neurotoxicity point of view.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

Efficacy, Safety, and Cost of Therapy of the Traditional Chinese Medicine, Catalpol, in Patients Following Surgical Resection for Locally Advanced Colon Cancer.

BACKGROUND The aim of this study was to evaluate the efficacy, safety, and cost of treatment of the traditional Chinese herbal medicine, catalpol, in patients following surgical resection for locally advanced colon cancer. MATERIAL AND METHODS The 345 patients who had undergone surgical resection for locally advanced colon adenocarcinoma, were divided into three groups: a placebo-treated group (n=115); patients treated with an intraperitoneal injection of 10 mg/kg catalpol twice a day for 12 weeks (treatment group) (n=115); patients treated with 5 mg/kg intravenous bevacizumab twice a week for 12 weeks (control group) (n=115). Serum levels of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) were measured. Patient overall survival (OS), cancer-free survival (CFS), adverse effects, and cost of therapy were evaluated. Statistical analysis included the Wilcoxon rank sum test and Tukey's test for clinicopathological response at 95% confidence interval (CI). RESULTS Patients in the catalpol-treated group had significantly reduced serum levels of CA 19-9 (p=0.0002, q=3.202), CEA (p=0.0002, q=3.007), MMP-2 (p£0.0001, q=6.883), and MMP-9 (p<0.0001, q=3.347). Only non-fatal adverse effects occurred in the catalpol treatment group (p<0.0001, q=5.375). OS and CFS were significantly increased in the catalpol treatment group compared with the placebo group (p<0.0001 q=7.586). The cost of catalpol treatment compared favorably with other treatments (p<0.0001, q=207.17). CONCLUSIONS In this preliminary study, treatment with the Chinese herbal medicine, catalpol, showed benefits in clinical outcome, at low cost, and with no serious complications.

Assessment of in vitro cardiotoxicity of extract fractions and diterpene alkaloids from Aconitum leucostomum Worosch: A short communication.

Aconitum leucostomum Worosch is a traditional Chinese medicine (TCM) and has a broad spectrum of health effects, but with a narrow therapeutic window. It is important to identify both the therapeutic ingredients and the toxic components to better utilize this TCM. The present study investigated the cardiotoxicity of the selected compounds in Aconitum leucostomum Worosch. The effects of extract of A. leucostomum Worosch and the isolated compounds on cardiocardiomyocytes were evaluated in vitro. Five known compounds in this TCM, including three C18-diterpene alkaloids, lappaconitine (2), N-deacetyllappaconitine (3), and ranaconitine (5), and two C19-diterpene alkaloids, delvestidine (1) and anthranoyllycoctonine (4), were isolated from A. leucostomum Worosch. The cardiotoxicity of these components and extract fractions, as measured by lactate dehydrogenase release and apoptosis, was ranked as follows, in descending order: delvestidine>anthranoyllycoctonine>pH 4 fraction>pH 8 fraction>aconitine>N-deacetyllappaconitine>ranaconitine>lappaconitine. The cytotoxicity of these compounds was shown to be dose-dependent, with delvestidine (1) and anthranoyllycoctonine (4) being the two most toxic compounds to cardiomyocytes in our assays. These results provide a basis for future rational use of this TCM, reducing side effects while retaining therapeutic effects.

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. AIM OF THE STUDY: The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. MATERIALS AND METHODS: In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. RESULTS: No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. CONCLUSION: The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic.

[The significance of introducing registry study in the post-marketing safety research for Chinese medicine and pharmacy].

There is a new research model named 'registry study/patient registry' in Western medicine, which could be referred to by Chinese medicine researchers, such as active safety surveillance. This article will introduce registry study from different aspects as the developing history, features, and application in order to inform Chinese medicine researchers of future studies.

[Thinking on risk assessment and risk management of post-marketing Chinese medicine].

Drug risk assessment and management is an important measure for reducing the adverse drug reaction and enhancing medication safety of the patient. Based on the concepts of drug risk assessment and risk management, and domestic and international drug risk management situation, this paper discusses the risk management of post-marketing Chinese medicine.

[Basic requirements on post-marketing clinical re-evaluation of chinese medicine and phase IV clinical trials].

As information on safety and effectiveness is not comprehensive, gained from the researches for listing approval of Chinese medicine, it is very necessary to conduct post-marketing clinical re-evaluation of Chinese medicine. Effectiveness, safety and economic evaluation are three main aspects of post-marketing clinical re-evaluation. In this paper, the difference and relations between the post-marketing clinical re-evaluation and the phase IV clinical trials were discussed, and the basic requests and suggestions were proposed, according to the domestic and foreign relevant regulations and experts' suggestions, and discussed the requirements of the phase IV clinical trials on indications, design methods, inclusion and exclusion criteria, sample size, etc.

[Study on method on post-marketing traditonal Chinese medicine safety assessment].

Traditional Chinese medicine (TCM) safety assessment is an important content of post-marketing Chinese herbal medicine assessment and the primary question. It includes safety monitoring and safety evaluation. China has established the elementary system for the TCM safety monitoring, but did few things on safety evaluation. People have knew that the methods of pharmacoepidemiology have good practicability on drug safety assessment in recent years. This article analyzed three methods of pharmacoepidemiology used in post-marketing Chinese herbal medicine safety assessment. There are three examples that may give some suggestions to fellow doctors working for safety monitoring and evaluation of TCM.

[Evaluation point of rational drug use of traditional Chinese medicine in market].

Minimizing the underlying risk and maximizing the benefits of drag users, by using drags under a safe, efficient and economical principle, is both the requirement and purpose of clinical rational drug use. This paper evaluates the clinical application of traditional Chinese medicine (TCM) in the market based on its characteristics, considering if the drugs are safely applied, if the medicine has an anticipated effect, and if the medicine is properly priced. This paper also brings the idea of establishing an evaluation system integrated with the characteristics of TCM to monitor the clinical application of TCM after going into the market and thus further optimizes the clinical instructions of applying TCM and helps to guide the appropriate usage of TCM.

[Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

Thinking on how to construct the system of Chinese medicine efficacy evaluation for coronary heart disease angina pectoris.

The existing efficacy evaluation for coronary heart disease (CHD) angina pectoris does not demonstrate the characteristics and advantages of Chinese medicine (CM), so a new system of efficacy evaluation which can scientifically and systematically reflect the specific features of CM needs to be urgently set up. Based on wide references of efficacy evaluations of CHD angina pectoris from our country and abroad, and considering the general acceptance by academic circles and demonstration of the characteristics of CM, this paper tries to set up a new index system of efficacy evaluation, combining both disease and syndrome differentiation for CHD angina pectoris. This paper also offers some explorations based on the results of clinical trials. The system is composed of six aspects, including efficacy evaluation of "disease", syndrome factors and main endpoints (the incidence of important clinical events), as well as patient reported outcomes, safety evaluation and medical economics.

Assessment of the safety of Qin Kai Ling injection: a systematic review.

OBJECTIVE: Qin Kai Ling (QKL) injection, which is based upon the traditional Chinese medicine formulation 'An Gong Niu Huang Wan', is widely used in treatment of many diseases. This review aims to assess the safety of QKL. METHODS: We searched Chinese databases CNKI and VIP for articles published between January 1987 and April 2009. RESULTS: A total of 1486 cases were included in this review. We were unable to determine the frequency of ADR/AE induced by QKL due to the lack of complete production and market information. We estimate, based on the limited data, that the risk of ADR/AE from QKL use should be low. We found some ADR/AE may have been induced by incorrect use of QKL, such as use in infants, or use with incompatible drugs, and some places may not suite for use of QKL, for example, four of seven patients died in private clinics or patient's home. We unable to distinguish whether incidents were ADRs or AEs because the poor reports. CONCLUSION: Current evidence, while weak, indicates that QKL carries a low risk of ADR/AE, and some adverse events that do occur may be ascribed to improper use of the drug. Reporting of ADR/AEs needs to be greatly improved, and should follow the 'Recommendations for reporting traditional Chinese medicine adverse drug reaction".

[Advancement of maggot including living body to treat chronic infected wounds].

Human has used maggot to treat diseases for thousands of years. In recent years, with abuse of antibiotic and the rising incidence of antibiotic resistance, maggot therapy, as a surgical alternative, is mainly applied to treat chronic infected wounds on account of its low cost, efficacy and safety. Its mechanisms are disinfection, bio-debridement and enhancement of tissue regeneration. Maggot therapy which serves as a kind of biological therapy is promising. However, living maggot therapy could result in inevitable complications, so that we should apply traditional Chinese medicine theory to investigate and develop new delivery method of maggot. The review summarizes the past and present of maggot therapy.

Traditional Chinese medicine (phytotherapy): Health Technology Assessment report - selected aspects.

OBJECTIVE: A summary of main aspects from a Health Technology Assessment report on Traditional Chinese Medicine (TCM) in Switzerland concerning effectiveness and safety is given. MATERIALS AND METHODS: Literature search was performed through 13 databases, by scanning reference lists of articles and by contacting experts. Assessed were quality of documentation, internal and external validity. RESULTS: Effectiveness: 43 articles concerning 'gastrointestinal tract and liver' were assessed. The studies covering 7,436 patients were undertaken in China (35), Japan (3), USA (2) and Australia (3); 33/43 being controlled studies. 34/40 show significantly better results in the TCM-treated group. A comparison of studies on results of treatment based on a diagnosis according to TCM criteria and studies on results of treatment according to Western diagnosis shows that treatment based on TCM diagnosis improves the result. The comparison of treatment by individual medication and standard medication showed a trend in favor of individual medication. SAFETY: TCM training and practice for physicians in Switzerland are officially regulated. Side effects occur, but no severe effects have been registered up to now in Switzerland. TCM medicinals are imported; admission regulations are being installed. Problems due to production abroad, Internet trade, self-medication or admixtures are possible. CONCLUSION: The evaluation of the literature search provides evidence for a basic clinical effectiveness of TCM therapy. Severe side effects were not observed in Switzerland. Regulations for trading and use of medicinals prevent treatment risks. Further clinical studies in a Western context are required.