Bing Zhang

Objective: The study aimed to establish a benefit-risk assessment (BRA) model utilizing multi-criteria decision analysis (MCDA), in order to evaluate the benefit-risk relationship of decoctions containing Aconitum carmichaeli Debx. (Fuzi) in the treatment of rheumatoid arthritis (RA), laying the foundation for the decision-making on the use of clinical toxic botanical drugs and facilitating their rational application. Methods: The BRA framework of Fuzi in the treatment of RA was evaluated through an intergrated approach combining Delphi survey, meta-analysis, MCDA modeling, and Bayesian Monte Carlo simulations. And also, the variations in benefits and risks when using Fuzi under different conditions were simulated. The modeling of MCDA-BRA was employed various software tools, including Microsoft Office Excel 2016, Matlab R2014b, RevMan 5.4, Hiview 3, and Crystal Ball 11.1.2.4. Results: Based on the Delphi survey results involving 22 experts, a MCDA model for the BRA assessment of Fuzi in RA treatment was constructed. The benefit criteria wighted at 49%, and encompassed secondary criteria such as the number of joints with pressure pain, the number of swollen joints, the duration of morning stiffness, and laboratory test markers. While risk criteria constituted 51% and included factors such as the incidence rate of adverse drug reactions/events (ADRs/ADEs) and damage to various bodily systems. After including 40 random clinical trials (RCTs) that used Fuzi as a primary therapeutic agent in traditional Chinese medicines (TCM) decoction for RA, a meta-analysis was conducted. Combination of the meta-analysis results and BRA model, the BRA value of Fuzi in the treatment of RA was ranging from 5 to 54, which means the benefit is superior to the risk of using Fuzi for RA. RA patients with the pattern of cold and heat complex, 3–15 g dosage, lasting 2–3 months treatment course, and using decoction only, the risks borne by the patients were lower. Sensitivity analysis indicated stability of the evaluation outcomes. Conclusion: The study, utilizing Fuzi in the treatment of RA as an example, effectively explored the methodology of BRA for toxic botanical drugs. It simulated medication regimens that were more favorable to patients and established a solid foundation for risk management and the rational use of toxic TCM in clinical practice. However, interpretation of the findings should account for limitations in the underlying data.

As a miraculous Xinjiang Uyghur customary traditional Chinese medicine (TCM), Chicory (Cichorium glandulosum Boiss.et Huet and Cichorium intybus L.) has been found to have therapeutic potential for metabolic diseases in recent years. Although it is widely used as an ethnic medicine, there is still a lack of targeted quality control indicators in quality standards. Hence, this study was conducted to further develop a strategy to reveal bioactive-chemical quality markers based on the existing foundation. First, through the comparative screening of fingerprint profiles of a large amount of Cichorium glandulosum Boiss.et Huet and Cichorium intybus L., superiority components were found to be potential indicators of chemical quantitative properties for the roots and above-ground parts. The results of content determination showed that their contents differed among different species and parts. Second, the potential dominant components were further confirmed using network pharmacology and molecular docking techniques. Again, the results of RAW264.7 cells and L02 cells experiments showed that chicory acid and lactucin were the main components that could reflect the anti-inflammatory and uric acid-lowering potential of chicory. Finally, under this strategy, this study reveals that cichoric acid and lactucin have the properties of quality markers and quality control of chicory. In a word, this work contributes to the quality control, standard improvement, and rational clinical use of chicory.

Arsenic in environmental health has caused public concerns all over the world. However, high levels of arsenic residues in medicinal animals have not received enough attention. Medicinal earthworms are consumed widely in China, but its arsenic potential health risks to humans are unknown. This work investigated the total concentration, bioaccessibility, and speciation of arsenic in earthworms by ICP-MS and HPLC-ICP-MS to evaluate its potential health risks to humans. Arsenic was found in all earthworms at concentrations ranging from 0.4 to 53.6 mg kg⁻¹. The bioaccessibility of arsenic (bAs) varied significantly and ranged from 12.1 to 69.1%, with inorganic arsenic (iAs, including As(III) and As(V)) as the predominant species. Furthermore, a small amount of arsenobetaine (AB) was found. The estimated daily intake dose (EDI), hazard quotient (HQ), and carcinogenic risk (CR) of arsenic in most of the samples exceeded the safe threshold level. Results from this study indicated that the potential health risks by the consumption of earthworms may not be negligible. Herein, recommendations for the use of earthworms and regulatory recommendations for arsenic limit standards were proposed. This study reminds us that more control and monitoring of arsenic in medicinal animals should be carried out.

Background: Esophageal cancer is one of the most common human cancers, and its incidence is significantly endemic in China. The combination of Chinese herbal injections (CHIs) with radiotherapy should be informed by the best available evidence. To update and expand the previous work to compare and rank CHIs combined with radiotherapy against esophageal cancer. Methods: We searched several electronic databases to identify randomized controlled trials (RCTs) regarding CHIs against esophageal cancer from their inception to Mar 15, 2017. In network meta-analysis (NMA), and the bias of included trails was assessed in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. Outcomes such as the clinical effectiveness rate, performance status, adverse reactions (ADRs) and survival rate were evaluated. We performed a random-effects NMA to obtain estimates for efficacy and safety outcomes and presented these estimates as odds ratios (ORs) and corresponding 95% confidence intervals (CIs) via Stata 13.1 and WinBUGS 1.4 software. Furthermore, the surface under cumulative ranking curve (SUCRA) was performed to rank efficacy and safety of different CHIs for outcomes. Results: We identified 685 citations and of these included 55 eligible trials comprising 12 CHIs and 4114 participants. The results of cluster analysis indicated that the therapy of Compound kushen injection might be the optimal treatment for patients with esophageal cancer in improving clinical effectiveness rate and performance status than other CHIs. Besides, Huachansu and Kangai injection exhibited the superior response for improving 1-year and 2-year survival rate. Moreover, Lentinan injection may be considered as a favorable choice for reliving ADRs, and Compound kushen injection could provide treatment benefits for reducing both gastrointestinal reaction and radiation esophagitis. Conclusions: The current clinical evidence indicated that Compound kushen injection combined with radiotherapy had the potential to be the most preferable and beneficial option for patients with esophageal cancer on balance of efficacy and safety. However, the results for our study should be interpreted with caution that limited by the sample size and methodological quality of included trails.

Chinese herbal injections (CHIs) are prepared by extracting and purifying effective substances from herbs (or decoction pieces) using modern scientific techniques and methods. CHIs combined with aspirin + anticoagulants + dehydrant + neuroprotectant (AADN) are believed to be effective for the treatment of acute cerebral infarction (ACI). However, no randomized controlled trial (RCT) has been performed to directly compare the efficacies of different regimens of CHIs. Therefore, we performed a systematic review and network meta-analysis (NMA) to compare the efficacies of different regimens of CHIs for ACI. We conducted an overall and systematic retrieval from literature databases of RCTs focused on the use of CHIs to treat ACI up to June 2016. We used the Cochrane Handbook version 5.1.0 and CONSORT statement to assess the risk of bias. The data were analyzed using STATA 13.0 and WinBUGS 1.4.3 software. Overall, 64 studies with 6225 participants involving 15 CHIs were included in the NMA. In terms of the markedly effective rate, Danhong (DH) + AADN had the highest likelihood of being the best treatment. In terms of the improvement of neurological impairment, Shuxuening (SXN) + AADN had the highest likelihood of being the best treatment. Considering two outcomes, injections of SXN, Yinxingdamo (YXDM), DH, Shuxuetong (SXT), HongHuaHuangSeSu (HHHSS), DengZhanXiXin (DZXX) and Shenxiong glucose (SX) plus AADN were the optimum treatment regimens for ACI, especially SXN + AADN and YXDM + AADN. Based on the NMA, SXN, YXDM, DH, SXT, HHHSS, DZXX and SX plus AADN showed the highest probability of being the best treatment regimens. Due to the limitations of the present study, our findings should be verified by well-designed RCTs.

To systematically evaluate the clinical effectiveness and safety of Danshen Injection (丹参注射液, DS) as one adjuvant treatment for conventional therapy with Western medicine (WM) for unstable angina pectoris (UAP). Using literature databases, a thorough and systematic retrieval of randomized controlled trials (RCTs) comparing DS plus WM with WM was conducted from inception to April 2015. The extracted data from included studies was analyzed by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg's and Egger's tests conducted by Stata 12.0 were used to evaluate the potential presence of publication bias. A total of 17 RCTs, which involving 1,433 participants, were identified and reviewed. The meta-analysis indicated that the combined use of DS and WM was significantly superior to WM alone for UAP in terms of the total effectiveness rate of angina pectoris [risk ratio (RR) =1.23, 95% confidence interval (CI): 1.17, 1.29, P P=0.001]. Additionally, DS could also further reduce the content of fibrinogen, adjust blood lipid level, correct T wave inversion, and so on. Fifteen adverse drug reactions were reported in two studies, Four of which appeared in the experimental group. Based on the systematic review, the combined use of DS and WM was more effective than WM alone, it can be further widely used in clinic, however, there was no exact conclusion for its safety.

To systematically evaluate the clinical efficacy and safety of Salvianolate injection in the treatment of unstable angina pectoris (UAP). Using literature databases, we conducted a thorough and systematic retrieval of randomized controlled trials (RCTs) that using Salvianolate injection for treating UAP. The Cochrane Risk of Bias Assessment Tool was used to evaluate the methodological quality of the RCTs, and then the data were extracted and meta-analyzed by RevMan5.2 software. A total of 22 RCTs with 2050 participants were included. The meta-analysis indicated that the combined use of Salvianolate injection and western medicine (WM) in the treatment of UAP can achieve a superior effect in angina pectoris total effective rate (risk ratio [RR] = 1.22, 95% confidence interval [CI] (1.17, 1.27), Z = 10.15, P < 0.00001], and the total effectiveness rate of electrocardiogram [RR = 1.26, 95% CI (1.19,1.34), Z = 7.77, P < 0.00001]. In addition, Salvianolate injection can improve the nitroglycerin withdrawal rate and the serum level of NO, decrease high-sensitivity C-reactive protein. Adverse drug reactions (ADRs) or adverse drug events (ADEs) were reported in 6 RCTs involving 15 cases; however, there were no serious ADRs/ADEs. Based on the systematic review, the combined use of Salvianolate injection and WM in the treatment of UAP can achieve a better effect; however, there was no definitive conclusion about its safety. More the large-sample and multicenter RCTs are needed to support its clinical usage.