[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Research on the Application of Molecular Image Processing in Rice Quality Inspection.

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

Chemical proteomics unveils that seventy flavors pearl pill ameliorates ischemic stroke by regulating oxidative phosphorylation.

Ischemic stroke has high mortality and morbidity rates and is the second leading cause of death in the world, but there is no definitive medicine. Seventy Flavors Pearl Pill (SFPP) is a classic formula in Tibetan Medicine. Clinical practice has shown the attenuation effect of SFPP on blood pressure disorders, strokes and their sequelae and other neurological symptoms, but its mechanism remains to be elucidated. In this study, we established three animal models in vivo and three cell models to evaluate the anti-hypoxia, anti-ischemia, and reperfusion injury prevention effects of SFPP. Quantitative proteomics revealed that oxidative phosphorylation (OXPHOS) is essential for SFPP's efficacy. Then, cysteine-activity based protein profiling technology, which reflects redox stress at the proteome level, was employed to illustrate that SFPP brought functional differences of critical proteins in OXPHOS. In addition, quantitative metabolomics revealed that SFPP affects whole energy metabolism with OXPHOS as the core. Finally, we performed a compositional identification of SFPP to initially explore the components of potential interventions in OXPHOS. These results provide new perspectives and tools to explore the mechanism of herbal medicine. The study suggests that OXPHOS could be a potential target for further research and intervention of ischemic stroke treatment.

Effect of calcium plus Vitamin-D combined with calcitriol in the treatment of patients with Type-2 diabetes and osteoporosis: A retrospective observational analysis.

Objective: To explore the clinical effect of calcium plus Vitamin-D combined with calcitriol in the treatment of patients with type-2 diabetes mellitus (T2DM) patients and osteoporosis. Methods: In this retrospective observational study clinical records of 90 patients with T2DM combined with osteoporosis, treated in The Quzhou Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were incuded. All patients received basic hypoglycemic treatment. Of 90 patients, 43 received calcium plus Vitamin-D adjuvant therapy (Control-group), and 47 patients received calcium plus Vitamin-D combined with calcitriol adjuvant therapy (Observation-group). Clinical efficacy, adverse reactions, bone metabolism levels, and changes in bone density levels were compared between the two groups. Results: The clinical efficacy of the treatment was significantly higher in the Observation-group (93.6%) compared to the Control-group (83.7%; p<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (p>0.05). After treatment, bone metabolism and bone density indicators in both groups improved, and were significantly better in the Observation-group compared to the Control-group (p<0.05). Conclusions: Combination of calcium plus Vitamin-D and calcitriol adjuvant therapy in patients with T2DM and osteoporosis is safe and associated with better treatment efficacy, improved bone metabolism and bone density parameters than calcium plus Vitamin-D treatment alone.

Effect and pharmacological mechanism of Salvia miltiorrhiza and its characteristic extracts on diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a severe diabetic microvascular complication with an increasing prevalence rate and lack of effective treatment. Traditional Chinese medicine has been proven to have favorable efficacy on DN, especially Salvia miltiorrhiza Bunge (SM), one of the most critical and conventional herbs in the treatment. Over the past decades, studies have demonstrated that SM is a potential treatment for DN, and the exploration of the underlying mechanism has also received much attention. AIM OF THIS REVIEW: This review aims to systematically study the efficacy and pharmacological mechanism of SM in the treatment of DN to understand its therapeutic potential more comprehensively. MATERIALS AND METHODS: Relevant information was sourced from Google Scholar, PubMed, Web of Science, and CNKI databases. RESULTS: Several clinical trials and systematic reviews have indicated that SM has definite benefits on the kidneys of diabetic patients. And many laboratory studies have further revealed that SM and its characteristic extracts, mainly including salvianolic acids and tanshinones, can exhibit pharmacological activity against DN by the regulation of metabolism, renal hemodynamic, oxidative stress, inflammation, fibrosis, autophagy, et cetera, and several involved signaling pathways, thereby preventing various renal cells from abnormal changes in DN, including endothelial cells, podocytes, epithelial cells, and mesangial cells. CONCLUSION: As a potential drug for the treatment of DN, SM has multi-component, multi-target, and multi-pathway pharmacological effects. This work will not only verify the satisfactory curative effect of SM in the treatment of DN but also provide helpful insights for the development of new anti-DN drugs and the application of traditional Chinese medicine.

Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RYZBP) is a traditional Tibetan medicine that has been used for over 300 years in China to treat neurological diseases, specifically neuropathic pain (NP). However, its characteristics and mechanism of action in treating NP remains unclear. AIM OF THE STUDY: Based on animal experiments and transcriptomics to evaluate the characteristics and mechanism of RYZBP in treating NP. METHODS: Mice were divided into six groups using random assignment: sham-operation group, spinal nerve ligation (SNL) group, RYZBP low (0.65 g kg-1), medium (1.30 g kg-1), high (2.60 g kg-1) doses groups, and positive drug pregabalin (PGB, 0.05 g kg-1) group. Mice received intragastrical administered for 14 consecutive days. SNL and intrathecal injection models were employed. The analgesic effects were assessed using the Von Frey test, Acetone test, and Hot Plate test. L5 spinal dorsal horns were collected for transcriptomics on day 15. The potential signaling pathways and Hub genes of RYZBP to ameliorate NP were obtained through transcriptomics and network pharmacology. Molecular docking was utilized to evaluate the binding ability of candidate active ingredients with the Hub genes. Finally, western blot (WB) and immunofluorescence (IF) were used to validate the predicted targets. RESULTS: RYZBP demonstrated a dose-dependent alleviation of mechanical allodynia, cold and heat stimulus-induced pain in SNL mice. Transcriptomics analysis identified 24 differentially expressed genes, and pathway enrichment analysis revealed that the CXCL10-CXCR3 signal axis may be the primary biological pathway through which RYZBP relieve NP. Molecular docking test indicated that the active ingredient in RYZBP exhibit a strong affinity for the target protein CXCL10. WB and IF tests showed that RYZBP can significantly inhibit CXCL10 and CXCR3 and its downstream molecules expression in the spinal dorsal horn of SNL mice. Additionally, intrathecal injection of rmCXCL10 worsened pain hypersensitivity, while RYZBP was able to suppress the pain hypersensitivity response induced by rmCXCL10 and reduce the expression levels of CXCL10 and CXCR3 and its downstream molecules. CONCLUSION: RYZBP had a significant analgesic effect on NP model, and this effect may be related to inhibiting the CXCL10-CXCR3 pathway in the spinal dorsal horn.

The Selective Separation of Carnosic Acid and Rosmarinic Acid by Solid-Phase Extraction and Liquid-Liquid Extraction: A Comparative Study.

Rosmarinus officinalis leaves (ROLs) are widely used in the food and cosmetics industries due to their high antioxidant activity and fascinating flavor properties. Carnosic acid (CA) and rosmarinic acid (RA) are regarded as the characteristic antioxidant components of ROLs, and the selective separation of CA and RA remains a significant challenge. In this work, the feasibility of achieving the selective separation of CA and RA from ROLs by solid-phase extraction (SPE) and liquid-liquid extraction (LLE) was studied and compared. The experiments suggested that SPE with CAD-40 macroporous resin as the adsorbent was a good choice for selectively isolating CA from the extracts of ROLs and could produce raw CA with purity levels as high as 76.5%. The LLE with ethyl acetate (EA) as the extraction solvent was more suitable for extracting RA from the diluted extracts of ROLs and could produce raw RA with a purity level of 56.3%. Compared with the reported column chromatography and LLE techniques, the developed SPE-LLE method not only exhibited higher extraction efficiency for CA and RA, but can also produce CA and RA with higher purity.

Polyphyllin VI screened from Chonglou by cell membrane immobilized chromatography relieves inflammatory pain by inhibiting inflammation and normalizing the expression of P2X3 purinoceptor.

Objective: Inflammatory pain is one of the most common diseases in daily life and clinic. In this work, we analysed bioactive components of the traditional Chinese medicine Chonglou and studied mechanisms of their analgesic effects. Material and methods: Molecular docking technology and U373 cells overexpressing P2X3 receptors combined with the cell membrane immobilized chromatography were used to screen possible CL bioactive molecules interacting with the P2X3 receptor. Moreover, we investigated the analgesic and anti-inflammatory effects of Polyphyllin VI (PPIV), in mice with chronic neuroinflammatory pain induced by CFA (complete Freund's adjuvant). Results: The results of cell membrane immobilized chromatography and molecular docking showed that PPVI was one of the effective compounds of Chonglou. In mice with CFA-induced chronic neuroinflammatory pain, PPVI decreased the thermal paw withdrawal latency and mechanical paw withdrawal threshold and diminished foot edema. Additionally, in mice with CFA-induced chronic neuroinflammatory pain, PPIV reduced the expression of the pro-inflammatory factors IL-1, IL-6, TNF-α, and downregulated the expression of P2X3 receptors in the dorsal root ganglion and spinal cord. Conclusion: Our work identifies PPVI as a potential analgesic component in the Chonglou extract. We demonstrated that PPVI reduces pain by inhibiting inflammation and normalizing P2X3 receptor expression in the dorsal root ganglion and spinal cord.

Construction and application of a prediction model for the delivery outcome of women with scarred uterus based on ultrasonic parameters.

OBJECTIVE: To explore the application value of the prediction model for delivery outcome of women with scarred uterus based on ultrasonic parameters. METHODS: In this retrospective study, a total of 100 pregnant women with scarred uterus who delivered in Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine were selected as the research subjects. Adverse pregnancy outcomes included premature delivery, low birth weight, neonatal asphyxia, postpartum hemorrhage, and uterine rupture. In line with delivery outcome, the pregnant women were segmented into good outcome group (n = 78) and poor outcome group (n = 22). We collected and compared the clinical data and the ultrasonic parameters of pregnant women of the two groups. Multivariate logistic regression analysis was conducted to explore the risk factors affecting the delivery outcome of women with scarred uterus and to establish a prediction model. RESULTS: Multivariate logistic regression analysis showed that low hemoglobin (Hb) before delivery, high grade of uterine scar, low muscle thickness of lower uterine segment, and low blood flow index were the risk factors for poor delivery outcome of women with scarred uterus. According to the risk factors, the prediction model was obtained: Prob = 1/[1 + e^ (-5.110-2.568 * Pre-delivery Hb - 1.697 * uterine scar grade -2.895 * lower uterine muscle thickness + 19.584 * blood flow index)]. The sensitivity, specificity and area under the curve were 90.0, 91.0 and 0.959, respectively. After validation, the sensitivity and specificity were 85.71 and 87.04, respectively. CONCLUSION: Low Hb before delivery, low grade of uterine scar, low musculature thickness of lower uterine segment, and low blood flow index were the risk factors for poor delivery outcome of women with scarred uterus. The establishment of prediction model based on risk factors could effectively evaluate the risk of poor delivery outcome of women with scarred uterus.

A discovery of clinically approved Panlongqi Tablet for repositioning to treat osteoarthritis by inhibiting PI3K/AKT activation.

BACKGROUND: Panlongqi Tablet (PLQT) is a Chinese patent drug composed of 29 kinds of traditional Chinese medicines. Clinical practice has shown that PLQT can relieve osteoarthritis-caused joint pain, but its effects and mechanisms in other pathological links of osteoarthritis have not been characterized. PURPOSE: The purpose of this study is to reposition the pharmacodynamic effects of PLQT through network pharmacology analysis combined with experimental validation, and also to preliminarily explore its possible mechanism. METHODS: On the basis of integrating the relevant targets of PLQT in multiple drug databases and osteoarthritis-related targets in the disease database, an interaction network of related genes was constructed. The hub candidate targets of PLQT in the treatment of osteoarthritis were determined by calculating the main network topological characteristics, The specific functions and pathways of these targets acting on osteoarthritis were modularly analyzed. In addition, the modified Hulth-induced rat model of osteoarthritis and IL-1ß-induced in vitro model of osteoarthritis were established to further validate the potential efficacy and possible mechanism of PLQT. RESULTS: A total of 138 key targets related to osteoarthritis were selected based on topological parameters, and their biological functions were mainly enriched in four over-expressed modules of cartilage degeneration, inflammatory response, immune response, and subchondral bone metabolism. The hub candidate targets had the highest enrichment degree in the TLR4-RAC1-PIK3CA-Akt-NFκB signaling axis of the PI3K/Akt signaling pathway. In vivo results showed that PLQT treatment significantly inhibited the degeneration of proteoglycan and collagen in the cartilage of osteoarthritis rats, suppressed chondrocyte apoptosis, and reduced the Mankin score of joints. Moreover, PLQT alleviated synovial inflammation, reduced the Krenn score of synovium, inhibited the formation of osteophytes in osteoarthritis rats, reduced the bone mineral density (BMD), fractional bone volume (BV/TV), and trabecular thickness (Tb.Th.), as well as increased the trabecular separation (Tb.Sp.) of subchondral bone and the thickness of the subchondral bone plate (SBP.Th.). PLQT suppressed the expressions of TLR4, RAC1, PIK3CA, p-Akt, MMP-13, and ADAMTS-5 in the cartilage, and inhibited the expression of NFκB p65 in the chondrogenic nucleus. Meanwhile, as downstream effector factors of the predictive pathways, the levels of serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) were decreased after PLQT treatment. In vitro results also showed that PLQT could inhibit the expression of key proteins and downstream effector factors of the signaling axis, and this inhibition disappeared when pathway agonists were added. CONCLUSION: PLQT exerted pharmacological effects on the key pathological links of osteoarthritis including chondrocyte apoptosis, extracellular matrix degradation, inflammation, and subchondral bone metabolism by inhibiting the TLR4-RAC1-PIK3CA-Akt-NFκB axis-related proteins.

Integrated approach toward absorption, distribution, metabolism, and excretion of Xiaoke pills in zebrafish based on UPLC-HRMS and DESI-MS techniques.

Traditional Chinese medicine (TCM) has been used in clinical settings for over 2000 years in China. The study of the absorption, distribution, metabolism, and excretion (ADME) of TCM in vivo could be beneficial for the discovery of the active components in TCM. However, the conventional strategies used for ADME research are based on rodent models and have the characteristics of lengthy experimental periods, complex processes, and extensive data processing, which make it difficult to perform rapid analyses and high-throughput ADME screening of the medicinal components of TCM. In this study, an integrated high-throughput research strategy for the in vivo ADME analysis of TCM was established based on a zebrafish model. Accordingly, a combination of ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, and in-house non-targeted precise-and-thorough background-subtraction (PATBS) data post-processing techniques were successfully applied for the analysis of the metabolism of zebrafish exposed to Xiaoke pills. A total of 49 compounds related to Xiaoke pills (including 13 prototypical components and 36 metabolites) were detected in zebrafish. In total, 32 of them, including puerarin, daidzein, deoxyschizandrin, formononetin, and glibenclamide, which have been identified to have hypoglycemic activity in our previous studies and are phase I and phase II metabolites resulting from the hydroxylation, demethylation, glucuronidation, sulfation, and glycosylation of the prototypical components in vivo, were found in rats treated with Xiaoke pills. Furthermore, the overall distribution of the known compounds in zebrafish exposed to Xiaoke pills was explored using DESI-MS. In summary, this study provides a practical approach for the high-throughput screening of the active components of TCM using a zebrafish model.

Exploration of Q-Marker of Rhubarb Based on Intelligent Data Processing Techniques and the AUC Pooled Method.

Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb's therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The in vivo experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1ß] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.

The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord.

ETHNOPHARMACOLOGICAL RELEVANCE: Until now, inflammatory pain, especially ones with central sensitization in the spinal cord, is far from effectively treated. Yu-Xue-Bi Tablets (YXB) is a patented medicine, which has been widely applied for inflammatory pain. However, its therapeutic characteristics and mechanism remain unknown. AIM OF THE STUDY: This study is designed to evaluate the analgesic characteristics and explore the underlying mechanism of YXB in the inflammatory pain model induced by Complete Freund's Adjuvant (CFA). MATERIALS AND METHODS: The analgesic effects were measured by Von Frey test. The expression of calcitonin gene-related peptide (CGRP) was quantified by immunofluorescence. The expression of immune factors was analyzed via Luminex assay. The further quantifications of C-C Motif chemokine ligand 3 (CCL3) were verified by Enzyme-linked immunosorbent assay (ELISA). The transmigration of macrophage and activation of microglia were evaluated by immunofluorescence. Spinal injections of purified CCL3, CCR1 antagonist (J113863) and CCR5 antagonist (Maraviroc) were used to clarify roles of CCL3 assumed in the pharmacological mechanism of YXB. RESULTS: In CFA mice, YXB ameliorated the mechanical allodynia in dose and time dependent way, suppressed the central sensitization in dose dependent way. In the L5 spinal cord, YXB downregulated the expression of macrophage M1 pro-inflammatory factors TNFRI and CCL3, inhibited the transmigration of circulating macrophage and the activation of microglia. Purified CCL3 led to the transmigration of macrophage, activation of microglia, central sensitization, and mechanical allodynia in the Sham mice. Inhibitors of CCR1 and CCR5 attenuated above symptoms in CFA mice. Purified CCL3 blocked YXB mediated down regulation of CCL3, inhibition of macrophage transmigration, but not activation of microglia. CONCLUSION: YXB exerts the analgesic effects by inhibiting CCL3-mediated peripheral macrophage transmigrate into spinal cord. This study provided a novel approach for inflammatory pain treatment and new insight into the pharmacological action of YXB.

Recent Progress on Mass Spectrum Based Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Traditional Chinese Medicine.

BACKGROUND: The absorption, distribution, metabolism, and excretion (ADME) of traditional Chinese medicine (TCM) components are closely related to their therapeutic efficacy, toxic effects, and drug interactions. Based on the study of the whole process of ADME in TCM, it is important to screen out the key pharmacokinetic index components (pharmacokinetics PK/toxicokinetics TK makers), which can be beneficial for their clinical application or drug development. Although the detection of traditional small molecular drug's in vivo ADME process can be achieved by radioisotope methods, this approach might not be useful for the case of TCM. In detail, it is very difficult to label and trace each component in complex Chinese medicine, while it is also difficult to accurately follow the position of tracer in the whole in vivo process. In short, it is a tough task to obtain the ADME information of Chinese medicine, especially in the case of a clinical study. METHODS: We searched several scientific databases, including Pubmed, ACS, ScienceDirect, Springer, Wiley, etc., by using "Chinese medicine" and "in vivo metabolism" as keywords. By summarizing the current reports as well as our recent progress in this field, this review aims to summarize current research methods and strategies for ADME study of TCM based on high-resolution mass spectrometry-based data acquisition and data mining technology which is an important approach but has not been systematically reviewed. RESULTS: With the development of various hybrid tandem high-resolution mass spectrometry (Q-TOF, LTQ FT, Q-Exactive), liquid chromatography-high resolution mass spectrometry (LC-HRMS) has become the mainstream method in studying ADME process of TCM. This review aims to comprehensively summarize current research technologies and strategies based on high-resolution mass spectrometry, with emphasis on the following three aspects: (1) comprehensive and automatic acquisition technologies for the analysis of in vivo TCM components (i.e., BEDDA); (2) quick and comprehensive identification techniques for analyzing in vivo chemical substances and metabolites of TCM (i.e., PATBS or metabolomic analysis); (3) efficient correlation determination between in vivo or in vitro compounds and their metabolic transformation (i.e., MTSF). CONCLUSION: To the best of our knowledge, this is a pioneering review for systematically summarizing the analysis methods and strategies of ADME in TCM, which can help understand the whole ADME process, therapeutic molecular basis, or toxic substances of TCM. Furthermore, this review can also provide a feasible strategy to screen out PK/TK markers of TCM, while this information can be helpful to elucidate the pharmacodynamics or toxicity mechanisms of Chinese medicines and be useful in their future drug development. At the same time, we also hope that this review can provide ideas for further improvement of TCM analysis methods and help rational clinical use of TCM and the development of new drugs.

HRPIF data mining based on data-dependent/independent acquisition for Rhei Radix et Rhizoma metabolite screening in rats.

In traditional Chinese medicine (TCM), components with identical nuclei often share structural similarity, indicating the possibility of similar second-level mass spectrometry (MS/MS) fragments. High-resolution product-ion filter (HRPIF) technique can be utilized to identify metabolites, with similar fragments, in vivo. In principle, this technique applies to TCM; however, its application has been restricted due to the limitations of traditional MS/MS data acquisition. Therefore, a novel analysis strategy, based on data-dependent acquisition (DDA) and data-independent acquisition (DIA) datasets, has been developed for the determination of template product ions and efficient non-targeted identification of TCM-related components in vivo by HRPIF and background subtraction (BS). This DDA-DIA combination strategy, taking Rhei Radix et Rhizoma as a test case, identified 71 anthraquinone prototype components in vitro (36 of which were discovered for the first time), and 45 related components in vivo, confirming glucuronidation and sulfation as the main reactions. The developed strategy could rapidly identify TCM-related components in vivo with high sensitivity, indicating the immense importance of this novel HRPIF data mining technology in TCM analysis.

Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid.

Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

Mindfulness-based therapy versus cognitive behavioral therapy for people with anxiety symptoms: a systematic review and meta-analysis of random controlled trials.

BACKGROUND: Mindfulness-based interventions (MBIs) and cognitive behavioral therapy (CBT) have both been shown to be effective treatment approaches for anxiety. The purpose of this paper was to directly investigate the ability of MBIs and CBT to improve anxiety symptoms (primary outcome), as well as depression symptoms and sleep quality (second outcome). METHODS: We searched the following electronic databases from 1st December, 2019 to 14th January 2021: English databases including PubMed, PsycINFO, Web of Science, the Cochrane Library, Elsevier, Springer Link, Wiley Online Library, ClinicalTrails, and Embase, and Chinese database including CNKI, WANFANG, and CQVIP. The eligibility criteria included the following: (I) patients with anxiety disorders or symptoms of anxiety; and those with physical or mental disorders with comorbid anxiety symptoms; (II) randomized controlled trial (RCT) design; (III) the treatment group received MBIs; (IV) the control group received CBT; and (V) the treatment outcomes were anxiety, depression, and sleep quality. RESULTS: In total, 4,095 abstracts were reviewed. Of these, the full-texts of 45 articles were read in detail; and 11 RCTs were finally included in the analysis. Upon completion of MBIs and CBT group sessions, the study outcomes (mean anxiety, depression, and sleep quality scores) revealed no difference between MBIs and CBT with regards to anxiety, depression, and sleep quality post-intervention. Subgroup analysis was also performed, and the results indicated that MBIs may provide a small advantage for people with anxiety symptoms compared to CBT [standard mean difference (SMD): -0.36, 95% confidence interval (CI): -0.66 to -0.06], while the CBT group demonstrated a small comparative advantage for anxiety in the Liebowitz Social Anxiety Scale (LSAS) and Social Phobia Inventory (SPIN) scales, as well as mindfulness-based stress reduction (MBSR) in the types of MBIs (LSAS: SMD: 0.35, 95% CI: 0.08 to 0.63; SPIN: SMD: 0.51, 95% CI: 0.11 to 0.92; MBSR: SMD: 0.41, 95% CI: 0.07 to 0.74). DISCUSSION: There was no significant difference between MBIs and CBT in terms of the treatment outcomes of anxiety, depression, and sleep quality. MBIs could be used as an alternative intervention to CBT for anxiety symptoms. TRIAL REGISTRATION: This meta-analysis was conducted in line with the PRISMA guideline and was registered at PROSPERO https://www.crd.york.ac.uk/PROSPERO/ (CRD42021219822).

Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed via the gastrointestinal tract and formed via biotransformation in human, respectively. Together with data from screening by comprehensive 2D angiotensin-converting enzyme 2 (ACE2) biochromatography, 8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation. Results show that rhein, forsythoside A, forsythoside I, neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2. For the first time, this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human. It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.

Effects of rhodioloside on the neurological functions of rats with total cerebral ischemia/reperfusion and cone neuron injury in the hippocampal CA1 region.

Rhodioloside, the main effective constituent of Rhodiola rosea, demonstrates antiaging and antioxidative stress functions and inhibits calcium overloading in cells. These functions imply that rhodioloside may exert protective effects on hippocampal neurons after total cerebral ischemia/reperfusion injury. In this study, male Wistar rat models of total cerebral ischemia were constructed and randomly divided into four groups: sham-operation, ischemia/reperfusion, low-dosage, and high-dosage groups. The result showed that rhodioloside treatment reduced the apoptosis rates of hippocampal neurons and the histological grades of cone cells in the hippocampal CA1 region, but neuronal density was significantly increased. Besides, the protein expressions of Bcl-2/Bax and p53 were measured and found Bcl-2/Bax was increased and p53 protein level was reduced. Therefore, rhodioloside might have protective effects on rats with ischemia/reperfusion brain injury.

Multicenter Clinical Trials Analyzing Efficacy and Safety of Topical Cortex Phellodendri Compound Fluid in Treatment of Diabetic Foot Ulcers.

BACKGROUND The aim of this study was to analyze the clinical application of cortex phellodendri compound fluid (CPCF) in the treatment of diabetic foot ulcers. MATERIAL AND METHODS From January 2012 to December 2015, a total of 720 cases of diabetic foot ulcers (DFU) were randomly assigned into an experimental group (n=540) that was treated by CPCF and a control group (n=180) that was treated by a Kangfuxin solution (KFS). After 4 weeks of treatment, their ulcer area, serum growth factor, clinical total effective rate, and incidence of adverse events were assessed. RESULTS There were 720 patients who completed the trial. The experimental group was superior to the control group in reducing ulcer area, increasing growth factor content, and total effective rate (P<0.05). There was no significant difference in the adverse events rates between the 2 groups. CONCLUSIONS CPCF external treatment of diabetic foot ulcer can promote ulcer healing and increase the concentration of growth factors, and it is safe and reliable.