Objective To explore the effects of CYP2C19, CYP2C9 and CYP3A5 genotypes on the plasma concentration of voriconazole in children. Methods Collected blood samples from 50 hospitalized children with invasive fungal infections who received intravenous voriconazole from January 2020 to December 2020. High performance liquid chromatography was used to detect the blood trough concentration of voriconazole, and the time-of-flight mass spectrometry detection system was used to detect the genotypes of CYP2C19, CYP2C9 and CYP3A5, and the effects of children’s genotyping on the plasma concentration, efficacy and adverse reactions of voriconazole were analyzed. Results The total effective rate of 50 children with IFI was 84% （42/50 cases） after voriconazole treatment. The incidence of adverse reactions was 20% （10/50 cases）. The measured plasma concentration of voriconazole ranged from 0.56~7.62 μg/ml. Combined with the different mutation types of CYP2C19 gene loci, three metabolic activities were produced: fast, medium and slow, and the test results showed that there were 16 cases of fast metabolism, 27 cases of intermediate metabolism and 7 cases of slow metabolism. There was a significant difference in plasma concentrations among the three groups （F=15.359, P<0.001）, and the drug concentrations in the fast metabolic group were significantly lower than those in the intermediate metabolic and slow metabolic groups. The mutations of CYP2C9 and CYP3A5 had no significant effect on the plasma concentrations of the drugs, which were （F=2.213, P=0.086 and F=0.757, P=0.475）. Conclusion Voriconazole had significant efficacy in the treatment of invasive fungal infections in children, and the adverse reactions were mild. CYP2C19 genotype was significantly related to the rate of drug metabolism and was an important factor affecting blood drug concentration, the detection of drug concentration and genotype of voriconazole was helpful to adjust the effective drug dose clinically and would achieve more scientific and individualized treatment.

ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC₅₀ value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Objective To carry out a joint simulation exercise of tabletop deduction for the staff performing overseas medical services on hospital ships,so as to improve the infection prevention and control.Methods Sixty mission members were selected by convenience sampling to carry out joint simulation drills for tabletop deduction.The effects of the drills were assessed by the survey on the satisfaction and participation of mission members,before-and-after control study,and mission execution.Results Overseas medical service tasks were successfully completed through the desktop-propelled joint simulation drills.The total score of response for infectious emergencies,prevention score,preparedness score,and rescue score after training were higher than those before training(P<0.05).There were high degrees of participation and satisfaction in the drills(≥4.5 points).Conclusion The tabletop deduction and simulation exercise achieve good results in the infection prevention and control of hospital ships.The scheme of tabletop deduction combined with simulation drills will be optimized to continuously improve the infection prevention and control of hospital ships.

Objective To investigate the epidemiological characteristics and influencing factors of Femoral Artery Compression-Related Skin Complications Around the Puncture Site(FACR-SCAPS)in patients with primary hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).Methods A multicenter cross-sectional study was conducted using convenience sampling.A total of 1 573 HCC patients who underwent TACE between April 2023 and October 2024 were recruited from interventional radiology departments,oncology units,and specialized centers across 10 hospitals in Beijing,Tianjin,Shandong,Hebei,Qinghai,and Inner Mongolia.Descriptive statistics,univariate analysis,and multivariate logistic regression were used to explore the epidemiological characteristics and influencing factors of FACR-SCAPS in this population.Results Among the 1 573 primary HCC patients undergoing TACE interventional therapy,FACR-SCAPS occurred in 28.99％(456/1 573),with a total of 476 complication instances recorded(30.26 per 100 patients).Patients with a single complication accounted for 96.93％,whereas those with multiple complications constituted 3.07％.The most prevalent types of complications were skin erythema,skin ecchymosis,and hard lumps formation,collectively accounting for 96.49％of all complications.Hematoma,blisters,and rupture complications collectively accounted for only 4.61％.Logistic regression analysis revealed that peak diastolic blood pressure during compression(OR=1.024,95％CI:1.013-1.035,P＜0.001),use of rotary compression hemostasis devices(OR=3.220,95％CI:2.120-4.891,P＜0.001),elevated PT-INR(OR=19.630,95％CI:6.039-63.810,P＜0.001),and anticoagulant use within the last three months(OR=1.909,95％CI:1.064-3.427,P=0.030)were significant influencing factors associated with FACR-SCAPS post-TACE.Conclusion FACR-SCAPS is commonly seen among primary HCC patients after TACE,its risk factors include peak diastolic blood pressure during compression,use of rotary compression devices,elevated PT-INR,and recent anticoagulant use.

Objective To study the pathogenic bacteria infection in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province and its correlation with different Wagner grades,to understand the the characteristics of pathogenic bacteria and related risk factors in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province,and to further provide theoretical guidance for anti-infection treatment of these patients.Methods A retrospective analysis was conducted on the demographic data,severity of foot ulcers,and related laboratory test results of 536 patients with diabetic foot who were detected to have bacterial infection in the Third People's Hospital of Yunnan Province from January 2019 to January 2023.Results Among the 536 diabetic foot patients,pathogenic bacteria were cultured from 268 cases(50.0%)of Gram-positive bacterial infections,214 cases(39.9%)of gram-negative bacterial infections,2 cases(0.4%)of fungal infections,and 52 cases(9.7%)of mixed bacterial infections.The main pathogens among gram-positive bacteria were Staphylococcus aureus,Staphylococcus epidermidis and Enterococcus faecalis.for Gram-negative bacteria,the main pathogens were Escherichia coli,Enterobacter cloacae and Klebsiella pneumoniae.There were 31 cases of multi-drug resistant bacteria,and the multi-drug resistance rate was(5.78%).Among Gram-positive bacteria,all multidrug-resistant strains were Staphylococcus aureus,while among Gram-negative bacteria,the multi-drug resistant strains included Acinetobacter baumannii(1 case),Klebsiella pneumoniae(2 cases),Proteus common(2 cases),Pseudomonas aeruginosa(5 cases),Proteus mirabilis(1 case)and Enterobacter cloacae(1 case).The 536 patients were divided into Wagner grade 1 and 2 groups(78 cases),Wagner grade 3 group(274 cases),and Wagner grade 4 and 5 groups(184 cases).There were 73 cases of single bacterial infections and 5 cases of mixed bacterial infections in Wagner grade 1 and 2 group,including 51 cases(65.4%)of gram-positive bacteria,21 cases(26.9%)of gram-negative bacteria and 1 case(1.3%)of fungi.There were 248 cases of single bacterial infections and 26 cases of mixed bacterial infections in Wagner3 group,with 144 cases(52.6%)of gram-positive bacteria,103 cases(37.6%)of gram-negative bacteria,and 1 case(0.4%)with fungi.In the Wagner grade 4 and 5 groups,there were 163 cases of single bacterial infections and 21 cases of mixed bacterial infection,with 73 strains(39.7%)of gram-positive bacteria,90 strains(48.9%)of gram-negative bacteria and 0 strain(0%)of fungi.The predominant infectious pathogens in Wagner grades 1,2 and 3 were gram-positive bacteria,while those in Wagner grades 4 and 5 patients were mainly gram-negative bacteria.There were statistically significant differences in white blood cell counts,neutrophil percentage,bacterial classification,length of hospital stay,erythrocyte sedimentation rate and albumin levels among diabetic foot patients with different Wagner grades(P<0.01).With the increase of Wagner grade,patients had higher white blood cell counts and hypersensitive C-reactive protein levels,longer hospital stays,and lower albumin levels;however,there were no statistically significant differences in age,sex,duration of diabetes,smoking history,alcohol consumption history and history of hypertension(P>0.05).Conclusion The bacterial infection situation in patients with diabetic foot ulcers is related to different Wagner grades.The higher the Wagner grades,the greater the likelihood of infection with gram-negative bacteria.Antibiotics can be reasonably selected according to the Wagner grades of patients upon admission,actively controlling infection,while also enhancing,shortening hospital stays,and reducing amputation rates,thereby improving the prognosis of diabetic foot patients.

Objective To analyze the bacterial distribution characteristics,drug resistance characteristics and related risk factors of multidrug-resistant organisms(MDRO)in patients with diabetic foot infection(DFI)in some areas of Yunnan Province to provide empirical reference for clinical treatment.Methods Clinical data of 300 DFI patients admitted to the Department of Endocrinology of the Third People's Hospital of Yunnan Province from January 2019 to December 2023 were collected.Based on the results of drug sensitivity tests and matching of basic data,patients were divided into the MDRO group(n=60)and the non-MDRO group(n=240).A retrospective analysis was conducted on the distribution of pathogenic bacteria,drug resistance characteristics of MDRO and risk factors for MDRO infection in DFI patients.Results In 60 patients with MDRO infections,62 strains of MDRO were cultured,with 58 strains from single MDRO infections and 4 strains from mixed MDRO infections.Of the 60 patients,2 were cultured for 2 types of MDRO.Among the strains,there were 45 gram-positive bacteria(72.58％)which were all Staphylococcus aureus,17 strains of gram-negative bacteria(27.42％)mainly including Pseudomonas aeruginosa,Enterobacter cloacae and Klebsiella pneumoniae.Among common MDRO,Staphylococcus aureus showed complete resistance to penicillin G and oxacillin(100％),with high resistance to erythromycin and clindamycin(＞80％),but no resistance to tigacycline vancomycin was observed.The resistance of Klebsiella pneumoniae and Enterobacter cloacae to cephalosporin antibiotics was obvious,and the resistance rate to imipenem and amikacin was low.Pseudomonas aeruginosa was 100％resistant to ticacillin/clavulanate potassium,imipenem,tigacycline and cotrimoxazole,but showed no resistance to cefepime,ciprofloxacin,gentamicin and amikacin.There were statistically significant differences between the two groups in regional distribution,duration of diabetic foot,lower extremity arterial disease,venous plasma glucose levels and glycosylated hemoglobin(P＜0.05).Binary Logistic regression analysis showed that region and duration of diabetic foot disease were independent risk factors for MDRO infection in DFI patients(P＜0.05).Conclusion In some areas of Yunnan Province,the distribution of MDRO in DFI patients is mainly gram-positive bacteria,with varying antibiotic sensitivities among different pathogens.Multiple factors lead to MDRO infections in DFI patients,which assists clinical practitioners in early identification of high-risk DFI patients with MDRO infections and provide empirical reference for clinical treatment.

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 study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Taste is an important aspect that affects the application and development of oral liquid preparations of tradi-tional Chinese medicine,and bitterness is the main adverse taste of such preparations.In January 2024,the Chinese Society of Tra-ditional Chinese Medicine released the social organization standard"Technical Specification for Sensory Evaluation of Bitterness of Oral Liquid Preparation of Traditional Chinese Medicine"(standard number:T/CACM 1574-2024),led by the Chinese Medi-cine Preparation Branch of the Chinese Society of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,and Beijing University of Traditional Chinese Medicine,with the participation of 22 units nation-wide.It provided scientific guidance and good tools for the evaluation of bitterness of such preparations and lays a technical foun-dation for the subsequent implementation of taste improvement.This article provided a detailed introduction to the background and significance,formulation process,and main content of the standard development,which is beneficial for traditional Chinese medi-cine pharmacists to understand the standard better,apply,promote,and improve the group's standard,thereby promoting the im-provement of the taste quality and patient acceptance of such preparations,and promoting the development of the modernization of traditional Chinese medicine.