Efficacy of Daiwenjiu ointment on the treatment of cervical spondylosis with nerve root type caused by cold dampness obstruction.

OBJECTIVE: This study aimed to assess the clinical efficacy of Daiwenjiu ointment in the treatment of cervical spondylosis with cold dampness obstruction nerve root type. METHODS: A retrospective analysis was conducted on a cohort of 110 patients diagnosed with cervical spondylotic radiculopathy. Based on the treatment method, the patients were divided into two groups. The control group received electroacupuncture treatment, while the observation group received a combination of Daiwenjiu ointment and electroacupuncture treatment. The outcome measures included Japanese Orthopedic Association (JOA) scores for cervical spine function, Simplified McGill Pain Questionnaire (SF-MPQ) scores, and changes in serum inflammatory factors TNF-α and IL-1ß. RESULTS: Following treatment, the JOA score in the observation group increased from 9.45 ± 1.35 to 14.82 ± 1.29 after treatment, indicating better recovery of cervical spine function compared to the control group (p < 0.001). The SF-MPQ score in the observation group decreased to 18.25 ± 3.80 after treatment, while it remained at 30.20 ± 4.30 in the control group. This difference between the groups was statistically significant (p < 0.001). Furthermore, the observation group demonstrated a significant decrease in serum levels of TNF-α and IL-1ß after treatment compared to the control group (p < 0.001). CONCLUSION: Daiwenjiu ointment exhibits significant therapeutic effects in patients with cold dampness obstruction nerve root type cervical spondylosis. It effectively improves cervical function, reduces pain, and downregulates inflammatory cytokine levels.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.

Construction of a core outcome set in clinical research of acupuncture and moxibustion for treatment of adhesive capsulitis / 中国针灸

This study aims to construct the core outcome set for the clinical trials of adhesive capsulitis treated with acupuncture and moxibustion. Using systematic review, semi-structured interview, Delphi questionnaire survey, analytic hierarchy process and expert consensus meeting, the primary outcomes are obtained, i.e. local tenderness, pain degree during movement, range of motion, changes in range of motion, function score, and score of local symptoms of shoulder joint. The secondary outcomes are myofascial thickness, thickness of the inferior wall of the joint capsule, health status, activity of daily living, incidence of adverse events, laboratory indexes, vital signs, cost-effectiveness, total effective rate, and patient satisfaction. It is expected to provide a reference for the outcome selection in clinical trials and the generation of medical evidences in the treatment of adhesive capsulitis with acupuncture and moxibustion.

A multifunctional black phosphorus-based adhesive patch intrinsically induces partial EMT for effective burn wound healing.

The ultimate goal of cutaneous wound healing is to reform a stratified epithelium to restore the normal epidermal barrier, which involves the epithelial-to-mesenchymal transition (EMT) process. However, healing strategies based on EMT induction are immature and ambiguous to date. Excessive induction of EMT may cause fibrosis, hypertrophic scarring, and increased risk of malignancy. Here, we present a new EMT-inducing strategy for eliciting partial EMT to facilitate proper epithelial cell migration. The new EMT-inducing system integrates black phosphorus nanosheets (BPNSs), catechol-modified chitosan (CA-CS), and oxidized dextran (Odex) to engineer an adhesive hydrogel patch (C&BP-Patch) with remarkable efficacy on infectious burn wound healing. The C&BP-Patch can orchestrate key early skin wound healing processes including hemostasis, inflammation, and proliferation, which enable fast partial EMT induction to restore an intact epithelial barrier. The C&BP-Patch acts initially as a high-performance bio-sealant to create a moist and stable microenvironment for EMT. Moreover, the photothermal effects of the C&BP-Patch can eliminate bacteria, accelerate microcirculation and reduce inflammation to maintain a proper EMT. Most importantly, the BPNSs can intrinsically induce partial EMT of epithelial cells via a Snail1-mediated signaling pathway. Therefore, our study proposes a new strategy for effective infectious burn wound healing based on inducing partial EMT.

A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

Herbal Textual Research on Myrrha in Famous Classical Formulas / 中国实验方剂学杂志

In order to provide the basis for the development of famous classical formulas containing Myrrha， the name， origin， quality evaluation， harvest and processing of Myrrha were systematically researched by consulting the ancient herbal and medical books， combining with the modern related literature. According to textual research， the results showed that Commiphora myrrha was the main base in ancient times， which was produced in Somalia， Ethiopia and northern Kenya. In addition， raw and fried products of Myrrha were the commonly used specifications in ancient herbal medicine， which are still used today. Nowadays， Myrrha， fried Myrrha and vinegar-processed Myrrha were the commonly used specifications. Among the three specifications， Myrrha is the raw products after cleaning， fried Myrrha is a kind of processed products， which has relevant records in ancient materia medica and is still used today. Vinegar-processed Myrrha is a new processing specification in modern times. Based on the research results， it is suggested that Myrrha in Shentong Zhuyutang should be the purified raw Myrrha in accordance with the 2020 edition of Chinese Pharmacopoeia.

Chinese Herbal Prescription Against Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer is a type of upper gastrointestinal malignant tumor with a high degree of malignancy， strong invasion ability， and poor prognosis， which belongs to the category of "dysphagia" in traditional Chinese medicine （TCM）. In addition to tumor resistance， Chinese herbal prescription plays a role in sensitization. In light of information in literature， the syndrome elements of esophageal cancer include Qi stagnation， phlegm， Qi deficiency， blood stasis， and Yin deficiency. After clinical differentiation， the syndromes of esophageal cancer are divided into phlegm and Qi obstruction， Qi and Yin deficiency， fluid deficiency and heat accumulation， Qi deficiency and phlegm dampness， combined phlegm and heat， combined phlegm and stasis， combined heat toxin and stasis， healthy Qi deficiency and toxin accumulation， et al. Dabanxiatang， Qigesan， Xuanfu Daizhetang， Liujunzitang， Shashen Maidongtang， and Tongyoutang are the common clinical prescriptions， where Qigesan， Liu Junzitang， and Tongyoutang have been proved by in vitro and in vivo experiments to exert anti-esophageal cancer effect by directly inhibiting tumor cell proliferation， promoting apoptosis， affecting tumor microenvironment， regulating cell energy metabolism， and inhibiting angiogenesis. In addition， an increasing number of studies have been conducted on anti-esophageal cancer effect of Chinese herbal prescription by targeting non-coding single-stranded microRNA. The specific mechanisms of Da Banxiatang， Shenzhe Peiqitang， Xiao Xianxiongtang， Renshen Banxiatang， and Liushenwan have been scarcely reported despite good clinical efficacy. Wuzhuyu Tang and Tongguansan recorded in ancient books have been rarely applied in modern times. Therefore， the present study reviewed the special drugs and prescriptions mentioned in ancient TCM classics， the commonly used Chinese herbal prescriptions in modern clinical practice， and experimental research progress， to promote treatment methods of Chinese herbal prescriptions against esophageal cancer.

Efficacy of add-on Danhong injection in patients with unstable angina pectoris: A double-blind, randomized, placebo-controlled, multicenter clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI)，which is extracted from Salviae miltiorrhizae and Flos carthami，has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. AIM OF THE STUDY: To determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. RESULTS: 160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97-81.09%] and 54.34% [95% CI, 42.68-65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. CONCLUSIONS: A small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study.

OBJECTIVE: To identify differentially expressed proteins (DEPs) in sera of patients with chronic atrophic gastritis (CAG) using isobaric tags for relative and absolute quantitation (iTRAQ) and to explore acupuncture's mechanism in CAG. METHODS: Peripheral sera from 8 healthy volunteers (HC), 8 chronic nonatrophic gastritis (NAG) patients, 8 CAG patients, and 8 CAG patients who underwent acupuncture treatment (CAG + ACU) were collected followed by labeling with iTRAQ reagent for protein identification and quantification using two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). Representative DEPs were selected through bioinformatics, and proteins were verified by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 4,448 unique peptides were identified, corresponding to 816 nonredundant proteins. A 1.4-fold difference was used as the threshold. Compared with the HC group, 75 and 106 DEPs were identified from CAG and NAG groups, respectively. Compared with the CAG group, 110 and 66 DEPs were identified from the NAG and CAG + ACU groups, respectively. The DEPs were mainly involved in protein binding and the Notch signaling pathway-related proteins, and the upregulated proteins included actin-binding proteins (thymosin beta-4, tropomyosin-4, profilin-1, transgelin-2), while the downregulated proteins included Notch2 and Notch3. After acupuncture, the expression of these proteins in CAG patients was less differentiated from that in healthy people. The level of the above 6 proteins were verified by ELISA, and the results were similar to the results of iTRAQ analysis. CONCLUSIONS: Actin-binding proteins and Notch signaling pathway-related proteins were correlated with the development and progression of CAG and thus are potential diagnostic markers for CAG. Acupuncture may play a role in regulating actin-binding proteins and Notch signaling pathway-related proteins to play a therapeutic role in CAG.

[Effect of traditional Chinese medicine in improving human health by regulating bacterial quorum sensing system].

Quorum sensing(QS) is one of the research hotspots in the fields of microbiology and medicine in recent years. Quorum sensing is a cell communication regulatory system, which is used by bacterial flora to pass on information of population density by sensing specific signaling molecules to the environment. The QS system of bacteria can impact biological functions, such as bacterial growth, proliferation, biofilm formation, virulence factor production, antibiotic synthesis, and ultimately adapt the bacteria to environmental changes. At present, more and more active ingredients can regulate quorum sensing have been found in traditional Chinese medicines(TCM). TCM and their active ingredients can promote the growth of beneficial bacteria, inhibit the proliferation of pathogenic bacteria and finally achieve the purpose of treating diseases. It embodies multi-pathway and multi-target characteristics of traditional Chinese medicine. This article first introduces molecular types and regulation mechanisms of quorum sensing signals between bacteria. On this basis, the human health-related bacterial quorum sensing is summarized, and the regulatory effect of TCM on bacterial quorum sensing system is discussed. Finally, it is noted that the material basis and mechanisms of TCM in improving human health through bacterial quorum sensing system are still unclear. Future research hotspots will focus on quorum sensing active substances, quorum sensing key nodes and relevant targets. In a word, this article provides reference for the treatment of relevant diseases.

Intracellular pH-propelled assembly of smart carbon nanodots and selective photothermal therapy for cancer cells.

A kind of smart carbon nanodots (CNDs) with the pH response feature was prepared by the one-pot hydrothermal treatment of citric acid and dicyandiamide, which was used for the differentiation of cancer/normal cells and the selective photothermal therapy (PTT) of cancer cells. When the smart CNDs were cultured with cells, they were highly internalized in the lysosomes of cells. Since the small-sized CNDs (about 5 nm) tends to form aggregation (as large as about 20 nm or even larger) under an acid condition (pH = 4.7) due to the electrostatic attraction produced by the surface protonation, relatively severer aggregation of the CNDs were observed in liver cancer cells (HepG2 cells) relative to normal ones (LO2 cells) due to a relative lower pH in the lysosomes of HepG2 cells, which endows them a new strong absorption band at longer wavelengths (450-900 nm) and a higher photothermal conversion efficiency (42.13 %), benefiting to differentiated PTT. The flow cytometric data indicates strong photothermal ablation (8 min, 509.6 mW/cm2) for cancer cells with the assistance of these smart CNDs achieves 82 % death rate of cancer cells, while much less damage is observed on the normal cells (6.35 %). To the best of our knowledge, this is the first report about CNDs for selective PTT owing to their intrinsic property without the aid of any other targeting ligands. These smart CNDs are also available for other acid-responsive sensing systems, and this study inspires us in the synthesis of near-infrared featured carbon materials.

NF-κB inhibition promotes apoptosis in androgen-independent prostate cancer cells by the photothermal effect via the IκBα/AR signaling pathway.

The photothermal response of nanomaterials provides a basis for many biomedical applications, including diagnosis (e.g., biosensor and photoacoustic imaging) and treatment (e.g., drug delivery and photothermal therapy). The use of nano-materials for cancer phototherapy (solid tumor ablation) can cause cell necrosis and apoptosis. However, photothermal effects using the same material can differ among tumor cell types, and the molecular mechanisms underlying these differences are not clear. We used polydopamine (PDA)-coated branched Au-Ag nanoparticles (Au-Ag@PDA NPs) for the photothermal treatment of two prostate cancer cell lines. The therapeutic effect was evaluated by CCK8, flow cytometry, and expression analyses of related genes by western blotting. Photothermal therapy resulted in oxidative stress in prostate cancer cells and activated the mitochondrial-related apoptosis pathway, increasing the Bax expression. In addition, we observed a greater photothermal treatment effect on the androgen-dependent cells LNCaP than the androgen-independent cells DU145. Pretreatment with an inhibitor of the NF-κB signaling pathway (BAY 11-7082) enhanced the expression of BAX in the DU145 cells and increased the sensitivity of the cells to the heat treatment of Au-Ag@PDA NPs both in vitro and in vivo. Our findings explain the differences in the observed effects of photothermal therapy and provide the direction for further improvements to this strategy.

Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways.

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 µg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.

Pharmacokinetic mechanisms underlying the detoxification effect of Glycyrrhizae Radix et Rhizoma (Gancao): drug metabolizing enzymes, transporters, and beyond.

INTRODUCTION: Glycyrrhizae Radix et Rhizoma (Gancao in Chinese) is the most frequently used traditional Chinese medicine (TCM) owing to its various pharmacological effects and, more importantly, the synergistic effects that enhance the efficacy and reduce the toxicity of other TCMs. Areas covered: We reviewed publications, predominantly between 1990 and 2018, that examined pharmacokinetic interactions between Gancao and other TCMs, or the bioactive constituents of these TCMs. This review focuses on the underlying mechanisms and the components responsible for the pharmacokinetic modulation by Gancao. Expert opinion: In general, the pharmacokinetic effects of Gancao are a result of its constituents such as macromolecules, like proteins, and small molecules, such as saponins and flavonoids. The mechanisms are related to formation of complexes and the influence of these on drug solubility, permeability, distribution, and metabolism. The detoxification effect of a single dose of Gancao is mainly mediated by the suppression of the intestinal absorption of toxic constituents of the co-administered TCMs and is attributable to constituents that form complexes with the toxic compounds and cause them to sediment. In contrast, the detoxification effects of repeated doses of Gancao are mediated mainly via the induction of drug metabolizing enzymes and efflux transporters.

Synthesis of ginsenoside Re-based carbon dots applied for bioimaging and effective inhibition of cancer cells.

BACKGROUND: Fluorescent carbon-based nanomaterials have promising properties such as biosensing, cell imaging, tracing and drug delivery. However, carbon dots (CDs) with specific inherent biological functions have not been investigated. Ginsenosides are the components with multiple bioactivities found in plants of the genus Panax, which have attracted a lot of attention for their anticancer effect. MATERIALS AND METHODS: In this study, we prepared a kind of novel photoluminescent CDs from ginsenoside Re by one-step hydrothermal synthesis method. The conventional methods including transmission electron microscopy, Fourier transform infrared spectroscopy, HPLC and fluorescence spectrum were used for characterization of CDs. In vitro anticancer effect was investigated by cytotoxicity assay, flow cytometry and Western blot analysis. RESULTS: The as-prepared Re-CDs had an average diameter of 4.6±0.6 nm and excellent luminescent properties. Cellular uptake of Re-CDs was facilitated by their tiny nanosize, with evidence of their bright excitation-dependent fluorescent images. Compared with ginsenoside Re, the Re-CDs showed greater inhibition efficiency of cancer cell proliferation, with lower toxicity to the normal cells. The anticancer activity of Re-CDs was suggested to be associated with the generation of large amount of ROS and the caspase-3 related cell apoptosis. CONCLUSION: Hopefully, the dual functional Re-CDs, which could both exhibit bioimaging and anticancer effect, are expected to have great potential in future clinical applications.

A Compositive Strategy to Study the Pharmacokinetics of TCMs: Taking Coptidis Rhizoma, and Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma as Examples.

Pharmacokinetic studies are crucial for elucidating the effective constituents and formula compatibility of traditional Chinese medicines (TCMs). However, studies have usually been limited to single dosages and detection of systemic blood concentrations. To obtain comprehensive pharmacokinetic information, here we propose a multi-dosage and multi-sampling (blood from portal vein or systemic circulation, and liver) strategy to comparatively study the pharmacokinetics of multi-form TCMs, i.e., pure constituents, TCMs, or TCM formula extracts. Based on this strategy, we studied the pharmacokinetics of pure berberine, berberine in CoptidisRhizoma (CRE), and berberine in CoptidisRhizoma-GlycyrrhizaeRadix etRhizoma extracts (CR-GRE). After simple calculation and comparison of the obtained area under the curve (AUC) values, the results revealed the drastically different pharmacokinetic properties of pure berberine compared to CRE and CR-GRE. The results contribute to explaining the pharmacological loss of berberine activity after purification and the compatibility of the CR-GR drug pair. The results also innovatively showed that it was intestinal absorption that differentiated the pharmacokinetics of CRE and pure berberine, and CRE and CR-GRE. In conclusion, we propose a composite strategy to comparatively study the pharmacokinetics of TCMs, which could provide sufficient information to obtain a comprehensive view, before follow-up mechanism-of-action studies.

Photothermal-Activatable Fe3O4 Superparticle Nanodrug Carriers with PD-L1 Immune Checkpoint Blockade for Anti-metastatic Cancer Immunotherapy.

Checkpoint blockade immunotherapy has shown great potential in clinical cancer therapy, but the body's systemic immune must be fully activated and generates a positive tumor-specific immune cell response. In this work, we demonstrate the design of the immune-adjuvant nanodrug carriers on the basis of poly(ethylene glycol)- block-poly(lactic- co-glycolic acid) copolymer-encapsulated Fe3O4 superparticles (SPs), in which imiquimod (R837), a kind of Toll-like receptor 7 agonist, is loaded. The nanodrug carriers are defined as Fe3O4-R837 SPs. The multitasking Fe3O4-R837 SPs can destroy the 4T1 breast tumor by photothermal therapy (PTT) under near-infrared laser irradiation to generate the tumor-associated antigens because of the high efficiency of tumor magnetic attraction ability and photothermal effect. The PTT also triggers the release of R837 as the adjuvant to trigger a strong antitumor immune response. By further combining with the checkpoint blockade adjusted by programmed death ligand 1 (PD-L1) antibody, the Fe3O4-R837 SP-involved PTT cannot only eliminate the primary tumors but also prevent tumor metastasis to lungs/liver. Meanwhile, this synergistic therapy also shows abscopal effects by completely inhibiting the growth of untreated distant tumors through effectively triggering the tumors infiltrated by CD45+ leukocytes. Such findings suggest that Fe3O4-R837 SP-involved PTT can significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.