Efficacy and safety of Xiaofeng powder in the treatment of chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria is a group of skin diseases characterized by pruritus and/or vascular oedema and belongs to the category of "addictive rash" in Traditional Chinese Medicine, and its aetiology is closely related to wind evil. Antihistamines are often used in treatment. Although they have certain effects, they also easily cause disease recurrence. Xiaofeng powder treats this disease has a significant effect in improving the disease state and reducing the recurrence rate. However, there is a lack of evidencebased research. This study to systematically evaluate the clinical efficacy of modified Xiaofeng powder in the treatment of chronic urticaria (CU). METHODS: Computer searches of Chinese databases such as China National Knowledge Infrastructure, China Scientific Journal Database, China Biomedical Literature Database, and WanFang Date and foreign databases such as PubMed and the Web of Science were performed. We retrieved published clinical randomized controlled trials of Xiaofeng powder in the treatment of CU from the establishment of the databases to November 2023. The data were extracted from clinical trials that met the inclusion criteria of this study, and the quality was evaluated through the Cochrane Handbook of Systematic Reviews 5.1.0. Finally, a meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: A total of 11 randomized controlled trials involving 1076 patients were included. The cure rate odds ratio (OR) and 95% confidence interval (CI; shown in brackets) were 2.11 [1.45, 3.07]; the total effective rate OR and CI were 2.42 [1.60, 3.68]; the recurrence rate OR and CI were 0.22 [0.15, 0.34]; the adverse reaction rate OR and CI were 0.23 [0.12, 0.45]; and the mean weighted mean difference (MD) and 95% CI (shown in brackets) of itching degree, wind mass size, wind mass number and wind mass duration in symptom and sign integrals were -0.70 [-0.73, 0.67], -0.64 [-0.96, 0.31], , -0.72 [-1.23, 0.22], and -0.68 [-1.13, 0.23], , respectively. CONCLUSION: The clinical efficacy of modified Xiaofeng powder in the treatment of CU is better than that of antihistamine drugs, with lower adverse reaction and recurrence rates and higher safety. However, the quality of clinical research included is relatively low, and findings need to be confirmed by high-quality research.

TIRPnet: Risk prediction of traditional Chinese medicine ingredients based on a deep neural network.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has a history of over 3000 years of medical practice. Due to the complex ingredients and unclear pharmacological mechanism of TCM, it is very difficult to predict its risks. With the increase in the number and severity of spontaneous reports of adverse drug reactions (ADRs) of TCM, its safety has received widespread attention. AIM OF THE STUDY: In this study, we proposed a framework based on deep learning to predict the probability of adverse reactions caused by TCM ingredients and validated the model using real-world data. MATERIALS AND METHODS: The spontaneous reporting data from Jiangsu Province of China was selected as the research data, which included 72,561 ADR reports of TCMs. All the ingredients of these TCMs were collected from the medical website and correlated with the corresponding ADRs. Then, a risk prediction model was constructed based on a deep neural network (DNN), named TIRPnet. Based on one-hot encoded data, our model achieved the optimal performance by fine-tuning some hyperparameters. The ten most commonly used TCM ingredients and their ADRs were collected as the test set to evaluate their performance as objective criteria. RESULTS: TIRPnet was constructed as a 7-layer DNN. The experimental results showed that TIRPnet performs excellently in all indicators, with a sensitivity of 0.950, specificity of 0.995, accuracy of 0.994, precision of 0.708, and F1 of 0.811. CONCLUSIONS: The proposed TIRPnet owns the ability to predict the ADRs of a single TCM ingredient by learning a large number of TCM-related spontaneous reports, which can help doctors design safe prescriptions and provide technical support for the pharmacovigilance of TCM.

Analysis of potential risks of clinical application of Yi Dian Hong and its proprietary Chinese medicines: A review.

Yi Dian Hong, belonging to the Asteraceae family, finds widespread use in traditional Chinese medicine for its effectiveness in clearing heat, detoxifying, promoting blood circulation, reducing swelling, and cooling the blood. Modern medical research has revealed that Yi Dian Hong and its proprietary Chinese medicines possess biological functions such as inhibiting tumor-specific angiogenesis and regulating immune-related molecules. However, studies have identified that the primary component of Yi Dian Hong contains pyrrolizidine alkaloids (PAs), a toxic substance with potential risks to the liver, lungs, genes, and a propensity for carcinogenicity. Many countries impose strict controls on the content of PAs in herbal medicines and products. Unfortunately, China currently lacks relevant content standards, thereby introducing greater clinical application risks. To ensure the safety of clinical use of Yi Dian Hong, this review will analyze the risk associated with Yi Dian Hong and its proprietary Chinese medicines in clinical applications based on the PAs content in these medicines and provide recommendations.

Efficacy and safety of traditional Chinese medicine in the treatment of menopause-like syndrome for breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: In recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated. METHODS: A comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence. RESULTS: This review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = - 1.84, 95% confidence interval, CI [- 2.21--1.46], Z = 9.63, P < 0.00001). Regarding the main symptoms of MLS, the TCM groups could significantly decrease the scores of hot flashes and night sweats (SMD = - 0.68, 95% CI [- 1.1--0.27], Z = 3.24, P = 0.001), paraesthesia (SMD = - 0.48, 95% CI [- 0.74--0.21], Z = 3.53, P = 0.0004), osteoarthralgia (SMD = - 0.41, 95% CI [- 0.6-0.21], Z = 4.09, P < 0.0001), anxiety (MD = - 0.85, 95% CI [- 1.13, - 0.58], Z = 6.08, P < 0.00001) and insomnia (MD = - 0.61, 95% CI [- 0.8, - 0.43], Z = 6.51, P < 0.00001). TCM can effectively improve the symptoms of MLS in patients with BC. Moreover, TCM could improve the objective response rate (ORR) by 50% (RR = 1.5, 95% CI [1.37-1.64], Z = 9.01, P < 0.00001). Follicle-stimulating hormone (FSH) and oestradiol (E2) had no significant difference compared with the control group (p = 0.81 and p = 0.87), and luteinizing hormone (LH) in the TCM group decreased significantly (MD = - 0.99, 95% CI [- 1.38, - 0.5], Z = 5.01, P < 0.00001). This means that the use of TCM does not negatively affect endocrine therapy and may even have a synergistic effect. The incidence of adverse events (AEs) was lower in the TCM groups than in the control groups. CONCLUSIONS: The meta-analysis stated that TCM could better improve the MLS of patients, alleviate related symptoms, and did not increase adverse drug reactions in BC survivors. This review brings more attention to MLS, and the present findings shed light on the potential applications of TCM in the treatment of MLS in BC survivors.

Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure.

Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T-QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T-QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N-QY305, a subunit nanostructure contained in T-QY305, and confirm its role as potentially being the biomaterial conferring to T-QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T-QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T-QY305, lead to further process to the isolation of N-QY305 from T-QY305, in order to demonstrate that the potency of T-QY305 originates from the nanostructure N-QY305. Compared to T-QY305, N-QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the "King" of Chinese medicine formula as the pharmacodynamic basis.

Mechanisms of multi-omics and network pharmacology to explain traditional chinese medicine for vascular cognitive impairment: A narrative review.

BACKGROUND: The term "vascular cognitive impairment" (VCI) describes various cognitive conditions that include vascular elements. It increases the risk of morbidity and mortality in the elderly population and is the most common cognitive impairment associated with cerebrovascular disease. Understanding the etiology of VCI may aid in identifying approaches to target its possible therapy for the condition. Treatment of VCI has focused on vascular risk factors. There are no authorized conventional therapies available right now. The medications used to treat VCI are solely approved for symptomatic relief and are not intended to prevent or slow the development of VCI. PURPOSE: The function of Chinese medicine in treating VCI has not yet been thoroughly examined. This review evaluates the preclinical and limited clinical evidence to comprehend the "multi-component, multi-target, multi-pathway" mechanism of Traditional Chinese medicine (TCM). It investigates the various multi-omics approaches in the search for the pathological mechanisms of VCI, as well as the new research strategies, in the hopes of supplying supportive evidence for the clinical treatment of VCI. METHODS: This review used the Preferred Reporting Items for Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. Using integrated bioinformatics and network pharmacology approaches, a thorough evaluation and analysis of 25 preclinical studies published up to July 1, 2023, were conducted to shed light on the mechanisms of TCM for vascular cognitive impairment. The studies for the systematic review were located using the following databases: PubMed, Web of Science, Scopus, Cochrane, and ScienceDirect. RESULTS: We discovered that the multi-omics analysis approach would hasten the discovery of the role of TCM in the treatment of VCI. It will explore components, compounds, targets, and pathways, slowing the progression of VCI from the perspective of inhibiting oxidative stress, stifling neuroinflammation, increasing cerebral blood flow, and inhibiting iron deposition by a variety of molecular mechanisms, which have significant implications for the treatment of VCI. CONCLUSION: TCM is a valuable tool for developing dementia therapies, and further research is needed to determine how TCM components may affect the operation of the neurovascular unit. There are still some limitations, although several research have offered invaluable resources for searching for possible anti-dementia medicines and treatments. To gain new insights into the molecular mechanisms that precisely modulate the key molecules at different levels during pharmacological interventions-a prerequisite for comprehending the mechanism of action and determining the potential therapeutic value of the drugs-further research should employ more standardized experimental methods as well as more sophisticated science and technology. Given the results of this review, we advocate integrating chemical and biological component analysis approaches in future research on VCI to provide a more full and objective assessment of the standard of TCM. With the help of bioinformatics, a multi-omics analysis approach will hasten the discovery of the role of TCM in the treatment of VCI, which has significant implications for the treatment of VCI.

Clinical efficacy and molecular mechanism of Chinese medicine in the treatment of autoimmune thyroiditis.

ETHNOPHARMACOLOGICAL RELEVANCE: Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. AIM OF THE STUDY: The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. MATERIALS AND METHODS: The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. RESULTS: An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. CONCLUSIONS: The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways.

[hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine].

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.

Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine.

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading cause of malignancy-related death. Ulcerative coloproctitis (UC) is a precancerous lesion, and UC-associated CRC (UC-CRC) is the most common subtype of CRC. Therefore, a reasonable UC-CRC model is the cornerstone and guarantee of new drug development. Traditional Chinese medicine (TCM) has been widely used in the treatment of UC-CRC due to its good efficacy. As a classic tonic prescription of TCM, Liujunzi decoction (LJZD) has been widely used in the treatment of UC-CRC. In this study, a UC-CRC model was established by combining azomethane and dextran sulfate sodium, and the LJZD was administered. The data confirmed that LJZD can effectively inhibit cancer transition in UC-CRC by using mouse body weight, colorectal length, pathological and inflammatory factors, colorectal barrier function, and cancer markers. This protocol provides a system for evaluating the efficacy of TCM in the prevention and treatment of UC-CRC.

[Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules].

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.

[New outlook on safety of traditional Chinese medicine: concept and practice].

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.

Pinellia ternata-containing traditional Chinese medicine combined with 5-HT3RAs for chemotherapy-induced nausea and vomiting: A PRISMA-compliant systematic review and meta-analysis of 22 RCTs.

BACKGROUND: Pinellia ternata (P. ternata, Banxia)-containing traditional Chinese medicine (TCM) is widely used in China as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV). However, evidence of its efficacy and safety remains limited. PURPOSE: To investigate the efficacy and safety of P. ternata-containing TCM combined with 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) in the treatment of CINV. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant RCTs were systematically retrieved from seven internet databases (up to February 10, 2023). P. ternata-containing TCM combined with 5-HT3RAs to treat CINV was included in all RCTs. The clinical effective rate (CER) was defined as the primary outcome, while appetite, quality of life (QOL), and side effects were secondary outcomes. RESULTS: The meta-analysis included 22 RCTs with 1,787 patients. Our results indicated that P. ternata-containing TCM combined with 5-HT3RAs significantly improved the CER of CINV (RR = 1.46, 95% CI = 1.37-1.57, p < 0.00001), appetite (RR = 1.77, 95% CI = 1.42-2.20, p < 0.00001), QOL (RR = 7.67, 95% CI = 1.56-13.78, p = 0.01), the CER of several 5-HT3RA medications (RR = 1.47, 95% CI = 1.37-1.57, p < 0.00001), and acute and delayed vomiting (RR = 1.23, 95% CI = 1.12-1.36, p < 0.0001) compared with the 5-HT3RAs alone, while the combination therapy decreased the incidence of side effects induced by 5-HT3RAs for CINV (RR = 0.50, 95% CI = 0.42-0.59, p < 0.00001). CONCLUSION: According to the findings of this systematic review and meta-analysis, P. ternata-containing TCM combined with 5-HT3RAs was safer and more effective than 5-HT3RAs alone for CINV patients. However, due to the limitations of the included studies, more high-quality clinical trials are required to further validate our findings.

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

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 of Chinese herbal medicine children's Zibei Xuanfei syrup in treating acute trachea-bronchitis with wind-heat invading lung syndrome: A randomized, double-blind, multicentre, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx. AIM OF THE STUDY: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome. MATERIALS AND METHODS: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit. RESULTS: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug. CONCLUSION: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children.

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.

Safety evaluations of the processed lateral root of Aconitum carmichaelii Debx. And its hepatotoxicity mechanisms in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The processed lateral root of Aconitum carmichaelii Debx. is known as Fuzi, an extensively used Traditional Chinese Medicine to treat cardiovascular diseases, rheumatism arthritis, bronchitis, pains, and hypothyroidism, etc. Although Chinese Pharmacopeia regulates the safe clinical dosage of Fuzi at 3-15 g/person/day, such recommendation not only lacks bench evidence but also does not differentiate Fuzi with different processing types, such as Heishunpian and Paofupian. AIM OF THE STUDY: The current study aimed to 1) determine No-Observed-Adverse-Effect-Levels of Heishunpian and Paofupian in rats and 2) investigate the related toxicity mechanisms for their safe clinical use. MATERIALS AND METHODS: After giving clinically relevant dosing regimen of Heishunpian/Paofupian to rats, we conducted toxicity assessments including ECG monitoring, histopathological changes and serum biomarkers to detect organ injury. Metabolomic study in the liver revealed changes in endogenous metabolite levels after two-week treatment of Fuzi preparations or its corresponding six toxic alkaloids mixtures. RESULTS: The NOAEL for both bolus and two-week treatments of Heishunpian and Paofupian in rats was designated to be 7.5 g/kg and 15 g/kg, respectively. Corresponding recommended doses in humans were 7.5-25 g/person/day for Heishunpian and 15-50 g/person/day for Paofupian. Metabolic profiles revealed more significant alterations in endogenous substances from rats receiving the two Fuzi preparations than their corresponding toxic alkaloids mixtures. Upregulation of bile acid pathway could be responsible for Fuzi induced liver injury. CONCLUSIONS: Compared to the current maximum recommended dose, our suggested upper limit of guided dose for Heishunpian was comparable, whereas that for Paofupian could be further elevated. Both C19-diterpenoid alkaloids and co-occurring components in Fuzi preparations contributed to their hepatotoxicity via upregulation of bile acid pathway.

The safety of Chinese medicine: A systematic review of endogenous substances and exogenous residues.

BACKGROUND: Safety and toxicity have become major challenges in the internationalization of Chinese medicine. Inspite of its wide application, security problems of Chinese medicine still occur from time to time, raising widespread concerns about its safety. Most of the studies either only partially discussed the intrinsic toxicities or extrinsic harmful residues in Chinese medicine, or briefly described detoxification and attenuation methods. It is necessary to systematically discuss Chinese medicine's extrinsic and intrinsic toxic components and corresponding toxicity detoxification or detection methods as a whole. PURPOSE: This review comprehensively summarizes various toxic components in Chinese medicine from intrinsic and extrinsic. Then the corresponding methods for detoxification or detection of toxicity are highlighted. It is expected to provide a reference for safeguards for developing and using Chinese medicine. METHODS: A literature search was conducted in the databases, including PubMed, Web of Science,Wan-fang database, and the China National Knowledge Infrastructure (CNKI). Keywords used were safety, toxicity, intrinsic toxicities, extrinsic harmful residues, alkaloids, terpene and macrolides, saponins, toxic proteins, toxic crystals, minerals, heavy metals, pesticides, mycotoxins, sulfur dioxide, detoxification, detection, processing (Paozhi), compatibility (Peiwu), Chinese medicine, etc., and combinations of these keywords. All selected articles were from 2006 to 2022, and each was assessed critically for our exclusion criteria. Studies describe the classification of toxic components of Chinese medicine, the toxic effects and mechanisms of Chinese medicine, and the corresponding methods for detoxification or detection of toxicity. RESULTS: The toxic components of Chinese medicines can be classified as intrinsic toxicities and extrinsic harmful residues. Firstly, we summarized the intrinsic toxicities of Chinese medicine, the adverse effects and toxicity mechanisms caused by these components. Next, we focused on the detoxification or attenuation methods for intrinsic toxicities of Chinese medicine. The other main part discussed the latest progress in analytical strategies for exogenous hazardous substances, including heavy metals, pesticides, and mycotoxins. Beyond reviewing mainstream instrumental methods, we also introduced the emerging biochip, biosensor and immuno-based techniques. CONCLUSION: In this review, we provide an overall assessment of the recent progress in endogenous toxins and exogenous hazardous substances concerning Chinese medicine, which is expected to render deeper insights into the safety of Chinese medicine.

Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

New outlook on safety of traditional Chinese medicine: concept and practice / 中国中药杂志

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.