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 investigate the epidemiological trends of viral diarrhea pathogens in children in Baotou city, and to provide reference for controlling the prevalence of viral diarrhea and guiding the development of regional vaccines.Methods:Fecal samples were collected from children under five years old hospitalized with viral diarrhea at two sentinel hospitals in Baotou from June 2023 to May 2024. Real-time PCR was used to detect group A rotavirus, norovirus, adenovirus, and astrovirus. Statistical analysis was performed using SPSS 20.0 software, with Chi-square tests conducted to assess differences. A P value<0.05 was considered statistically significant. Results:A total of 246 fecal samples were collected, including 153 from males and 93 from females. Among these, 135 samples tested positive, yielding a positivity rate of 54.88% (135/246). There were 82 positive samples from male children and 53 from female children, with no significant difference between genders. Most positive samples (51.85%, 70/135) tested positive for two viruses. Specifically, co-infections of group A rotavirus with norovirus or adenovirus accounted for 98.57% (69/70) of all co-infected cases. Significant differences in detection rates were observed across age groups (χ 2=29.803, P<0.001), with the highest positivity rates in children under one year old and in the 1-year age group. Seasonality, viral diarrhea in Baotou was more prevalent in winter and spring. The G8P[8] genotype of group A rotavirus was the predominant strain. Conclusions:From June 2023 to May 2024, viral diarrhea in hospitalized children under five years old in Baotou is primarily caused by co-infections of group A rotavirus and norovirus, with a higher incidence in preschool-aged children. The G8P[8] genotype of group A rotavirus is the dominant strain. It is recommended to strengthen vaccination and surveillance efforts for viral diarrhea in preschool children, particularly during the winter and spring seasons.

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 investigate the epidemiological trends of viral diarrhea pathogens in children in Baotou city, and to provide reference for controlling the prevalence of viral diarrhea and guiding the development of regional vaccines.Methods:Fecal samples were collected from children under five years old hospitalized with viral diarrhea at two sentinel hospitals in Baotou from June 2023 to May 2024. Real-time PCR was used to detect group A rotavirus, norovirus, adenovirus, and astrovirus. Statistical analysis was performed using SPSS 20.0 software, with Chi-square tests conducted to assess differences. A P value<0.05 was considered statistically significant. Results:A total of 246 fecal samples were collected, including 153 from males and 93 from females. Among these, 135 samples tested positive, yielding a positivity rate of 54.88% (135/246). There were 82 positive samples from male children and 53 from female children, with no significant difference between genders. Most positive samples (51.85%, 70/135) tested positive for two viruses. Specifically, co-infections of group A rotavirus with norovirus or adenovirus accounted for 98.57% (69/70) of all co-infected cases. Significant differences in detection rates were observed across age groups (χ 2=29.803, P<0.001), with the highest positivity rates in children under one year old and in the 1-year age group. Seasonality, viral diarrhea in Baotou was more prevalent in winter and spring. The G8P[8] genotype of group A rotavirus was the predominant strain. Conclusions:From June 2023 to May 2024, viral diarrhea in hospitalized children under five years old in Baotou is primarily caused by co-infections of group A rotavirus and norovirus, with a higher incidence in preschool-aged children. The G8P[8] genotype of group A rotavirus is the dominant strain. It is recommended to strengthen vaccination and surveillance efforts for viral diarrhea in preschool children, particularly during the winter and spring seasons.

Objective This study utilized bioinformatics to investigate the role of secreted phosphoprotein 1(SPP1)in tumors and assess its differential expression and prognostic significance across human cancers.Method Cancer sample data was sourced from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database.Analysis of gene expression differences in pan-cancer involving SPP1 utilized the CPTAC database,correlations between SPP1 and patient survival outcomes were assessed using GEPIA2,and alterations in gene mutations for SPP1 across 32 cancers were appraised via the CbioPortal tool.Results Across 32 tumor types,SPP1 mRNA disparity is observed in eight cancer types,decreasing only in clear cell renal carcinoma while increasing in other malignancies.Expression in tumor stage is specific;SPP1 mRNA negatively correlates with patient overall survival(OS)and disease-free survival(DFS);low methylation associated with SPP1 gene activity promotes oncogene activation,impacting tumor cell generation,apoptosis,and proliferation,thereby influencing cancer progression;SPP1 primarily exhibits missense mutations that correlate with poor prognoses in prostate and stomach cancer patients.Conclusion Through pan-cancer studies,SPP1's selective expression in human malignancies was validated and found to be strongly correlated with clinical prognosis.This suggests that SPP1 is a viable target for cancer prognostic precision.

Objective To utilize bioinformatic approaches to elucidate the correlation between secreted phosphoprotein 1(SPP1)and immune infiltration in various malignancies,elucidating the mechanism of gene function in cancer-immune cell interplay.Methods Cancer samples were derived from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database,examining SPP1 expression difference between tumors and normal tissues using Gene Expression Profiling Interactive Analysis(GEPIA2),and its correlation with different immune cells in extracellular matrix via TIMER2 Database.SPP1's association with interacting molecules was scrutinized on the STRING website,followed by assessment of its distinct functional state across various cancers from Cancer Single-cell State Atlas Database(Cancer SEA).Results In 32 tumor types,SPP1 mRNA is significantly elevated in 23 types of cancers and correlates heavily with fibroblast,integrin family,and CD44.Furthermore,the SPP1 gene exhibits profound specificity in tumor functions such as vascular invasion,metastasis,DNA damage,and repair.Conclusion Specific expression of SPP1 in tumors signifies a significant correlation with tumor immune cells in the extracellular matrix,promoting tumor progression and invasion.This suggests that targeted monitoring of SPP1 could serve as a prospective cancer diagnostics/therapeutics biomarker.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Objective To improve the performance of auto-segmentation of prostate target area and organs-at-risk in online magnetic resonance image and enhance the efficiency of magnetic resonance imaging-guided adaptive radiotherapy(MRIgART)for prostate cancer.Methods A retrospective study was conducted on 40 patients who underwent MRIgART for prostate cancer,including 25 in the training set,5 in the validation set,and 10 in the test set.The planning CT images and corresponding contours,along with online MR images,were registered and input into a deep learning network for online MR image auto-segmentation.The proposed method was compared with deformable image registration(DIR)method and single-MR-input deep learning(SIDL)method.Results The overall accuracy of the proposed method for auto-segmentation was superior to those of DIR and SIDL methods,with average Dice similarity coefficients of 0.896 for clinical target volume,0.941 for bladder,0.840 for rectum,0.943 for left femoral head and 0.940 for right femoral head,respectively.Conclusion The proposed method can effectively improve the accuracy and efficiency of auto-segmentation in MRIgART for prostate cancer.