Reduning Injection Research Articles

Efficacy of five different traditional Chinese medicine injections in acute upper respiratory tract infection in children: a network meta-analysis and systematic review.

Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional Chinese medicine (TCM) injections are widely used for treating AURI in clinical practice, but their efficacy is unclear because of the lack of clear evidence. In this study, a network meta-analysis (NMA) was used to evaluate the efficacy and safety of TCM injections in the treatment of AURI and to provide a reference for clinical treatment. Eight databases were searched, namely, PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), the Wanfang database, and the Chinese Scientific Journal database (VIP). The search time period was from 1 January 2013 to 1 November 2023. Randomized controlled trials of herbal injections for treating AURI were searched. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of these studies. Review Manager 5.4 and Stata 15.0 were used for the NMA. A total of 81 papers involving 11,736 patients were included. These involved five different TCM injections, namely, Xiyanping injection (XYPI), Qingkailing injection (QKLI), Reduning injection (RDNI), Yanhuning injection (YHNI), and Tanreqing injection (TRQI). QKLI was most effective in alleviating symptoms of fever and improving overall clinical effectiveness. TRQI was most effective in relieving cough symptoms. YHNI was most effective in alleviating sore throat, runny nose, and nasal congestion. The overall incidence of adverse effects of these herbal injections in the treatment of AURI was lower, and their safety profiles were better. The herbal injections combined with ribavirin improved clinical outcomes, and were superior to ribavirin injection alone in alleviating clinical symptoms such as fever, cough, sore throat, runny nose, and nasal congestion, and have favorable safety profiles. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023484099, CRD42023484099.

Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

Antipyretic and Anti-Inflammatory Effects of Rectal Administration of Reduning Injection in Feverish Rats Induced by Lipopolysaccharide.

This study aimed to explore the antipyretic and anti-inflammatory effects of rectal administration of Reduning injection in feverish rats induced by lipopolysaccharide (LPS), and observe the temperature changes and inflammatory indexes. The selected rats were randomly divided into 6 groups, with 10 rats in each group, named as normal empty group, model group, intravenous group (2 mL/kg), low-dose enema group (1 mL/kg), middle-dose enema group (2 mL/kg), and high-dose enema group (4 mL/kg). The hourly temperature variations in rats injected with LPS in the abdomen were recorded. Five hours later, blood samples from the abdominal aorta were collected to monitor immunoglobulin M (IgM), immunoglobulin A (IgA), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. At 5 hours, the fever peak induced by LPS appeared, and obvious antipyretic effects were observed; the effect was optimal in the medium dose enema group at 4 hours (p < 0.05); the IgM value in the enema groups, the intravenous group, and normal empty group was significantly lower than that in the model group; the IgA value in each group was higher than that in the model group, but there was no statistical significance (p > 0.05); values of IL-6 and TNF-α in each group were lower than those in the model group, and the difference was statistically significant except for the high-dose enema group (p > 0.05). Low-dose and medium-dose rectal administration of Reduning injection have inhibitory effects on IL-6, TNF-α, and IgM in feverish rats induced by LPS, but there is no obvious difference compared to intravenous administration and it could achieve an anti-inflammatory effect. There is a possibility of enhancing IgA immunity with rectal administration, but there is no obvious difference compared to intravenous administration, and rectal administration has no significant effect on mucosal immunity.

Guideline on treating community-acquired pneumonia with Chinese patent medicines

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

RDN for the treatment of influenza in children: a randomized, double-blinded, parallel-controlled clinical trial

BackgroundThe morbidity of influenza in children increased rapidly in decade. Reduning injection (RDN), a small but fine Chinese herbal formula, has antipyretic, antiviral, anti-inflammatory effects. We intend to evaluate the efficacy and safety of RDN for the influenza in children versus Oseltamivir, explore the possible antiviral mechanism of RDN and provide evidence-based medical evidence for rational clinical drug usage.MethodWe design a randomized, double-blind, double-dummy, parallel control of positive drug, multi-centre clinical study. According to the formula of mean superiority test, a total of 240 patients with influenza in children will be randomized 1:1 into the experimental group and control group. The experimental group will take RDN and Oseltamivir phosphate granule simulants and the control group will take Oseltamivir phosphate granule and RDN simulants. Each group will be treated for 5 days. The primary outcome measure is temperature recovery time, and the secondary outcome measures include time when the fever begins to subside, time and degree of disease to alleviate, disappearance rate of individual symptoms and so on. We will measure before enrollment and each 24 h after treatment for comparison.DiscussionThe study is launched to evaluate the efficacy and safety of RDN for the treatment of influenza in children and to provide an alternative option for influenza in children.Trial registrationThis study is registered in ClinicalTrials.gov as NCT04183725, registered on 3 December, 2019.

Pathway network-based quantitative modeling of the time-dependent and dose-response anti-inflammatory effect of Reduning Injection.

Traditional Chinese medicine (TCM) has extensive healing effects on inflammatory diseases with few side effects. Reduning injection (RDNI), a TCM prescription composed of Lonicera japonica Thunb., Gardenia jasminoides Ellis. and Artemisia annua L., is wildly used for treating inflammatory diseases. However, the mechanism of action of RDNI, like most TCM prescriptions, is unclear due to the complexity of relationships between components and their curative effects. To develop a universal systems pharmacology protocol for mechanism modeling of TCM and apply it to reveal the real-time anti-inflammatory effect of Reduning Injection. Combined with database mining and references, a regulatory mechanism network of inflammation was constructed. A quantitative model was established afterwards by integrating pharmacokinetic data and two network parameters, namely Network Efficiency and Network Flux. The time-dependent and dose-response relationship of RDNI on the regulation of inflammation was then quantitatively evaluated. ELISA tests were performed to verify the reliability of the model. Three cytokines, namely IL-1β, IL-6 and TNF-α were screened out to be markers for evaluation of the anti-inflammatory effect of RDNI. An HPLC method for the simultaneous determination of 10 RDNI compounds in SD rat plasma was established and then applied to pharmacokinetic studies. Based on compound activity and pharmacokinetic data, the time-dependent effect of RDNI were quantitatively predicted by the pathway network-based modeling procedure. The quantitative model established in this work was successfully applied to predict a TCM prescription's real-time dynamic healing effect after administration. It is qualified to provide novel insights into the time-dependent and dose-effect relationship of drugs in an intricate biological system and new strategies for investigating the detailed molecular mechanisms of TCM.

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis

ObjectiveTo elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. MethodsRat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. ResultsA total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE2) and pharmacodynamic indicators (IL-6, IL-1β, PGE2 and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance. ConclusionRDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.

Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1β, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 μg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P&lt;0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P&lt;0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P&lt;0.05), and the proportion of T cells was recovered dramatically(P&lt;0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 μg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1β, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Pharmacokinetic Study of Coadministration with Cefuroxime Sodium for Injection Influencing ReDuNing Injection-Derived Seven Phytochemicals and Nine Metabolites in Rats.

According to the sixth edition of China's “New Coronavirus Diagnosis and Treatment Plan (NCDTP),” ReDuNing injection (RDN) was firstly introduced to treat severe and critical COVID-19, whereas its combination with broad-spectrum antibiotics was suggested to take with extreme caution and full reasons. Therefore, we aim to describe the pharmacokinetics of seven active phytochemicals and semiquantification of nine relevant metabolites in ReDuNing injection (RDN) after combining with cefuroxime sodium (CNa) for injection in rat plasma. Male Sprague–Dawley rats were randomly assigned to six groups, and they were intravenously administered, respectively, with different prescriptions of RDN (2 mL/kg) and CNa (225 mg/kg). At different time points (0.03, 0.08, 0.17, 0.24, 0.33, 0.50, 0.67, 1, and 6 h) after administration, the drug concentrations of iridoids glycosides, organic acids, and metabolites in rat plasma were determined using ultrahigh-pressure liquid chromatography coupled with linear ion rap-orbitrap tandem mass spectrometry (UHPLC–LTQ–Orbitrap–MS), and main pharmacokinetic parameters were estimated by noncompartment model. The results showed that there were differences in pharmacokinetic parameters, AUC(0-t), T1/2, Cmax, CL of iridoids glycosides, and organic acids, after the intravenous administration of the different combinations of RDN and CNa. Moreover, different combinations of the injections also resulted in different curves of relative changes of each metabolite. The obtained results suggested that RDN and CNa existed pharmacokinetic drug–herb interactions in rats. The findings not only lay the foundation for evaluating the safety of RDN injection combined with CNa but also make contributions to clinically applying RDN injection combined with CNa, which works potentially against severe forms of COVID-19.

Clinical Observation of Reduning Combined with Recombinant Human Interferon α-2b in the Treatment of Children with Viral Pneumonia.

Purpose To observe the clinical efficacy of Reduning injection combined with recombinant human interferon α-2b spray in the treatment of children with viral pneumonia. Methods A total of 200 children with viral pneumonia over 2 years old who were admitted to the Pediatrics Department of the Cangzhou Central Hospital from September 2018 to November 2020 were recruited and randomized into the control group and observation group at a ratio of 1 : 1, with 100 cases in each group. The children in the control group were given recombinant human interferon α-2b spray, and the children in the observation group were given Reduning injection on the basis of the control group. The clinical symptoms and signs, clinical efficacy, levels of inflammatory mediators, and drug safety were compared between the two groups. Results The t-test results showed that the disappearance time of body temperature, respiratory rate, pulmonary rales, and cough in the observation group was significantly shorter than that in the control group. The chi-square revealed a significantly higher total effective rate in the observation group vs. the control group. After treatment, the levels of IL-1, IL-6, TNF-α, and CRP in the two groups were lower than the corresponding values before treatment, and greater reduction was observed in the observation group in relative to the control group (both p < 0.05). The two groups have a similar safety profile. Conclusion Reduning combined with recombinant human interferon α-2b produces a remarkable effect in the treatment of children with viral pneumonia, and it ameliorates clinical symptoms and reduces inflammatory response with a good safety profile.

Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition.

BackgroundRadiation-induced lung injury (RILI) is a common side effect in chest radiotherapy patients, and there is no good medicine to treat it. Re-Du-Ning (RDN) injection is a traditional Chinese medicine that is clinically used to treat upper respiratory tract infections and acute bronchitis. RDN has the advantage of high safety and mild side effects. The mechanism of most traditional Chinese medicine preparations is unknown. PurposeTo illustrate the mechanisms of RDN for the treatment of RILI. MethodsFemale C57BL/6 mice were used to establish a RILI model via irradiation, and RDN injection was intraperitoneally administered at doses of 5, 10, and 20 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to Absent in melanoma 2 (AIM2) inflammasome were analyzed via ELISA and a network pharmacological approach. In addition, the data related to epithelial-mesenchymal transition (EMT) were analyzed via immunofluorescence, Western blotting, and a network pharmacological approach. ResultsRDN robustly alleviated RILI. Meanwhile, RDN downregulated inflammatory cells’ infiltration and the expression of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Next, the potential molecular mechanisms of RDN were predicted through network pharmacology analysis. RDN may ameliorate radiation pneumonitis (RP) by inhibiting AIM2-mediated pyroptosis. Moreover, RDN treatment inhibited EMT and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway. The active compounds from Lonicera japonica Thunb. decreased the phosphorylation of Akt. ConclusionThese findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.

Reduning Injection versus Neuraminidase Inhibitors in the Treatment of Influenza: A Systematic Review and Meta-Analysis.

ObjectiveTo perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza.MethodsThe MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT.ResultsTwelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: −16.20 h, 95% CI: −19.40 to −12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: −4.09 h, 95% CI: −4.22 to −3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: −21.34 h, 95% CI: −41.56 to −1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: −31.83 h, 95% CI: −36.88 to −26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: −28.66 h, 95% CI: −32.23 to −25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe.ConclusionsThis study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.Electronic Supplementary MaterialSupplementary material (Appendixes 1 and 2) are available in the online version of this article at DOI: 10.1007/s11655-022-3524-9.

Comparative Efficacy of Chinese Herbal Injections for Treating Severe Pneumonia: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Severe pneumonia (SP) has a high mortality rate and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of SP treatment. Method: Seven databases were searched from their inception up to April 1, 2021. The methodological quality of included study was evaluated by the Cochrane risk-of-bias tool. Then, a Bayesian network meta-analysis (NMA) was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. A clustering analysis was utilized to compare the effect of CHIs between two different outcomes. Results: A total of 64 eligible randomized controlled trials (RCTs) involving 5,904 participants were identified for this analysis. Six CHIs including Xuebijing injection (XBJ), Tanreqing injection (TRQ), Reduning injection (RDN), Xiyanping injection (XYP), Shenfu injection (SF), and Shenmai injection (SM) were included. The results of the NMA showed that XBJ [odds ratio (OR) = 0.24, 95% credible interval (CI): 0.19, 0.30], TRQ (OR = 0.22, 95% CI: 0.12, 0.37), RDN (OR = 0.29, 95% CI: 0.04, 0.94), and SM (OR = 0.27, 95% CI: 0.08, 0.63) combined with conventional Western medicine (WM) improved the clinical effective rate more significantly than WM alone. Based on SUCRA values, TRQ + WM (SUCRA: 66.4%) ranked the highest in improving the clinical effective rate, second in four different outcomes, and third in only one. According to the cluster analysis, TRQ + WM exerted a positive effect on improving the efficacy of SP. As for safety, less than 30% (18 RCTs) of the included studies reported adverse drug reactions/adverse drug events (ADRs/ADEs), including 14 RCTs of XBJ, 3 RCTs of TRQ, and 1 RCT of RDN. Conclusion: In conclusion, the study found that the CHIs as co-adjuvant therapy could be beneficial for patients with SP. TRQ + WM showed an outstanding improvement in patients with SP considering both the clinical effective rate and other outcomes. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021244587].

Clinical effect of reduning combined with gamma globulin treatment on symptom improvement serum levels of IL-6, 25-(OH)D and LDH in children with severe mycoplasma pneumonia.

Objectives:To investigate the effects of Reduning combined with gamma globulin on symptom improvement and serum levels of interleukin-6 (IL-6), 25-hydroxyvitamin D[25-(OH)D] and lactate dehydrogenase (LDH) in children with severe mycoplasma pneumonia (MP).Methods:A total of 123 children with severe MP admitted to the Changzhou Cancer Hospital affiliated to Soochow University from May 2018 to April 2020 were selected as subjects and randomly divided into three groups: control Group-A, control Group-B and the observation group, with 41 cases in each group. Control Group-A was given with Reduning, control Group-B was treated with gamma globulin, while the observation group was treated with Reduning injection combined with gamma globulin. The clinical efficacy, symptom improvement, incidence of adverse reactions, serum levels of IL-6, 25-(OH)D, LDH, Toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway and T lymphocyte subsets before and after treatment were statistically compared between the three groups.Results:The total effective rate of treatment in the observation group was higher than that in control Group-A and control Group-B (p<0.05); The time for body temperature, lung rales, and cough to return to normal in the observation group was shorter than that in control Group-A and control Group-B (p<0.05). After treatment, the observation group had lower serum levels of IL-6, LDH, and higher levels of 25-(OH)D compared with control Group-A and control Group-B (p<0.05). Moreover, the observation group had lower serum expressions of TLR4 and MyD88 (p<0.05), higher serum levels of CD4+, CD4+/CD8+, and lower CD8+ compared with control Group-A and control Group-B (p<0.05). No significant difference can be seen in the comparison of the incidence of adverse reactions between the three groups (p>0.05).Conclusions:Reduning combined with gamma globulin in the treatment of severe MP is worthy of clinical promotion and application. With such a treatment regimen, the immune function of children with severe MP can be significantly enhanced, the inflammatory response can be suppressed, and symptom improvement can be promoted, further improving the treatment outcome.

Bayesian network Meta-analysis of traditional Chinese medicine injections combined with antiviral western medicine in treatment of influenza

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.

Efficacy and safety of ReDuNing injection as a treatment for COVID-19 and its inhibitory effect against SARS-CoV-2

BackgroundAlthough the rapid emergence of coronavirus disease 2019 (COVID-19) poses a considerable threat to global public health, no specific treatment is available for COVID-19. ReDuNing injection (RDN) is a traditional Chinese medicine known to exert antibacterial, antiviral, antipyretic, and anti-inflammatory effects. In addition, RDN has been recommended in the diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia by the National Health Council and the National Administration of Chinese Medicine. However, there is no information regarding its efficacy against COVID-19. Aim of studyThis study was designed to determine the clinical efficacy of RDN in patients with COVID-19 and characterize its antiviral activity against SARS-CoV-2 in vitro. Materials and methodsA total of 50 adults with COVID-19 were included in this study, and the primary endpoint was recovery from clinical symptoms following 14 days of treatment. General improvements were defined as the disappearance of the major symptoms of infection including fever, fatigue, and cough. The secondary endpoints included the proportion of patients who achieved clinical symptom amelioration on days 7 and 10, time to clinical recovery, time to a negative nucleic acid test result, duration of hospitalization, and time to defervescence. Plaque reduction and cytopathic effect assays were also performed in vitro, and reverse-transcription quantitative PCR was performed to evaluate the expression of inflammatory cytokines (TNF-α, IP-10, MCP-1, IL-6, IFN-α, IFN-γ, IL-2 and CCL-5) during SARS-CoV-2 infection. ResultsThe RDN group exhibited a shorter median time for the resolution of clinical symptoms (120 vs. 220 h, P < 0.0001), less time to a negative PCR test result (215 vs. 310 h, P = 0.0017), shorter hospitalization (14.8 vs. 18.5 days, P = 0.0002), and lower timeframe for defervescence (24.5 vs. 75 h, P = 0.0001) than the control group. In addition, time to improved imaging was also shorter in the RDN group than in the control group (6 vs.8.9 days, P = 0.0273); symptom resolution rates were higher in the RDN group than in the control group at 7 (96.30% vs. 39.13%, P < 0.0001) and 10 days (96.30% vs. 56.52%, P = 0.0008). No allergic reactions or anaphylactic responses were reported in this trial. RDN markedly inhibited SARS-CoV-2 proliferation and viral plaque formation in vitro. In addition, RDN significantly reduced inflammatory cytokine production in infected cells. ConclusionsRDN relieves clinical symptoms in patients with COVID-19 and reduces SARS-CoV-2 infection by regulating inflammatory cytokine-related disorders, suggestion that this medication might be a safe and effective treatment for COVID-19.

Re-Du-Ning injection ameliorates LPS-induced lung injury through inhibiting neutrophil extracellular traps formation

BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and could occur in severe COVID-19 patients. Re-Du-Ning injection (RDN) is a tradition Chinese medicine preparation which has been clinically used for treatment of respiratory diseases including COVID-19. PurposeTo elucidate the potential mechanisms of RDN for the treatment of ALI. MethodsFemale C57BL/6J mice were used to establish ALI model by intraperitoneal injection 10 mg/kg LPS, and RDN injection was intraperitoneally administered with the dose of 5 and 10 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to NETs were analyzed by ELISA, immunofluorescence, Western blotting and network pharmacological approach. ResultsRDN robustly alleviated LPS-induced ALI. Meanwhile, RDN downregulated the expression of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Specifically, RDN treatment inhibited the formation of neutrophil extracellular traps (NETs) and remarkably suppressed the protein of PAD4. The active compound from RDN decreased the phosphorylation of ERK1/2. ConclusionThese findings demonstrate that RDN ameliorates LPS-induced ALI through suppressing MAPK pathway to inhibit the formation of NETs.

Ultrafiltration strategy combined with nanoLC-MS/MS based proteomics for monitoring potential residual proteins in TCMIs

Traditional Chinese medicine injections (TCMIs) containing complex constituents frequently cause unpredictable adverse reactions. The residual heterologous proteins in TCMIs may be one kind of the sensitized constituents. However, few methods were developed to identify and monitor the residual proteins of TCMIs in industry. Here, we described a method combining the advantages of ultrafiltration and mass spectrometry-based proteomics for monitoring the potential residual proteins in Re Du Ning injection (RDNI) intermediates and preparations. We identified and quantified both de novo peptides and the proteins matched against databases of three raw plants by using PEAKS software. Interesting, we found there was a significant decrease of peptides and proteins in No. 3–5 of RDNI intermediates and some even disappeared. Besides, we found this method could greatly reduce the interference of contaminants in proteomics experiments. The rapid and accurate method proposed in this paper could be used for monitoring potential residual proteins in TCMIs to guarantee their quality and safety.

Efficacy of Chinese Herbal Injections for Elderly Patients With pneumonia—A Bayesian Network Meta-analysis of Randomized Control Trials

Background: Pneumonia is a prevalent and complicated disease among adults, elderly people in particular, and the debate on the optimal Chinese herbal injections (CHIs) is ongoing. Our objective is to investigate the comparative effectiveness of various CHIs strategies for elderly patients with pneumonia. Methods: A comprehensive search strategy was executed to identify relevant randomized controlled trials (RCTs) by browsing through several databases from their inception to first, Feb 2020; All of the direct and indirect evidence included was rated by Network meta-analysis under a Bayesian framework. Results: We ultimately identified 34 eligible randomized controlled trials that involved 3,111 elderly participants and investigated 4 CHIs combined with Western medicine (WM) (Xiyanping injection [XYP]+WM, Yanhuning injection [YHN]+WM, Tanreqing injection [TRQ]+WM, Reduning injection [RDN]+WM), contributing 34 direct comparisons between CHIs. Seen from the outcome of Clinical effective rate and time for defervescence, patients taking medicine added with CHIs [Clinical effective rate, XYP + WM(Odd ratio (OR): 0.74, 95%Credible intervals (CrIs):0.55–0.98), YHN + WM(OR: 0.66, 95%CrI: 0.45–0.95), TRQ + WM(OR: 0.65, 95%CrI: 0.50–0.83), RDN + WM(OR: 0.60, 95%CrI: 0.40–0.89); Time for defervescence, YHN + WM(Mean difference (MD): −2.11, 95%CrI: −3.26 to −0.98), XYP + WM(MD: −2.06, 95%CrI: −3.08 to −1.09), RDN + WM(MD: −1.97, 95%CrI: −3.61 to −0.35), TRQ + WM(MD: −1.69, 95%CrI: −2.27 to −1.04)] showed statistically better effect compared with participants in the Control group (CG) who only took WM. Meanwhile, based on the time for disappearance of cough, 3 out of 4 CHIs [TRQ + WM(MD: −2.56, 95%CrI: −3.38 to −1.54), YHN + WM(MD: −2.36, 95%CrI: −3.86 to −1.00) and XYP + WM(MD: −2.21, 95%CrI: −3.72 to −1.10)] strategies indicated improvement of clinical symptoms. Only XYP + WM(MD −1.78, 95%CrI: −3.29 to −0.27) and TRQ + WM (MD: −1.71, 95%CrI: −2.71 to −0.73) could significantly shorten the time for disappearance of pulmonary rales. Conclusion: According to the statistical effect size (The surface under the cumulative ranking), we found that XYP + WM was presumably to be the preferable treatment for treating elderly patients with pneumonia compared with WM alone in terms of clinical effective rate. Our findings were based on very limited evidence and thus should be interpreted with caution. The application of the findings requires further research.

Efficacy and safety of Reduning injection in the treatment of COVID-19: a randomized, multicenter clinical study

Reduning injection is a traditional Chinese medicine (TCM) with known efficacy against a variety of viral infections, but there is no data about its efficacy against coronavirus disease 2019 (COVID-19). To explore the efficacy and safety of Reduning injection in the treatment of COVID-19, a randomized, open-labeled, multicenter, controlled trial was conducted from 12 general hospitals between 2020.02.06 and 2020.03.23. Patients with COVID-19 who met the diagnostic criteria of the "Diagnosis and Treatment Program for Novel Coronavirus Infection Pneumonia (Trial Fifth Edition)". Patients were randomized to routine treatment with or without Reduning injection (20 mL/day for 14 days) (ChiCTR2000029589). The primary endpoint was the rate of achieving clinical symptom recovery on day 14 of treatment. There were 77 and 80 participants in the Reduning and control groups. The symptom resolution rate at 14 days was higher in the Reduning injection than in controls [full-analysis set (FAS): 84.4% vs. 60.0%, P=0.0004]. Compared with controls, the Reduning group showed shorter median time to resolution of the clinical symptoms (143 vs. 313.5 h, P<0.001), shorter to nucleic acid test turning negative (146.5 vs. 255.5 h, P<0.001), shorter hospital stay (14.1 vs. 18.1 days, P<0.001), and shorter time to defervescence (29 vs. 71 h, P<0.001). There was no difference in AEs (3.9% vs. 8.8%, P=0.383). This preliminary trial suggests that Reduning injection might be effective and safe in patients with symptomatic COVID-19.