Traditional Chinese Medicine Injections Research Articles

Tanreqing injection inhibits influenza virus replication by promoting the fusion of autophagosomes with lysosomes: An integrated pharmacological study

Ethnopharmacological relevanceTanreqing injection (TRQ) is widely used, traditional Chinese medicine (TCM) injection used in China to treat respiratory infections. Modern pharmacological studies have confirmed that TRQ can protect against influenza viruses. However, the mechanism by which TRQ inhibits influenza viruses remains unclear. Aim of the studyTo explore the therapeutic effects and possible mechanisms of TRQ inhibition by the influenza virus. Materials and methodsUltra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to determine the chemical composition of TRQ. Isobaric tags for relative and absolute quantification (iTRAQ) were used to define differential proteins related to TRQ inhibition of viruses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. For experimental validation, we established an in vitro model of the influenza virus infection by infecting A549 cells with the virus. The detection of the signaling pathway was carried out through qPCR, western blotting,and immunofluorescence. ResultsFifty one components were identified using UPLC/Q-TOF MS. We confirmed the inhibitory effect of TRQ on influenza virus replication in vitro. Ninety nine differentially expressed proteins related to the inhibitory effect of TRQ were identified using iTRAQ. KEGG functional enrichment analysis showed that the TRQ may inhibit influenza virus replication by affecting autophagy. Through network analysis, 29 targets were selected as major targets, and three key targets, HSPA5, PARP1, and GAPDH, may be the TRQ targets affecting autophagy. In vitro experiments showed that TRQ inhibits influenza virus replication by interfering with the expression and localization of STX17 and VAMP8 proteins, thereby promoting the fusion of autophagosomes with lysosomes. ConclusionTRQ inhibits influenza virus replication by promoting the fusion of autophagosomes with lysosomes. We additionally established potential gene and protein targets which are affected by TRQ. Therefore, our findings provide new therapeutic targets and a foundation further studies on influenza treatment with TRQ.

New approach to heart failure: Integrated traditional Chinese with Western medicine

AbstractHeart failure (HF) is a major global healthcare problem leading to substantial deterioration of prognosis. The current clinical guidelines in HF have begun to emphasize the importance of traditional Chinese medicine (TCM). TCM has been utilized in clinical practice for over 2000 years and is capable of treating a variety of HF pathogenic issues. This review summarizes the classification, pathophysiology, and treatment of HF from three perspectives: Western medicine, TCM, and integrated traditional Chinese and Western medicine (ITCWM). Emphasizing the most recent evidence, this review consolidates knowledge on ITCWM treatments for HF pertaining to different TCM syndromes, including TCM decoctions, oral patent Chinese medicine, TCM injections, as well as therapies like acupuncture and moxibustion. Additionally, this review explores TCM approaches to HF prevention, such as tai chi, Baduanjin exercise, and Sanfu acupoint herbal patching. The findings of this study suggest that ITCWM holds promise for the treatment and rehabilitation of HF. However, further research is warranted to elucidate the underlying mechanisms.

Clinical characteristics and risk factors analysis of 505 cases of infusion reactions in a tertiary hospital.

Background: The clinical characteristics and risk factors of infusion reactions (IRs) are inadequately described in clinical practice due to underreported cases. In the present study, we reported the current status of IRs based on an in-hospital pharmacovigilance database of a tertiary care hospital. Methods: Our study conducted a retrospective analysis of drug-induced IRs recorded at an in-hospital pharmacovigilance center between January 2015 to December 2019. The descriptive statistical analysis encompassed main causative agents, clinical manifestations, organ/system involvement and outcome. The severity of IRs was assessed with reference to the CTCAE version 5.0 criteria and we investigated risk factors associated with severe IRs. Results: During the study period, a total of 505 cases of inpatient drug-induced IRs were detected, of which 79.2% (400 cases) were classified as general IRs and 20.8% (105 cases) were categorized as severe IRs. The primary drugs responsible for these reactions were antibiotics (23%, 116 cases), with piperacillin sodium-sulbactam sodium being the most prevalent, followed by antineoplastic agents (18.4%, 93 cases) and traditional Chinese medicine injections (TCMIs) (12.9%, 65 cases). The administration of cefoperazone - sulbactam, mannatide, Shenqi Fuzheng, elemene, and diterpene ginkgolides meglumine resulted in a higher incidence of critical IRs. Among all cases of IRs, 43.2%, 41.2%, and 23.4% showed signs and symptoms of circulation, skin mucosa, and respiratory organs/systems, respectively. 9.1% of cases experienced systemic damage, while 7.1% and 5.9% of cases reported neurological and gastrointestinal related adverse reactions, respectively. The multivariate analysis revealed that alcohol consumption (OR = 2.389%, 95% CI 1.141-5.002, p = 0.021), age over 65 (OR = 1.814%, 95% CI 1.052-3.127, p = 0.032) and the utilization of contrast media (OR = 4.072%, 95% CI 1.903-8.713, p < 0.001) were identified as risk factors for the development of severe IRs. Conclusion: Understanding the clinical characteristics of IRs helps to implement effective pharmaceutical monitoring and appropriate preventive measures for susceptible populations with risk factors.

A novel method for evaluating pseudoallergy based on β-hexosaminidase and its application for traditional Chinese medicine injections.

Pseudoallergy is a typical and common adverse drug reaction to injections, especially in traditional Chinese medicine injections (TCMIs). At present, the evaluation methods for pseudoallergy include cell methods in vitro and animal methods in vivo. The mast cell evaluation method based on the β-hexosaminidase (β-Hex)-catalyzed substrate, 4-nitrophenyl-β-N-acetyl-D-glucosaminide (4-NPG), is an important method for the evaluation of drug-induced pseudoallergy, but it is prone to false positive results and has insufficient sensitivity. In this study, a novel β-Hex evaluation system with rat basophilic leukemia-2H3 cells based on high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was established, which effectively increased the sensitivity and avoided false positive results. Cell viabilities were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. In addition, a method for the determination of histamine, which is another indicator in the development of pseudoallergy, was established to validate the above method. The results of this novel method indicated that two TCMIs (Shuxuening injection and Shenqi Fuzheng injection), which were considered to be pseudoallergenic using 4-NPG, were not pseudoallergenic. Overall, the novel β-Hex/HPLC-FLD evaluation system using Rat basophilic leukemia-2H3 cells established was effective and precise. It could be used for the evaluation of pseudoallergic reactions caused by TCMIs and other injections.

Comparative efficacy of five traditional Chinese medicine injections for treating heart failure with reduced and mildly reduced ejection fraction: Bayesian network meta-analysis

BackgroundMore than half of all heart failure (HF) patients have heart failure with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF). The combination of traditional Chinese medicine injections (TCMIs) with Western medicine treatment (WMT) has been reported to have better efficacy than using WMT alone. However, the positive effects of TCMIs combined with WMT on HFrEF and HFmrEF require more comprehensive and systematic evidence and warrant further investigation. MethodsThe NMA searched eight databases, including four English and four Chinese, from database creation to November 10, 2022. We used the Cochrane Risk of Bias tool (ROB 2) to assess the selected studies' quality. OpenBUGS and STATA 17.0 were used for network meta-analysis. ResultsThe 101 RCTs were included in the systematic review. Studies have shown that when combined with any of the five TCMIs, WMT was more efficient than WMT alone. Shenmai injection (SMI) + WMT may be the best treatment for clinical effectiveness rate (CER) improvement and b-type natriuretic peptide (BNP) reduction. Huangqi injection (HQI) + WMT was the best treatment for improving left ventricular ejection fraction (LVEF). Danhong injection (DHI) + WMT may be the best treatment for lowering left ventricular end-diastolic dimension (LVEDD). Xinmailong injection (XMLI) + WMT was likely the best treatment for increasing the 6-min walking test (6MWT). In addition, XMLI had the lowest incidence of adverse reactions (3.38%). ConclusionsShenfu injection (SFI), SMI, DHI, XMLI, and HQI combined with WMT have stronger efficiency in treating HFrEF and HFmrEF. However, as all studies were conducted in China, this review is limited by the inevitable selection bias, and further high-quality multicenter randomized controlled trials (RCTs) are required.

Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) &gt; Yiqi Fumai Injection+conventional treatment(57.1%) &gt; Xuebijing Injection+conventional treatment(56.6%) &gt; Shenmai Injection+conventional treatment(53.1%) &gt; Shenfu Injection+conventional treatment(45.3%) &gt; conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) &gt; Shenmai Injection+conventional treatment(69.6%) &gt; Shenfu Injection+conventional treatment(62.7%) &gt; Xinmailong Injection+conventional treatment(61.6%) &gt; Shuxuening Injection+conventional treatment(54.8%) &gt; Shenqi Fuzheng Injection+conventional treatment(46.7%) &gt; Shengmai Injection+conventional treatment(45.9%) &gt; Breviscapine Injection+conventional treatment(39.9%) &gt; Danhong Injection+conventional treatment(38.8%) &gt; Huangqi Injection+conventional treatment(38.7%) &gt; conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) &gt; Shenmai Injection+conventional treatment(57.7%) &gt; Shenfu Injection+conventional treatment(52.5%) &gt; Shengmai Injection+conventional treatment(30.1%) &gt; conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) &gt; Yiqi Fumai Injection+conventional treatment(61.5%) &gt; Shenfu Injection+conventional treatment(51.2%) &gt; Shengmai Injection+conventional treatment(48.1%) &gt; Xinmailong Injection+conventional treatment(26.6%) &gt; conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) &gt; Xinmailong Injection+conventional treatment(68.1%) &gt; Shenfu Injection+conventional treatment(63.1%) &gt; Xuebijing Injection+conventional treatment(56.7%) &gt; Shengmai Injection+conventional treatment(51.1%) &gt; Shenqi Fuzheng Injection+conventional treatment(42.8%) &gt; Huangqi Injection+conventional treatment(34.7%) &gt; conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.

Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

Fuling Guizhi Baizhu Gancao Decoction combined with traditional Chinese medicine and acupoint injection in the treatment of refractory ascites in patients with hepatitis B-related cirrhosis.

Fuling Guizhi Baizhu Gancao Decoction combined with traditional Chinese medicine and acupoint injection in the treatment of refractory ascites in patients with hepatitis B-related cirrhosis.

An Online CMC–LC/MS Method for Screening Angiogenesis Promoting Components in Yiqi Fumai Lyophilization Injection (YQFM)

Objective In this study, an online CMC–LC/MS method was established in order to screen the active components of Yiqi Fumai lyophilization injection (YQFM) related to angiogenesis. The pro-angiogenic active components of YQFM were screened using this system and were then further verified. Methods The ECV304/CMC model coupled online with an HPLC–MS system was initially developed to screen, analyze, and identify the allergenic components of YQFM. A fraction was retained on the ECV304/CMC column, which was identified as ginsenoside Rb2. A cell proliferation assay and zebrafish intestinal microvascular model labeled with green fluorescence were used to detect the proliferation effect of ginsenoside Rb2. Results (1) The active component in YQFM, which was retained on the column, was ginsenoside Rb2. (2) Within a concentration range of 2.5–20 μg/mL, ginsenoside Rb2 was shown to promote the proliferation of ECV304 and EPCs cells and increase the area of sub-intestinal vessels in zebrafish. Conclusion Ginsenoside Rb2, the active component in YQFM, can promote angiogenesis. The ECV304/CMC-online-HPLC system may serve as an effective screening tool for the vasoactive components from the traditional Chinese medicine injection.

Involvement of p38 MAPK/cPLA2 and arachidonic acid metabolic pathway in Shengmai injection-induced pseudo-allergic reactions.

Adverse reactions to traditional Chinese medicine injections involve pseudo-allergic reactions (PARs). However, in clinical practice, "immediate allergic reactions" and PARs in response to these injections are not often differentiated. This study aimed to clarify the type of reactions produced by Shengmai injections (SMI) and elucidate the possible mechanism. A mouse model was used to evaluate vascular permeability. Metabolomic and arachidonic acid metabolite (AAM) analyses were performed using UPLC-MS/MS, and the p38 MAPK/cPLA2 pathway was detected by western blotting. The first exposure to intravenous SMI rapidly and dose-dependently induced edema and exudative reactions in the ears and lungs. These reactions were not IgE-dependent and were likely to be PARs. Metabolomic analysis showed that endogenous substances were perturbed in SMI-treated mice, in which the arachidonic acid (AA) metabolic pathway was the most affected. SMI substantially increased the levels of AAMs in lung, including prostaglandins (PGs), leukotrienes (LTs), and hydroxy-eicosatetraenoic acids (HETEs). The p38 MAPK/cPLA2 signaling pathway was activated after a single SMI dose. Inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes reduced exudation and inflammation in the ears and lungs of mice. Production of inflammatory factors that increase vascular permeability may result in SMI-induced PARs, and p38 MAPK/cPLA2 signaling pathway and downstream AA metabolic pathway are involved in the reactions.

Discussion of Acute Deficiency Syndrome Theory and its Clinical Application

Discussion of Acute Deficiency Syndrome Theory and its Clinical Application

Network meta-analysis of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment.

This study conducted a network meta-analysis to comprehensively compare the efficacy and safety of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment. We searched relevant previous studies from databases including Pubmed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinMed), VIP, and Wanfang Database. The searched studies spanned from the inception of databases to December 2022. The included randomized controlled trials were screened; data were extracted; and bias risk was assessed. The network meta-analysis was performed using Revman 5.4 software, R software, and STATA software. Fifty randomized controlled studies were included, including 8 types of traditional Chinese medicine injection. The results showed that Aidi injection [OR 1.65,95%CI (1.33,2.05)], compound Kushenshen injection [OR 2.72,95%CI (2.12,3.51)], Kangai injection [OR 2.16,95%CI (1.56,3.02)], and Shenqi Fuzheng injection [OR 1.97,95%CI (1.24,3.15)] combined with chemotherapy in colorectal cancer treatment had a significantly higher objective response rate (p < 0.05) than single chemotherapy, and compound Kushen injection + chemotherapy [OR 2.72,95%CI (2.12,3.51)] regimen ranked the highest. The disease control rate of Aidi injection, Brucea javanica oil emulsion injection [OR 4.1,95%CI (1.74,10.43)], compound Kushen injection [OR 2.43,95%CI (1.73,3.44), Kangai injection[OR 2.31,95%CI (1.51,3.58)], Kanglaite injection[OR 3.18,95%CI (1.52,6.9)], and Shenqi Fuzheng injection[OR 2.6,95%CI (1.22,5.92)] combined with chemotherapy in the treatment of colorectal cancer was significantly improved (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy[OR 4.1,95%CI (1.74,10.43)] regimen ranked the highest. The incidence of leukopenia reduction in the treatment of colorectal cancer was significantly reduced by Aidi injection[OR 0.32,95%CI (0.24,0.43)], Brucea javanica oil emulsion injection [OR 0.34,95%CI (0.17,0.68)] compound Kushen injection [OR 0.27,95%CI (0.17,0.40)], Kangai injection [OR 0.23,95%CI (0.14,0.37)], and Kanglaite injection [OR 0.20,95%CI (0.09,0.45)] combined with chemotherapy (p < 0.05), and Kanglaite injection + chemotherapy [OR 0.20,95%CI (0.09,0.45)] regimen ranked the highest. Aidi injection [OR 0.48,95%CI (0.3,0.74)], Brucea javanica oil emulsion injection [OR 0.09,95%CI (0.01,0.43)], and Kangai injection [OR 0.47,95%CI (0.22,0.96)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of thrombocytopenia reduction (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy [OR 0.09,95%CI (0.01,0.43)] regimen ranked the highest. Aidi injection [OR 0.49,95%CI (0.32, 0.74)], Kangai injection [OR 0.26,95%CI (0.09,0.71)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of hemoglobin reduction (p < 0.05), and Kangai injection + chemotherapy [OR 0.26,95%CI (0.09,0.71)] regimen ranked the highest. Aidi injection [OR 0.38,95%CI (0.28,0.52)], compound Kushen injection [OR 0.23,95%CI (0.15,0.36)] and Kangai injection [OR 0.19,95%CI (0.12,0.30)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of nausea and vomiting (p < 0.05), and Kangai injection + chemotherapy[OR 0.19,95%CI (0.12,0.30)] regimen ranked the highest. Aidi injection [OR 0.51,95%CI (0.35,0.74)], compound Kushenshen injection [OR 0.27,95%CI (0.15,0.47)], and Kanglaite injection [OR 0.31,95%CI (0.13,0.69)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of abdominal pain and diarrhea (p < 0.05), and compound Kushen injection + chemotherapy [OR 0.27,95%CI (0.15,0.47)] regimen ranked the highest. Aidi injection, Brucea javanica oil emulsion injection, compound Kushen injection, Kangai injection, Shenqi Fuzheng injection, Kanglaite injection, Shenfu injection, and Xiaoaiping injection combined with chemotherapy functioned more effectively than single chemotherapy did in colorectal cancer treatment. Nevertheless, limited by the treatment quality and methodology of different intervention measures included in the study, this conclusion is expected to be scrutinized in higher-quality and rigorously designed randomized controlled trials. PROSPERO registration No.: CRD42023392398.

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine.

Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway

Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis

IntroductionAidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). ObjectivesWe performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. MethodologyAll randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. ResultsAll 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. ConclusionsCurrent evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

On-line screening and verification of haptens in Xiangdan injection combining chemical analysis with activity detection

Xiangdan injection (XDI), as a well-known traditional Chinese medicine injection, is of great significance to treat cardiovascular and cerebrovascular diseases. The haptens causing allergic reactions are urged to be detected due to the adverse reaction. In this study, an efficient approach was established to rapidly identify and screen potential haptens in XDI for the first time by combining high performance liquid chromatography-diode array detector-electrospray ionization-ion trap-time of flight-mass spectrometry with human serum albumin-fluorescence detector (HPLC-DAD-ESI-IT-TOF-MS-HSA-FLD). 21 compounds were identified according to their mass spectrum or comparison with reference substances and 8 salvianolic acids in XDI showed interactions with HSA in varying degrees. After that, surface plasmon resonance (SPR) was applied to screen the compounds showing specific affinity with human serum albumin (HSA). Subsequently, active systemic anaphylaxis (ASA) in guinea pigs was carried out to verify the sensitization of active compounds, In the meantime the serum IgE level before and after challenge was measured by the enzyme-linked immunosorbent assay (ELISA). Ultimately, it was tested that salvianolic acid C had a strong sensitization, in addition, lithospermic acid, rosmarinic acid and salvianolic acid B had potential sensitization. This study suggest that the on-line method provides rapid preliminary searching for haptens in XDI, combined with SPR and ASA, offering an efficient, rapid and comprehensive approach to screen haptens.

Magnetic Ti3C2 MXene Nanosheets Prepared for Enrichment of Phosphopeptides

MXenes have received lots of attention since discovered and have been applied in various fields. In this work, Ti3C2-Fe3O4 composites with exposed non-modified Ti3C2 MXene nanosheets were designed and prepared by an in situ growth strategy and then applied in the enrichment of phosphopeptides. The two-dimensional composites could interact with the phosphopeptides through a metal oxide affinity chromatography mechanism provided by Ti-O and Fe-O bonds and a hydrophilic interaction chromatography mechanism by surface hydroxyl groups. This magnetic nanomaterial with a specific surface area of 66.1 m2·g-1 had high sensitivity to phosphopeptides (0.5 nmol·L-1) and high selectivity (1:1000 of the molar ratio of β-casein to bovine serum albumin). Non-fat milk was adopted as a real sample to preliminarily examine the applicability of the Ti3C2-Fe3O4-based protocol. Subsequently, Qingkailing injection, a kind of traditional Chinese medicine injection, was introduced to further explore the suitability of the nanocomposites for phosphopeptide enrichment from more complex matrices and satisfactory results were obtained.

Active compounds and potential targets of Shuganning injection in the treatment of hepatocellular carcinoma by network pharmacology and in vitro validation.

Shuganning injection (SGNI), a TCM (traditional Chinese medicine) injection with good hepatoprotective effects, exerted therapeutic effects on hepatocellular carcinoma (HCC). However, the active compounds and effects of SGNI on HCC remain unclear. The objective of this study was to investigate the active compounds and potential targets of SGNI in the treatment of HCC, and explore the molecular mechanisms of main compounds. Network pharmacology was applied to predict the active compounds and targets of SGNI on cancer. The interactions between active compounds and target proteins were validated by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and pull-down assay. The in vitro test of the effects and mechanism of vanillin and baicalein was elucidated by MTT, western blot, immunofluorescence, and apoptosis analysis. According to compound characteristics, targets, etc., two typical active ingredients (vanillin and baicalein) were selected as representatives to explore the effects on HCC. Vanillin (an important food additive) bound to NF-κB1 and baicalein (a bioactive flavonoid) bound to FLT3 (FMS-like tyrosine kinase 3) were confirmed in this study. Vanillin and baicalein both inhibited cell viability and promoted apoptosis of Hep3B and Huh7 cells. In addition, both vanillin and baicalein could enhance the activation of the p38/MAPK (mitogen-activated protein kinase) signaling pathway, which may partially explain the anti-apoptosis effects of the two compounds. In conclusion, two active compounds of SGNI, vanillin and baicalein, promoted apoptosis of HCC cells via binding with NF-κB1 or FLT3, and regulating the p38/MAPK pathway. Baicalein and vanillin may be good candidates for HCC treatment on drug development.

5-Hydroxymethylfurfural multimers induce pseudo-allergic reaction through FcεRI at high doses.

Under acidic and high temperature conditions, 5-hydroxymethylfurfural (5-HMF) converted from sugar further produces dimers (Compound II) and trimers (Compound III). The polymers were less reported, and sensitization effect of them was reported in this study. Compounds II and III induced the local and systemic anaphylaxis effect in passive cutaneous anaphylaxis mice model and activated RBL-2H3 cell inducing [Ca2+ ] mobilization, resulting in the release of β-hexosaminidase and histamine in vitro. The gene knockdown assay figured out that Compounds II and III induced degranulation through FcεRI. Further, Compounds II and III had a certain affinity with FcεRI by cell membrane chromatography and may combine on the "proline sandwich" structure indicated by molecular docking. All above suggested Compounds II and III can induce pseudo-allergic reaction through FcεRI in vivo and in vitro. Our work provides basic research to prove that the newly discovered 5-HMF transformants, Compounds II and III, induce pseudo-allergic reaction in vitro and in vivo through FcεRI, which is different pathway from 5-HMF. In foods with high sugar content, the sensitization of Compounds II and III needs more attention. In high-sugar foods and medicines, especially traditional Chinese medicine injections, the content of transformants needs to be detected.

Systematic analysis of the role and significance of target genes of active ingredients of traditional Chinese medicine injections in the progression and immune microenvironment of hepatocellular carcinoma.

Background: Traditional Chinese medicine in China is an important adjuvant therapy for the treatment of hepatocellular carcinoma (HCC) and traditional Chinese medicines injections have a wide range of clinical applications. The purpose of this study was to identify the active ingredients and related genes of traditional Chinese medicine injections that can treat hepatocellular carcinoma. Methods: Effective small molecule components were extracted from 14 types of traditional Chinese medicines from 8 injections and the main gene targets were identified. The 968 patients with HCC were classified based on the target gene set, and the characteristics of patients with different subtypes were analyzed. Patients with two subtypes of HCC were compared with normal tissues and cirrhosis to identify important gene targets related to traditional Chinese medicines in HCC progression. Results: In this study, 138 important genes associated with traditional Chinese medicines were identified and two HCC subtypes were identified. By analyzing the differences between the two subtypes, 25 related genes were associated with HCC subtypes. Through clinical and pharmacological analysis, this study identified quercetin as an important traditional Chinese medicines small molecule and secreted phosphoprotein 1 (SPP1) as an important oncogene in HCC. Conclusion: Traditional Chinese medicines injection is an important adjuvant treatment modality for HCC. SPP1 is an important oncogene in HCC.