Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5％success rate),while in the CCS group,25 cases were successful(100.0％success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5％),while in the CCS group,three cases were observed(3/25;12.0％).Additionally,one case in the ACS group(1/22;4.5％)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P＞0.05).There was no significant difference in the MACE(9.1％vs.4.0％,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.

Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)％,(48.16±4.31)％,(85.31±5.83)％,(81.39±6.47)％and(58.75±5.24)％,respectively;cell apoptosis rates were(3.27±0.81)％,(41.26±2.09)％,(11.35±1.04)％,(10.29±1.26)％and(35.87±2.15)％,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P＜0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P＜0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P＜0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.

Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5％success rate),while in the CCS group,25 cases were successful(100.0％success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5％),while in the CCS group,three cases were observed(3/25;12.0％).Additionally,one case in the ACS group(1/22;4.5％)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P＞0.05).There was no significant difference in the MACE(9.1％vs.4.0％,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.

Abstract: Objective To analyze the antimicrobial resistance rate and risk factors of multi drug resistant organisms (MDRO) in bloodstream infection for rational treatment. Methods　A total of 696 cases of bloodstream infections of Staphylococcus aureus, Enterococcus, Enterobacteriaceae (excluding Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter in our hospital from 2017 to 2021 were selected, and 711 pathogenic strains were isolated from their whole blood samples. The antimicrobial resistance rates of various multi drug resistant strains were analyzed and the risk factors of MDRO infection were analyzed. Results　696 non repeated cases were screened out from 13 187 whole blood culture specimens, with a positive rate of 5.3%, and a total of 711 blood influenza pathogens were detected, among them, 350 strains of MDRO were detected with a detection rate of 49.23% (350/711). Among the pathogenic bacteria of bloodstream infection, Escherichia coli was the most, with 277 strains accounting for 38.96% (277/711), of which 201 strains were MDRO, accounting for 57.43% (201/350); followed by Klebsiella pneumoniae and Staphylococcus aureus, with 155 strains accounting for 21.80% (155/711) and 89 strains accounting for 12.52% (89/711), among which 43 strains of Klebsiella pneumoniae MDRO accounted for 12.29% (43/350) and 38 strains of Staphylococcus aureus MDRO accounted for 10.86% (38/350). The change trend of the three pathogens during 2017-2021 was not obvious. The drug sensitivity test showed that Escherichia coli and Klebsiella pneumoniae were highly resistant to cephalosporins and fluoroquinolones, and the drug resistance rate of aminoglycosides was relatively low. They had almost no resistance to cephalosporins and carbapenems. Staphylococcus aureus has a high resistance rate to lincomycin and macrolides, but no resistance to oxazolidinone, glycopeptides and glycylcyclins. There were 350 cases of MDRO infection and 361 cases of non MDRO infection. Univariate analysis showed that the age, sex, cardiovascular and cerebrovascular history, renal insufficiency, lung disease, hypoalbuminemia, hepatobiliary disease, electrolyte disorder and anemia of the patients had no statistical significance in MDRO infection (P>0.05); diabetes, urinary tract infection, surgical operation and burn were the influencing factors of MDRO (P<0.05). According to logistic analysis, diabetes, urinary tract infection, surgical operation and burn were the risk factors of MDRO infection (P<0.05). Conclusion　The infection of MDRO in patients with bloodstream infection is serious, and early prevention and control should be paid attention to, and the principle of graded use of antibiotics should be strictly observed, and the rational application should be carried out to actively and effectively control the production of MDRO.

Objective: To examine the effects of bisphenol A (BPA), bisphenol S ( BPS ), bisphenol F ( BPF ) and bisphenol AF ( BPAF ) on the proliferation and oxidative stress of BRL 3A rat liver cells, and to preliminarily evaluate their mutagenicities. Methods: In vitro cultured BRL 3A rat liver cells were treated with BPA, BPS, BPF and BPAF at concentrations of 0, 5, 10, 25, 50, 100, 150 and 200 μmol/L for 48 h, respectively. Then, the cell viability was determined using the CCK-8 assay, and the half maximal inhibitory concentration ( IC50 ) was calculated. The minimum inhibitory concentration for BRL 3A cell proliferation was screened, and the intracellular reactive oxygen species ( ROS ) was measured in BRL 3A cells using the 2',7'-dichlorodihydrofluorescein diacetate ( DCFH-DA ) assay. In addition, the effects of BPA, BPS, BPF and BPAF at concentrations of 1 000, 200, 40, 8 and 1.6 μg/plate on the mutant colonies of histidine-deficient Salmonella typhimurium ( TA1535, TA97a, TA98, TA100 and TA102 ) were tested using the Ames test. Results: Treatment with BPA and BPF at concentrations of 100 to 200 μmol/L and with BPAF at concentrations of 25 to 200 μmol/L inhibited BRL 3A cell survival at a concentration-dependent manner, while exposure to BPS at concentrations of 5 to 200 μmol/L resulted in no changes in BRL 3A cell survival. The IC50 values of BPA, BPS, BPF and BPAF were 131.7, >200, 187.5 and 21.6 μmol/L against BRL 3A cells, respectively. Treatment with BPS at 100 μmol/L or BPAF at 25 μmol/L caused no significant changes in the ROS level; however, exposure to BPA at 100 μmol/L and BPF at 100 μmol/L significantly increased the ROS level. Ames test showed that BPA, BPS, BPF and BPAF did not induce mutagenicity in TA1535, TA97a, TA98, TA100 or TA102 strains. Conclusions BPAF shows the highest cytotoxicity to BRL 3A cells, and low-concentration exposure to BPS has few effects on BRL 3A cells. The cytotoxicity of bisphenols against BRL 3A cells may be associated with the induction of oxidative stress. None of the four bisphenols show mutagenic effects under the present experimental conditions.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

This study aimed to explore the anti-depressant components of Rehmanniae Radix and its action mechanism based on network pharmacology combined with molecular docking. The main components of Rehmanniae Radix were identified by ultra-high performance liquid chromatography-quadrupole/Orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS), and the related targets were predicted using SwissTargetPrediction. Following the collection of depression-related targets from GeneCards, OMIM and TTD, a protein-protein interaction(PPI) network was constructed using STRING. GO and KEGG pathway enrichment analysis was performed by Metascape. Cytoscape 3.7.2 was used to construct the networks of "components-targets-disease" and "components-targets-pathways", based on which the key targets and their corresponding components were obtained and then preliminarily verified by molecular docking. Rehmanniae Radix contained 85 components including iridoids, ionones, and phenylethanoid glycosides. The results of network analysis showed that the main anti-depressant components of Rehmanniae Radix were catalpol, melittoside, genameside C, gardoside, 6-O-p-coumaroyl ajugol, genipin-1-gentiobioside, jiocarotenoside A1, neo-rehmannioside, rehmannioside C, jionoside C, jionoside D, verbascoside, rehmannioside, cistanoside F, and leucosceptoside A, corresponding to the following 16 core anti-depression targets: AKT1, ALB, IL6, APP, MAPK1, CXCL8, VEGFA, TNF, HSP90 AA1, SIRT1, CNR1, CTNNB1, OPRM1, DRD2, ESR1, and SLC6 A4. As revealed by molecular docking, hydrogen bonding and hydrophobicity might be the main action forms. The key anti-depression targets of Rehmanniae Radix were concentrated in 24 signaling pathways, including neuroactive ligand-receptor interaction, neurodegenerative disease-multiple diseases pathway, phosphatidylinositol 3-kinase/protein kinase B pathway, serotonergic synapse, and Alzheimer's disease.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Molecular Docking Simulation ; Network Pharmacology ; Neurodegenerative Diseases ; Plant Extracts ; Rehmannia