Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Objective To discuss the value of diffusion-weighted MRI (DWI) and 18F-FDG-PET/CT in assessing the early therapeutic effect of radiofrequency ablation (RFA) for VX2 sarcomas in experimental rabbits. Methods VX2 sarcoma was inoculated at bilateral hind limbs in 14 New Zealand white rabbits to establish the animal models. The implanted VX2 tumor on one hind leg was treated with ultrasound-guided percutaneous RFA (study group), while no RFA was given to the VX2 tumor on the contralateral hind leg (control group). DWI-MRI was performed at 2 days after RFA, and 18F-FDG-PET/CT examination was employed at 3 days after RFA. The mean apparent diffusion coefficient (ADC) values and standard uptake value (SUV) of the untreated tumor and the ablated tumor were separately calculated. Taking the pathologic result as the gold standard, the consistency of DWI-MRI, PET/CT as well as the combination of DWI-MRI and PET/CT with the clinical diagnosis was separately evaluated by Kappa test. Results Before RFA, DWI-MRI demonstrated that the VX2 tumor was characterized by hypo-intensity signal on T1 and hyper-intensity signal on T2 with ring-shaped enhancement on T1-weighted image; PET/CT showed that the tumor had nodular or ring-shaped 18F-FDG accumulation. After RFA, DWI-MRI revealed that the VX2 tumor was manifested as hyper-intensity signal on T1 and slight higher density on T1 with slight enhancement on contrast-enhanced T1-weighted image; PET/CT showed lowered accumulation of 18F-FDG. The mean ADC value of the ablated tumor was (1.52 ± 0.24) × 10-3 mm2/s, which was obviously higher than that of the un-ablated tumor, that was (1.09 ± 0.12) × 10-3 mm2/s, the difference was statistically significant(P<0.05). The mean SUV value of the ablated tumor was (0.6 ± 0.3), which was significantly lower than that of the ablated tumor (9.6 ± 3.2, P<0.05). No significant difference in sensitivity, specificity and accuracy existed between DWI-MRI and pathology as well as between PET/CT and pathology, the Kappa value being 0.357 and 0.428 respectively (P>0.05). The Kappa value of the consistency between combination of DWI-MRI with PET/CT and pathology was 0.786, which was significantly different from the result by simple DWI-MRI or simple PET/CT evaluation (P< 0.05). Conclusion Both ADC value of DWI-MRI and SUV value of PET/CT are useful indexes for evaluating the early therapeutic effect of RFA. Both DWI-MRI and PET/CT have their respective advantages, nevertheless, combination use of both can effectively improve the evaluation of curative effect for VX2 tumor after RFA in experimental rabbits.

OBJECTIVETo study the role of dietary and nutritional factors in the etiology of urolithiasis.

METHODSTwo hundred and fourty-one pairs of urolithiasis patients and controls were selected, and matched on age and sex, and without having urinary, endocrine, metabolic, or other related diseases. Subjects were given with a standardized semi-quantitative questionnaire to inquire their demographic features and diet information. Data were analyzed according to their respective property. Conditional logistic regression were used to compute odds ratio and 95% confidence interval.

RESULTSThe following variables were found to have significant in single factor logistic regression analysis: do not fond of drinking water [OR(no:yes) = 1.914 (95% CI: 1.272 - 2.881)]; drinking less purified water [OR(once:more) = 0.771 (95% CI: 0.614 - 0.967)]; drinking less liquid [OR(one cup more) = 0.273 (95% CI: 0.076 - 0.978)]; eating salted food [OR(highest:common) = 3.382 (95% CI: 2.133 - 5.362), OR(higher:common) = 1.435 (95% CI: 1.252 - 1.645)]; fond of sweet food [OR(most:no) = 4.509 (95% CI: 2.457 - 8.277), OR(more:no) = 1.562 (95% CI: 1.305 - 1.870)]; intake of animal oil [OR(yes:no) = 2.222 (95% CI: 1.012 - 4.880)]; over intake of protein, fat and phosphorus; less intake of carbohydrate, dietary fibre and vitamin C.

CONCLUSIONResults indicated that dietary and nutritional factors were important risk factors to the etiology of urinary calculi.

Ascorbic Acid ; administration & dosage ; Case-Control Studies ; Diet ; Drinking ; Humans ; Logistic Models ; Nutritional Physiological Phenomena ; Risk Factors ; Urinary Calculi ; etiology

Objective To establish an HPLC quantitative method for the content determination of baicalin in Kangdeling capsule .Methods The chromatography column was Agilent Tc-C18-WR (4 .6 mm × 250 mm ,5μm) ,and the column temper-ature was 30 ℃ .The mobile phase consisted of acetonitrile and 0 .5‰ phosphoric acid (26 ∶ 74 ) .The flow rate was 1 .0 ml/min ,and the detection wavelength was 265 nm .Results The retention time of baicalin was about 16 min .The calibra-tion equation was Y=22 114 .67 X -112 836 .7(r=0998 8)with good linearity in the range of 5 .410-108 .2 μg/ml for baicalin . The average recovery was 98 .78% while RSD were 0 .74% .Conclusion This method is simple ,time-saving and accurate which could be used to routine analysis of baicalin in Kangdeling capsule .

OBJECTIVE: To assess clinical value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for differentiation of malignant from benign focal thyroid incidentaloma. MATERIALS AND METHODS: This retrospective study included 99 patients with focal thyroid incidentaloma of 5216 non-thyroid cancer patients that had undergone PET/CT. PET/CT semi-quantitative parameters, volume-based functional parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of thyroid incidentaloma were assessed. Receiver-operating characteristic (ROC) analysis was conducted and areas under the curve (AUC) were compared by Hanley and McNeil test to evaluate usefulness of maximum standardized uptake value (SUVmax), MTV and TLG, as markers for differentiating malignant from benign thyroid incidentalomas. RESULTS: Of 99 thyroid incidentalomas, 64 (64.6%) were malignant and 35 (35.4%) were benign. Malignant thyroid incidentalomas were larger (1.8 cm vs. 1.3 cm, p = 0.006), and had higher SUVmax (11.3 vs. 4.8, p < 0.001), MTV (all p < 0.001) and TLG (all p < 0.001) than benign. TLG 4.0 had the highest performance for differentiation of malignant from benign thyroid incidentaloma in all semi-quantitative parameters with AUC 0.895 by ROC curve analysis. AUC (TLG 4.0) was significantly larger than AUC (SUVmean), AUC (MTV 2.5), AUC (MTV 3.0), AUC (MTV 3.5), AUC (TLG 2.5), and AUC (TLG 3.0), respectively (all, p < 0.05). There was no statistical difference between AUC (TLG 4.0) and AUC (SUVmax) (p > 0.05). A threshold TLG 4.0 of 2.475 had 81.3% sensitivity and 94.3% specificity for identifying malignant thyroid incidentalomas. CONCLUSION: Volume-based PET/CT parameters could potentially have clinical value in differential diagnosis of thyroid incidentaloma along with SUVmax.
Area Under Curve ; Diagnosis, Differential ; Electrons ; Fluorodeoxyglucose F18* ; Glycolysis ; Humans ; Positron-Emission Tomography and Computed Tomography* ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Thyroid Gland* ; Thyroid Neoplasms ; Tumor Burden

Fusobacterium nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. The two-component system plays an important role in the regulation and expression of genes related to pathogenic resistance and pathogenicity. In this paper, we focused on the CarRS two-component system of F. nucleatum, and the histidine kinase protein CarS was recombinantly expressed and characterized. Several online software such as SMART, CCTOP and AlphaFold2 were used to predict the secondary and tertiary structure of the CarS protein. The results showed that CarS is a membrane protein with two transmembrane helices and contains 9 α-helices and 12 β-folds. CarS protein is composed of two domains, one is the N-terminal transmembrane domain (amino acids 1-170), the other is the C-terminal intracellular domain. The latter is composed of a signal receiving domain (histidine kinases, adenylyl cyclases, methyl-accepting proteins, prokaryotic signaling proteins, HAMP), a phosphate receptor domain (histidine kinase domain, HisKA), and a histidine kinase catalytic domain (histidine kinase-like ATPase catalytic domain, HATPase_c). Since the full-length CarS protein could not be expressed in host cells, a fusion expression vector pET-28a(+)-MBP-TEV-CarS_cyto was constructed based on the characteristics of secondary and tertiary structures, and overexpressed in Escherichia coli BL21-Codonplus(DE3)RIL. CarS_cyto-MBP protein was purified by affinity chromatography, ion-exchange chromatography, and gel filtration chromatography with a final concentration of 20 mg/ml. CarS_cyto-MBP protein showed both protein kinase and phosphotransferase activities, and the MBP tag had no effect on the function of CarS_cyto protein. The above results provide a basis for in-depth analysis of the biological function of the CarRS two-component system in F. nucleatum.
Humans ; Histidine Kinase/metabolism* ; Fusobacterium nucleatum/metabolism* ; Automobiles ; Protein Kinases/genetics* ; Escherichia coli/metabolism* ; Colorectal Neoplasms