Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making.MethodsRandomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results.ResultsA total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively.ConclusionBased on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

Rapid and sensitive liquid chromatography–tandem mass spectrometric method for the quantitative determination of potentially harmful substance 5,5′-oxydimethylenebis (2-furfural) in traditional Chinese medicine injections

With the rapid development and wide application of traditional Chinese medicine injection(TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS)method has been developed and validated for the quantitative determination of potentially harmful substance5,5′-oxydimethylenebis(2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column(150 mm × 2.1 mm, 5 μm) by gradient elution, using methanol–water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 m L/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/m L and linear over the range of 0.3–30 ng/m L(r = 0.9998). Intra-and inter-day precision for analyte was o9.52% RSD withrecoveries in the range 88.0–109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.

Network meta-analysis of 3 kinds of Chinese medicine injection in the treatment of knee osteoarthritis

Objective:To compare the effect of three kinds of traditional Chinese medicine injection(zhengqing fengtongning injection,shenmai injection,cervus and cucumis polypeptide injection)on knee osteoarthritis with the method of Network meta-analysis.Methods:Two researchers independently used computers to search for randomized controlled clinical trials of zhengqing fengtongning injection,shenmai injection,or cervus and cucumis polypeptide injection for the treatment of knee osteoarthritis published in CNKI,VIP,WANFANG DATA,CBM and PubMed databases(since the date of database establishment to February 2020).After the methodological quality of included researches were evaluated,and the valid data were extracted,statistical analysis was performed With RevMan5.3 and R 3.53.Results:There were including 9 RCTs,which involving 720 patients.The results of network Meta-analysis showed that:All three traditional Chinese medicine injections effects are approximately equal.The probability ranking chart shows that Zhengqingfengtongning injection may have the best effect.Conclusions:Three commonly used traditional Chinese medicine injections can effectively treat knee osteoarthritis,of which Zhengqingfengtongning injection is probably the most effective.Due to the small number of literatures included in this study and the single outcome index,we still need to treat the results of this study with caution.It is suggested that more high-quality,long-term follow-up studies should be carried out for this kind of treatment in the future,so as to provide solid evidence support for the popularization of these treatment measures.

Clinical Observation on the Improved Short-Term Effects of Anti-Tumor Purified Chinese Medicine Injection Ai-Jing for 138 Cases with Malignant Tumors

The subjects of this study were to observe the improved short-term effects of anti-tumor purified Chinese medicine injection Ai-Jing for 138 cases with malignant tumors. This was a multi-center clinical study, and a total of 138 patients included 96 males and 42 females, with the age from 60 to 76 years. Ai-Jing has obtained the Chinese invention patent since 2008 (ZL991-03528.3). A novel technique acupoint injection method was adopted. Except for lung cancer, patients with other malignant tumors were injected once every other day, 2 ml each time. A course of treatment needs 6 Ai-Jing injections, lung cancer patients need 10 - 20 Ai-Jing injections. At the same time, patients were treated with traditional medicine decoction. Due to the limited number of cases, cure rate, recovery rate and remission rate were calculated as a whole, respectively 18.12%, 44.20% and 32.15%. All the invalid patients were lung cancer, accounting for 16.67% of the patients treated with lung cancer, and the total treatment inefficiency was 6.52%. Conclusion: Chinese Medicine Injection Ai-Jing extracts the effective components of anti-cancer and tumorigenesis, and has the effects of anti-cancer and tumorigenesis, anti-inflam-matory and analgesic, and repairing body damage, with small toxic and side effects and low cost.

Rapid determination of tannin in Danshen and Guanxinning injections using UV spectrophotometry for quality control

A technique for the determination of tannin content in traditional Chinese medicine injections(TCMI)was developed based on ultraviolet(UV)spectroscopy.Chemometrics were used to construct a mathematical model of absorption spectrum and tannin reference content of Danshen and Guanxinning injections,and the model was veried and applied.The results showed that the established UV-based spectral partial least squares regression(PLS)tannin content model performed well with a correlation coefficient(r)of 0.952,root mean square error of calibration(RMSEC)of 0.476
g/ml,root mean square error of validation(RMSEV)of 1.171
g/ml,and root mean square error of prediction(RMSEP)of 0.465
g/ml.Pattern recognition models using linear discriminant analysis(LDA)and k nearest neighbor(k-NN)classiers based on UV spectrum could successfully classify different types of injections and different manufacturers.The established method to measure tannin content based on UV spectroscopy is simple,rapid and reliable and provides technical support for quality control of tannin in Chinese medicine injections.

TREATMENT OF PRIMARY PALPEBRAL RETRACTION WITH ACUPOINT-INJECTION AND CHINESE MEDICINAL HERBS

In the present paper, the therapeutic effect of combined therapy of acupoint injection and Chinese medicinal herbs was observed in 59 cases of primary palpebral retraction patients. These 59 patients were divided into treatment group (n=38, treated with acupoint injection and Chinese medicinal herbs) and control group (n=21, treated with Chinese medicinal herbs alone). After 3 courses of treatment, of the 38 cases in treatment group, 25 (65.8%) were cured, 8 (21.1%) had marked improvement and 5 (13.2%) had improvement; of the 21 cases in control group, 8 (38.1%) were cured, 9 (42.9%) had marked improvement, 2 (9.5%) had improvement and 2 (9.5%) were ineffective. Statistical analysis showed a significant difference between the two groups in the therapeutic effect. The cure rate of experimental group was apparently higher than that of the control group, i.e. the therapeutic effect of the combined therapy of acupoint injection and Chinese medicinal herbs was superior to that of Chinese medicinal herbs alone.

Application of Traditional Chinese Medicine injection in treatment of primary liver cancer:a review

OBJECTIVE:To investigate the application of Traditional Chinese Medicine Injections(TCMIs) for treatment of primary liver cancer(PLC).METHODS:A literature review was conducted using PubMed/Medline,Cochrane Library Controlled Clinical Trials Database,China National Knowledge Infrastructure(CNKI),China Scientific Journal Database(CSJD) and China Biology Medicine(CBM).Online websites including journal websites and databases of ongoing trials,as well as some Traditional Chinese Medicine journals that are not indexed in the electronic databases were also searched.RESULTS:The literature review showed that TCMIs as adjunctive medication for the treatment of PLC could regulate patient immunity,reduce bone marrow suppression,relieve clinical symptoms,and improve quality of life,as well as control disease progression and prolong survival time.CONCLUSION:Within the limitations of this review,we conclude that application of TCMIs as adjunctive medication may provide benefits for patients with PLC.Further large,high-quality trials are warranted.

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome?A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective To assess the efficacy and safety of Chinese medicine injection(CMI)for treating acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods Randomized controlled trials(RCTs)were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019.The Cochrane Handbook was used to evaluate risk of bias in the included studies.Data analysis was conducted using RevMan 5.3.3 software.Results A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis.The main meta-analysis showed that CMI combined with conventional therapy(CT)was more effective than CT alone in reducing the acute physiology and chronic health evaluation(APACHE)H score[mean difference(MD):−1.74 points,95%confidence interval(CI):−2.77 to−0.71,I^2=0]and increasing the total effective rate[relative risk(RR):1.35,95%CI:1.17 to 1.56,I^2=37%].Compared with CT,CMI combined with CT showed improvements in the arterial partial pressure of oxygen(PaO2,MD:9.25 mm Hg,95%CI:0.87 to 17.63,I^2=98%)and oxygenation index[arterial partial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2),MD:50.75 mm Hg,95%CI:35.18 to 66.31,I^2=94%].CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome(SIRS)score(MD:−0.84 points,95%CI:−1.26 to−0.42,I^2=65%),length of hospital stay(MD:−4.22 days,95%CI:−6.49 to−1.95,I^2=92%),and duration of mechanical ventilation(MD:−2.94 days,95%CI:−4.68 to−1.21,I^2=89%).Only 1 study reported adverse events.Conclusions CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS.However,we could not make a definite conclusion due to low quality of included studies and uncertain security.Future studies should focus on improving research design,especially in blindness and placebo.The reporting of adverse events was also needed.

To Establish A Body of Evidence on Safety for Postmarketing Chinese Medicine：A New Research Paradigm

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in China’s mainland recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for efficacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this field both in China and abroad are urgently needed.

Shuanghuanglian injection downregulates nuclear factor-kappa B expression in mice with viral encephalitis

A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.

Determination of Critical Influencing Factor on pH Stability of Yuxingcao Injection

The change of drug quality of Yuxingcao injection after formulation is considered as one of the causes for adverse reactions. In this study, orthogonal experimental design was used to investigate the influencing factors on the pH stability of Yuxingcao injection. Two methods of accelerated tests were carried out in the experiments. The results showed that using Tween 80 as the solubilizer could significantly decrease the pH value of Yuxingcao injection after accelerated tests. There was no significant difference in the pH value after the accelerated tests when the other 6 factors varied, including the type of liquid processed, the dosage of activated carbon, heating temperature, reagents for pH adjustment, pH value range after adjustment, and sterilization conditions. In order to improve the quality stability of Yuxingcao injection, the quality of Tween 80 should be strictly controlled to minimize the change of pH value of Yuxingcao injection.

Shenfu Injection(参附注射液) Inhibits Inflammation in Patients with Acute Myocardial Infarction Complicated by Cardiac Shock

Objectives： To investigate the effect of Shenfu Injection（参附注射液, SFI） on inflammatory factors in patients with acute myocardial infarction complicated by cardiogenic shock（CS） treated with and intra-aortic balloon pump（IABP）. Methods： This study enrolled 60 patients with ST-segment elevation myocardial infarction（STEMI） complicated by CS. Patients underwent IABP and emergency percutaneous coronary intervention（PCI） were randomly divided into two groups by random number table with 30 cases in each group, one given SFI treatment（100 m L/24 h）, one not. The two groups were then compared in a clinical setting for left ventricular function, biochemical indicators and Inflammatory factors, including C-reactive proteins（CRP）, interleukin-1（IL-1） and tumor necrosis factor alpha（TNF-α）. Major adverse cardiac and cerebrovascular events（MACCE） events were compared between patients of the two groups both in-hospital and in follow-ups. Results： The IABP support treatment times of patients in the IABP＋SFI group were significantly shorter than the IABP group（52.87±28.84 vs. 87.45±87.31, P=0.047）. In the patients of the IABP＋SFI group, the CRP peak appeared in 24 h after PCI operation. The CRP peak in the patients of the IABP＋SFI group was significantly lower than that in the IABP group（31.27±3.93 vs. 34.62±3.47, P=0.001）. The increases in range of TNF-α in the patients of the IABP＋SFI group were significantly lower than those of the IABP group（182.29±22.79 vs. 195.54±12.02, P=0.007）. The increases in range of IL-1 in the patients of the IABP＋SFI group were significantly lower than those of the IABP group（214.98±29.22 vs. 228.60±7.03, P=0.019）. The amplitude elevated TNF-α 72 h after admission was an independent risk factor of in-hospital MACCE events（OR 0.973, 95% CI 0.890–0.987, P=0.014） in patients with STEMI and CS. Conclusion： Patients with STEMI complicated by CS treated by IABP and SFI had a reduced inflammatory reaction, a reduced dependence of CS on IABP and shortened the course of disease.

Sodium Tanshinone Ⅱ A Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials

Objective： To systematically evaluate the effectiveness and safety of Sodium Tanshinone ⅡA Sulfonate Injection（STS） as one adjuvant therapy for treating unstable angina pectoris（UAP）. Methods： Randomized controlled trials（RCTs） of UAP treated by STS were searched in the China National Knowledge Infrastructure Database（CNKI）, VIP Database for Chinese Technical Periodicals（VIP）, Wanfang Database, the Chinese Biomedical Literature Database（CBM）, Web of Science, the Cochrane Library, Embase, and Pub Med, which from inception to January, 2016. The Cochrane Risk Assessment Tool was used to evaluate the methodological quality of the RCTs. The Review Manager 5.3 software was used to conduct the metaanalysis. Results： The results showed that 17 RCTs involving 1,372 patients were included. The meta-analysis indicated that the combined use of STS and Western medicine（WM） in the treatment of UAP can obviously improve the total effective rate [risk ratio（RR）=1.31, 95% confidence interval（CI）（1.24,1.39）, P〈0.0001], and the total effective rate of electrocardiogram [RR=1.43, 95% CI（1.30,1.56）, P〈0.0001], decrease the level of CRP [mean difference（MD）=–3.06, 95%CI（–3.85, –2.27）, P〈0.00001], fibrinogen [MD=–1.03, 95% CI（–1.16, –0.89）, P〈0.00001], and whole blood high shear viscosity [MD=–0.70, 95% CI（–0.92, –0.49）, P〈0.00001]. Additionally, the occurrence of adverse drug reaction of the experimental group was significantly higher than that of the control group [RR=3.57, 95% CI（1.28, 9.94）, P〈0.05]. Conclusions： Compared with WM, the combined use of STS was more effective.