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Persistent inflammation in damaged joints results in metabolic dysregulation of the synovial microenvironment, causing pathogenic alteration of cell activity in rheumatoid arthritis (RA). Recently, the role of metabolite and metabolite-sensing G protein-coupled receptors (GPCRs) in the RA-related inflammatory immune response (IIR) has become a focus of research attention. These GPCRs participate in the progression of RA by modulating immune cell activation, migration, and inflammatory responses. Here, we discuss recent evidence implicating metabolic dysregulation in RA pathogenesis, focusing on the connection between RA-related IIR and GPCR signals originating from the synovial joint and gut. Furthermore, we discuss future directions for targeting metabolite-sensing GPCRs for therapeutic benefit, emphasizing the importance of identifying endogenous ligands and investigating the various transduction mechanisms involved., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Geological hazards, especially landslides and mudslides, are frequent in Caoke County, Sichuan Province, China. In September 2022, the mechanical parameters of the soil were obtained through a basic investigation of the landslide characteristics of Ni changgou. Upon that, the finite element-discrete element method was used to reconstruct the three-dimensional numerical model of the landslide on the right bank of Ni changgou, and the initiation mechanism of rainfall on landslide and the formation of debris flow impact dam process were simulated. Furthermore, the pore pressure, stability coefficient as well as displacement of the landslide body were analyzed. It turned out that with the increase of rainfall intensity, the pore water pressure value also increases, where pore water pressure rises rapidly. the slope is close to the unstable edge, Eventually, it tends to one under rainfall conditions, and due to gravity, the slide of the landslide is induced. The duration of landslide movement is about 200 s, the maximum average velocity of the landslide reaches 4.85 m/s, and the average movement distance is close to 500 m. In addition, this method is applied to the Chutougou debris flow, and the corresponding hazard analysis is added which could better show the treatment and application of debris flow in actual engineering., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2 f/f Lyz2 -Cre +/- mice. Synovial inflammation and M1 polarization were improved in GRK2 f/f Lyz2 -Cre +/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPAR γ ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPAR γ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPAR γ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1 + macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Introduction: The adverse effects of high glucose on embryos can be traced to the preimplantation stage. This study aimed to observe the effect of high glucose on early-stage embryos., Methods and Results: Seven-week-old ICR female mice were superovulated and mated, and the zygotes were collected. The zygotes were randomly cultured in 5 different glucose concentrations (control, 20mM, 40mM, 60mM and 80mM glucose). The cleavage rate, blastocyst rate and total cell number of blastocyst were used to assess the embryo quality. 40 mM glucose was selected to model high glucose levels in this study. 40mM glucose arrested early embryonic development, and the blastocyst rate and total cell number of the blastocyst decreased significantly as glucose concentration was increased. The reduction in the total cell number of blastocysts in the high glucose group was attributed to decreased proliferation and increased cell apoptosis, which is associated with the diminished expression of GLUTs (GLUT1, GLUT2, GLUT3). Furthermore, the metabolic characterization of blastocyst culture was observed in the high-glucose environment., Discussion: The balance of glycolysis and oxidative phosphorylation at the blastocyst stage was disrupted. And embryo development arrest due to high glucose is associated with changes in glycolysis and oxidative phosphorylation, as well as abnormalities in the TCA cycle and amino acid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Tong, Wang, Lv, He, Yang, Wang, Xu, Liang, Feng, Niu, Niu and Lu.)

Recent studies have found that blood volume pulse (BVP) in facial videos contains features highly correlated to blood pressure (BP). However, the mapping from BVP features to BP varies from person to person. To address this issue, VidBP has been proposed as a BP detector that can be calibrated based on an individual's data. VidBP is pre-trained on a large dataset to extract BP-related features from BVP. Then, BVP samples and BP labels of an individual are fed into the pre-trained VidBP to create a personal dictionary of BP-related features. When estimating the individual's BP, the current BP-related feature is compared to the features saved in the dictionary, and the BP labels of the similar features are considered as the BP estimate. The performance of VidBP was evaluated on 640 samples of 16 subjects, and it demonstrated significantly lower errors in BP estimation compared to state-of-the-art methods. The personalized calibration of VidBP is a significant advantage, enabling it to better capture the unique mapping from BVP features to BP for each individual.Clinical relevance This study reports a feasible method to estimate BP from facial videos, providing a convenient and cost-effective way for home BP monitoring.

Video-based Photoplethysmography (VPPG) can identify arrhythmic pulses during atrial fibrillation (AF) from facial videos, providing a convenient and cost-effective way to screen for occult AF. However, facial motions in videos always distort VPPG pulse signals and thus lead to the false detection of AF. Photoplethysmography (PPG) pulse signals offer a possible solution to this problem due to the high quality and resemblance to VPPG pulse signals. Given this, a pulse feature disentanglement network (PFDNet) is proposed to discover the common features of VPPG and PPG pulse signals for AF detection. Taking a VPPG pulse signal and a synchronous PPG pulse signal as inputs, PFDNet is pre-trained to extract the motion-robust features that the two signals share. The pre-trained feature extractor of the VPPG pulse signal is then connected to an AF classifier, forming a VPPG-driven AF detector after joint fine-tuning. PFDNet has been tested on 1440 facial videos of 240 subjects (50% AF absence and 50% AF presence). It achieves a Cohen's Kappa value of 0.875 (95% confidence interval: 0.840-0.910, P<0.001) on the video samples with typical facial motions, which is 6.8% higher than that of the state-of-the-art method. PFDNet shows significant robustness to motion interference in the video-based AF detection task, promoting the development of opportunistic screening for AF in the community.

It has been proven that intra-articular injection of mesenchymal stromal cells (MSCs) can alleviate cartilage damage in osteoarthritis (OA) by differentiating into chondrocytes and protecting inherent cartilage. However, the mechanism by which the OA articular microenvironment affects MSCs' therapeutic efficiency is yet to be fully elucidated. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in various cellular processes, such as osteogenesis and immune regulation. Tryptophan (Trp) metabolites, most of which are endogenous ligand for AHR, are abnormally increased in synovial fluid (SF) of OA and rheumatoid arthritis (RA) patients. In this study, the effects of kynurenine (KYN), one of the most important metabolites of Trp, were evaluated on the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). hUC-MSCs were cultured in conditioned medium containing different proportions of OA/RA SF, or stimulated with KYN directly, and then, AHR activation, proliferation, and chondrogenesis of hUC-MSCs were measured. Moreover, the chondroprotective efficiency of short hairpin-AHR-UC-MSC (shAHR-UC-MSC) was determined in a rat surgical OA model (right hind joint). OA SF could activate AHR signaling in hUC-MSCs in a concentration-dependent manner and inhibit the chondrogenic differentiation and proliferation ability of hUC-MSCs. Similar results were observed in hUC-MSCs stimulated with KYN in vitro. Notably, shAHR-UC-MSC exhibited superior therapeutic efficiency in OA rat upon intra-articular injection. Taken together, this study indicates that OA articular microenvironment is not conducive to the therapeutic effect of hUC-MSCs, which is related to the activation of the AHR pathway by tryptophan metabolites, and thus impairs the chondrogenic and chondroprotective effects of hUC-MSCs. AHR might be a promising modification target for further improving the therapeutic efficacy of hUC-MSCs on treatment of cartilage-related diseases such as OA., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Objective . Daily blood pressure (BP) monitoring is essential since BP levels can reflect the functions of heart pumping and vasoconstriction. Although various neural network-based BP estimate approaches have been proposed, they have certain practical shortcomings, such as low estimation accuracy and poor model generalization. Based on the strategy of pre-training and partial fine-tuning, this work proposes a non-invasive method for BP estimation using the photoplethysmography (PPG) signal. Approach . To learn the PPG-BP relationship, the deep convolutional bidirectional recurrent neural network (DC-Bi-RNN) was pre-trained with data from the public medical information mark for intensive care (MIMIC III) database. A tiny quantity of data from the target subject was used to fine-tune the specific layers of the pre-trained model to learn more individual-specific information to achieve highly accurate BP estimation. Main results. The mean absolute error and the Pearson correlation coefficient ( r ) of the proposed algorithm are 3.21 mmHg and 0.919 for systolic BP, and 1.80 mmHg and 0.898 for diastolic BP (DBP). The experimental results show that our method outperforms other methods and meets the requirements of the Association for the Advancement of Medical Instrumentation standard, and received an A grade according to the British Hypertension Society standard. Significance. The proposed method applies the strategy of pre-training and partial fine-tuning to BP estimation and verifies its effectiveness in improving the accuracy of non-invasive BP estimation., (© 2022 Institute of Physics and Engineering in Medicine.)

Remote photoplethysmography (RPPG) can detect heart rate from facial videos in a non-contact way. However, head movement often affects its performance in the real world. In this paper, a novel anti-motion interference method named T-SNE-based signal separation (TSS) is proposed to solve this problem. TSS first decomposes the observed color traces into pulse-related vectors and noise vectors using the T-SNE algorithm. Then, it selects the vector with the most significant spectral peak as the pulse signal for heart rate measurement. The proposed method is tested on a self-collected dataset (17 males and 8 females) and two public datasets (UBFC-RPPG and VIPL-HR). Experimental results show that the proposed method outperforms state-of-the-art methods, especially on the videos containing head movements, improving the Pearson correlation coefficient by 5% compared with the best contrasting method. To summarize, this work significantly strengthens the motion robustness of RPPG, which makes a substantial contribution to the development of video-based heart rate detection., Competing Interests: The authors declare that there are no conflicts of interest related to this article, (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Atrial fibrillation (AF) is the most common arrhythmia, but an estimated 30% of patients with AF are unaware of their conditions. The purpose of this work is to design a model for AF screening from facial videos, with a focus on addressing typical motion disturbances in our real life, such as head movements and expression changes. This model detects a pulse signal from the skin color changes in a facial video by a convolution neural network, incorporating a phase-driven attention mechanism to suppress motion signals in the space domain. It then encodes the pulse signal into discriminative features for AF classification by a coding neural network, using a de-noise coding strategy to improve the robustness of the features to motion signals in the time domain. The proposed model was tested on a dataset containing 1200 samples of 100 AF patients and 100 non-AF subjects. Experimental results demonstrated that VidAF had significant robustness to facial motions, predicting clean pulse signals with the mean absolute error of inter-pulse intervals less than 100 milliseconds. Besides, the model achieved promising performance in AF identification, showing an accuracy of more than 90% in multiple challenging scenarios. VidAF provides a more convenient and cost-effective approach for opportunistic AF screening in the community.

During the SARS period in 2003 and COVID-19 pandemic period in 2020, unexpected severe particulate matter pollution occurred in northern China, although the anthropogenic activities and associated emissions have assumed to be reduced dramatically. This anomalistic increase in PM 2.5 pollution raises a question about how source emissions impact the air quality during these pandemic periods. In this study, we investigated the stable Cu and Si isotopic compositions and typical source-specific fingerprints of PM 2.5 and its sources. We show that the primary PM 2.5 emissions (PM 2.5 emitted directly from sources) actually had no reduction but redistribution during these pandemic periods, rather than the previous thought of being greatly reduced. This finding provided critical evidence to interpret the anomalistic PM 2.5 increase during the pandemic periods in north China. Our results also suggested that both the energy structure adjustment and stringent regulations on primary emissions should be synergistically implemented in a regional scale for clean air actions in China.

Tryptophan 2,3-dioxygenase (TDO2) was an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. We undertook this study to determine a comprehensive analysis of TDO2 expression in immune cells and assess the characterization of immune cell phenotype in TDO2 knockout mice. The expression of TDO2 in various tissues of DBA/1 mice was detected by quantitative real-time PCR (qPCR) and immunohistochemistry. Both flow cytometry and immunofluorescence were used to analyze the expression of TDO2 in immune cells. Furthermore, TDO2 knockout (KO) mice were generated by CRISPR/Cas9 technology to detect immune cell phenotype. TDO2 protein level in liver was tested by western blot. High-performance liquid chromatography was used to detect the level of Trp and Kyn. Flow cytometry was used to test the proportions of splenic lymphocyte subsets in wild-type (WT) and TDO2 KO mice. We found that TDO2 was expressed in various tissues and immune cells, and TDO2 staining was mainly observed in the cytoplasm of cells. There was no difference in the development of immune cells between TDO2 KO mice and WT mice, including T cells, B cells, memory B cells, plasma cells, dendritic cells, and natural killer cells. Interestingly, the reduced M1/M2 ratio was observed in the peritoneal macrophages of TDO2 KO mice. Taken together, these findings enriched the known expression profile of TDO2, especially its expression in immune cells. Our study suggested that TDO2-mediated Trp-Kyn metabolism pathway might be involved in the immune response., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Tumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their "homing" and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions., Methods: Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence., Results: sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α., Conclusion: sTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis., (© 2021. The Author(s).)

Stable isotopic analysis is an important branch of analytical chemistry. Accurate determination of the stable isotopic compositions of substances is critical for tracing their sources and investigating their transformation processes. The new generation of mass spectrometry technology has greatly facilitated the development of high-precision stable isotopic analysis methods. In particular, multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) has emerged as a powerful tool for isotopic composition determination. However, isotopic analysis by MC-ICP-MS is highly sensitive to the sample matrix, which may compromise the precision and accuracy of the analysis. Therefore, it is particularly important to reduce the sample matrix effect using efficient sample purification techniques. This article summarizes the recent progress in sample purification and instrument hyphenation methods for MC-ICP-MS, and provides perspectives on the future application of MC-ICP-MS in different fields.

Ambient particulate matter pollution is one of the leading causes of global disease burden. Epidemiological studies have revealed the connections between particulate exposure and cardiovascular and respiratory diseases. However, until now, the real species of ambient ultrafine particles (UFPs) in humans are still scarcely known. Here we report the discovery and characterization of exogenous nanoparticles (NPs) in human serum and pleural effusion (PE) samples collected from non-occupational subjects in a typical polluted region. We show the wide presence of NPs in human serum and PE samples with extreme diversity in chemical species, concentration, and morphology. Through chemical multi-fingerprinting (including elemental fingerprints, high-resolution structural fingerprints, and stable iron isotopic fingerprints) of NPs, we identify the sources of the NPs to be abiogenic, particularly, combustion-derived particulate emission. Our results provide evidence for the translocation of ambient UFPs into the human circulatory system, and also provide information for understanding their systemic health effects.

Objective: CP-25 attenuates arthritis progression in animal models by inhibiting G protein-coupled receptor kinase 2 (GRK2) membrane expression. This study compared groups treated with high-dose methotrexate (MTX)/leflunomide (LEF) and CP-25 combined with low-dose MTX/LEF in an adjuvant-induced arthritis (AA) rat model and investigated possible mechanisms., Methods: AA was induced in rats via complete Freund's adjuvant. Experimental groups were divided into a normal group; vehicle group; monotherapy groups, including CP-25 (50 mg/kg), MTX (0.25, 0.5 mg/kg), and LEF (5, 10 mg/kg); and CP-25 (50 mg/kg)-combined MTX (0.25 mg/kg)/LEF (5 mg/kg) groups. We measured cytokine levels, phosphorylation and protein expression, and interactions between proteins. The role of GRK2 on phosphorylated extracellular signal-regulated kinase (p-ERK) was determined via GRK2-siRNA using a high content imaging system., Results: Therapeutic effects, including pathology and cytokine balance, were equivalent between the CP-25-combination groups and the high-dose MTX/LEF groups. P38, ERK, and c-Jun N-terminal kinase (JNK) activation in AA fibroblast-like synoviocytes (FLS) was reduced in the treatment groups; GRK2 expression was only inhibited in the CP-25 group. Interactions between GRK2 and p-ERK decreased in the vehicle group and were restored in the CP-25 group. GRK2 membrane expression and p-ERK nuclear expression increased in FLS pre-treated with tumour necrosis factor alpha and stimulated with prostaglandin E2. Nuclear expression of p-ERK increased in GRK2-siRNA FLS., Conclusion: Equivalent therapeutic effects were observed between CP-25-combination groups and high-dose MTX/LEF groups. CP-25 inhibited p-ERK by reducing the membrane expression of GRK2 in FLS from AA rats., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Stability of silver sulfide nanoparticle (Ag 2 S-NP) in the environment has recently drawn considerable attention since it is associated with environmental risk. Although the overestimated stability of Ag 2 S-NP in aqueous solution has already been recognized, studies on transformation of Ag 2 S-NP in environmental water are still very scarce. Here we reported that Ag 2 S-NP could undergo dissolution by manganese(IV) oxide (MnO 2 ), an important naturally occurring oxidant in the environment, even in environmental water, although the dissolved silver would probably be adsorbed onto the particles (>0.45 μm) in environmental water, mitigating the measurable levels of dissolved silver. The extent and rate of Ag 2 S-NP dissolution rose with the increasing concentration of MnO 2 . In addition, environmental factors including natural organic matter, inorganic salts and organic acids could accelerate the Ag 2 S-NP dissolution by MnO 2 , wherein an increase in dissolution extent was also observed. We further documented that Ag 2 S-NP dissolution by MnO 2 was highly dependent on O 2 and it was an oxidative dissolution, with the production of SO 4 2- . Finally, dissolution of Ag 2 S-NP by MnO 2 affected zebra fish (Danio rerio) embryo viability, showing significant reduction in embryo survival and hatching rates, compared to embryos exposed to Ag 2 S-NP, MnO 2 or dissolved manganese alone. These findings would further shed light on the stability of Ag 2 S-NP in the natural environment - essential for comprehensive nano risk assessment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Kushen (Radix Sophorae Flavescentis) is the dried roots of Sophora Flavescens Ait, alkaloids and flavonoids are the main active constituents of Radix Sophorae Flavescentis. The influence of Radix Sophorae Flavescentis on the activities of CYP450 isoforms CYP2B6, CYP2C19, CYP1A2, CYP2C9, CYP3A4 and CYP2D6 were evaluated by cocktail method. The rats were randomly divided into Radix Sophorae Flavescentis group and control group. The Radix Sophorae Flavescentis group rats were given 5 g/kg Radix Sophorae Flavescentis decoction by intragastric administration. The six probe drugs (bupropion, omeprazole, phenacetin, tolbutamide, midazolam and metroprolol) were given to rats through intragastric administration, and the plasma concentration were determined by UPLC-MS/MS. The result of Radix Sophorae Flavescentis group compared to control group, there were statistical pharmacokinetics difference for omeprazole, phenacetin, tolbutamide and metroprolol. It indicated that the Radix Sophorae Flavescentis may induce the activities of CYP2D6, and inhibit of CYP2C19, CYP1A2 and CYP2C9 of rats. As other drugs are always used after Radix Sophorae Flavescentis, interactions between other drugs and Radix Sophorae Flavescentis undertake the risk of either diminished efficacy or adverse effects. This may give advising for reasonable drug use after Radix Sophorae Flavescentis.

Magnoflorine is one of the most widespread aporphine alkaloids. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of magnoflorine in rat plasma and mouse tissue have been developed and validated. After addition of nuciferine as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used for samples treatment. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 342.8→298.2 for magnoflorine and m/z 296.0→265.1 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for magnoflorine in rat plasma and tissue. Mean recoveries of magnoflorine in rat plasma were better than 83.0%. RSD of intra-day and inter-day precision were both less than 9%. The accuracy of the method was between 95.5% and 107.5%. The method was successfully applied to pharmacokinetics and tissue distribution study of magnoflorine. The absolute bioavailability of magnoflorine was reported as 22.6%. The magnoflorine underwent a rapid and wide distribution to tissues; the level of magnoflorine in liver is highest, then followed by heart, spleen and lung. Based on tissue distribution data, a back-propagation artificial neural network (BP-ANN) method was developed and it could be used to predict the concentrations of magnoflorine in tissues.

MGCD0103, an isotype-selective HDACi, has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In this study, we developed a serum metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of intragastric administration of MGCD0103 on rats. The MGCD0103 group rats were given 20, 40, 80 mg/kg of MGCD0103 by intragastric administration each day for 7 days. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) revealed that intragastric administration of MGCD0103 induced metabolic perturbations. As compared to the control group, the levels of L-alanine, L-isoleucine, and L-leucine of MGCD0103 group decreased. The results indicate that metabolomic methods based on GC-MS may be useful to elucidate side effect of MGCD0103 through the exploration of biomarkers (L-alanine, L-isoleucine, and L-leucine). According to the pathological changes of liver at difference dosage, MGCD0103 is hepatotoxic and its toxity is dose-dependent.

Background: Depression is among the most common neuropsychiatric complications after stroke, having a negative impact on one's quality of life. A number of therapeutic modalities have been used for post-stroke depression (PSD) including traditional Chinese medicine (TCM). However, a lack of objectivity in TCM hampers further improvement in diagnosis and research, since TCM diagnosis is mainly based on subjective judgment of clinicians. In this study, a modern TCM diagnostic device was used to conduct an objective study of pulse and tongue features in PSD patients and healthy individuals., Methods: A total of 67 volunteers participated. Pulse and tongue information of each participant was acquired and analyzed by the TCM Four Diagnosis Auxiliary Apparatus. Quantitative data were gathered and compared between the PSD group and the healthy group., Results: Higher rates of weak, slow, slippery, and string pulse were observed in the PSD group (p < 0.01), whereas normal pulse (p < 0.01) was detected in the healthy group. In the tongue analysis, higher rates of purple tongue (p < 0.01) with yellow fur (p < 0.01) and pale-pink tongue (p = 0.023) with white fur (p < 0.01) were observed in the PSD and the healthy groups, respectively. Abnormal tongue features (old, soft, thin, enlarged, thorny, and cracked) were detected (p < 0.05) in the PSD group., Conclusions: Objective and quantitative data of PSD patients and healthy individuals may help providing valuable clinical information for PSD research and establish quantitative TCM diagnostic standards for pulse and tongue diagnosis in clinical practice and research., (© 2015 S. Karger GmbH, Freiburg.)

Traditional Chinese medicine (TCM) pulse diagnosis can reflect the condition of human bodies. 44 young healthy human beings were involved in the investigation of the relationship between the three dimensional motion of the radial artery and the spatiality, rhythmicity, formability and intensity of TCM pulse diagnosis in TCM pulse diagnostics. The color Doppler vascular imaging, the self-designed cardioelectric phasic marking and non-pressure arm bath-tube were used in the study. Both the radial artery and other arm superficial arteries had three forms of motion, namely diametrical motion, axial motion and the displacement of the axial center. The three forms of motion changed periodically, which was identical with that found in pulsation. The displacement of the vascular axial center was a three-dimensional message of the overall vascular revolving motion observed on a two-e level. Systematically studying the rules of vascular motion and the relationship between the rules of vascular motion and the spatiality, rhythmicity, formability and intensity of TCM pulse patterns has great significance in revealing the specificity of the vascular motion and explaining the mechanisms in the formation of TCM pulse diagnosis. This research could make TCM pulse diagnosis more understandable.