Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by ^99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with ¹⁸F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with ¹⁸F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and ¹⁸F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and ¹⁸F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.
Male ; Humans ; Middle Aged ; Aged ; Stroke Volume ; Heart Failure ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Reproducibility of Results ; Prospective Studies ; Coronary Artery Bypass ; Ventricular Dysfunction, Left ; Tomography, Emission-Computed, Single-Photon ; Perfusion ; Myocardium

UHPLC-Q-TOF/MS metabonomics technology was used to clarify the metabolic regulation pathways by which Platycodon total saponins (PTS) exert antitussive and expectorant effects in a mouse cough model, in which coughing is induced by concentrated ammonia, and in a phenol red excretion model. After approval by the Experimental Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235), the mice were randomly divided into a normal group, a model group, a positive drug group and a PTS group. Endogenous metabolites in mouse serum were identified by UHPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for multivariate analysis. Metabolic pathways were analyzed by the Metaboanalyst platform. The results show that PTS can significantly prolong the cough latent period and cough frequency of mice, and significantly increase phenol red excretion. UHPLC-Q-TOF/MS identified 19 metabolites related to cough, and PTS significantly decreased 16 of them; 17 metabolites related to expectoration were identified, and PTS decreased the levels of all. Metabolic pathway analysis showed that linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism were the main pathways involved in serum metabolite changes in this mouse cough model. Linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism and α-linolenic acid metabolism were the main pathways involved in serum metabolite changes in the phenol red excretion model. This study is the first to elucidate the regulation of antitussive and expectorant metabolic pathways and the effect of PTS on these pathways.

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
Drug Carriers ; Emodin ; Follow-Up Studies ; Lipids ; Nanostructures

Objective To analyze the sequences of mitochondrial cytochrome C oxidase subunit I gene (COI) and 18S ribosomal RNA gene (18S rRNA), so as to identify the feasible DNA barcodes for 4 species of cheyletid mites and improve the DNA barcoding database for cheyletid mites. Methods Cheyletid mite samples were collected from small-scale flour mills in Fuyang, Wuhu and Tongling cities of Anhui Province from May 2018 to July 2019, extracted and morphologically identified. Then, genomic DNA was extracted from a single cheyletid mite, and the COI and 18S rRNA gene sequences were obtained by PCR amplification, cloning and sequencing. The obtained sequences were aligned using the BLAST software. Multiple sequence alignment was done using the software ClustalX version 1.83 using the known gene sequences from cheyletid mites. The genetic distance was calculated using the software MEGA X, and the phylogenetic tree was created using the maximum likelihood method. Results The DNA barcoding results of Cheyletus malaccensis, C. carnifex and Cheletomorpha lepidopterorum were consistent with the morphological identification, while no sequences pertaining to Eucheyletia reticulate were retrieved in the GenBank database. The proportions of A + T were 69.6% and 55.1% in the COI and 18S rRNA sequences of 4 cheyletid mites species, respectively, and the numbers of base substitutions were 137 and 46, respectively. There were 154 to 321 and 58 to 99 inter-species variation loci in the COI and 18S rRNA gene sequences of 4 cheyletid mites species, respectively, and the intra-species genetic distance was all 0.020 or less in the COI and 18S rRNA gene sequences of 4 cheyletid mites species, with inter-species genetic distance of 0.235 to 0.583 and 0.078 to 0.114, respectively. Phylogenetic analysis based on COI and 18S rRNA genes showed that all four species of cheyletid mites were clustered into a branch with a 100% supportive rate, which was consistent with the morphological identification. Conclusion Mitochondrial COI gene is superior to 18S rRNA gene as DNA barcodes for 4 species of cheyletid mites, which is more suitable to be used to investigate the phylogenetic relationship of at genus and species levels.

AIM To study the effects of Elemene Injection (ELE) on the kinetics of intracellular transport of Gefitinib (GEF) in PC-9/GR cells and to probe the role of ELE in reversing oncological multidrug resistance.METHODS The intracellular pharmacokinetic behavior of D-luciferin potassium salt,a substrate of an ATP-binding cassette (ABC) protein,was investigated in PC-9/GRFluc cells using real-time bioluminescence imaging.The resistance of PC-9/GR cells to GEF was determined by MTT assay.Compusyn software was used to analyze the synergistic effect of GEF and ELE,and HPLC to detect the uptake of GEF in PC-9/GR cells.RESULTS The respective GEF IC50 values of 0.01 μg/mL in PC-9 cells and 1.50 μg/mL in PC-9/GR cells revealed the 150 times drug resistance of PC-9/GR to PC-9 cells.The significantly enhanced intracellular fluorescence intensity of D-fluorescein potassium salt by the intervention of ELE also indicated remarkable GEF uptake increase in PC-9/GR cell line (P ＜ 0.05) due to the synergistic result.CONCLUSION Partly as the mechanism in reversing oncological multidrug resistance,ELE,a booster for the fluorescence intensity of D-luciferin potassium salt,promotes cellular uptake of GEF by inhibiting efflux function of ABC proteins.

In this study, we isolated and purified the extracts of the whole plant of Crotalaria sessiliflora L. by column chromatographic. Twelve compounds were isolated and identified as followings: sessiliflorin B (1), quercetin (2), kaempferol (3), soyasapogenol B (4), fernenol (5), neoechinulin A (6), ethyl 4-hydroxybenzoate (7), ethyl caffeate (8), 5,7-dihydroxychromone (9), crotadihydrofuran A (10), butesuperin B (11) and aurantiamide acetate (12). Compound 1 is a new compound, compound 3-12 were isolated from the plant for the first time.

OBJECTIVETo explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy.

METHODSData were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed.

RESULTSFour syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters.

CONCLUSIONSExcess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

Capillaries ; Fibrosis ; Glomerulonephritis, IGA ; pathology ; Glomerulosclerosis, Focal Segmental ; Humans ; Kidney Glomerulus ; Medicine, Chinese Traditional ; Prognosis ; Syndrome