Objective:To investigate the expression characteristics and clinical significance of FOXC1 in colon cancer,and decipher its mo-lecular mechanism in regulating tumor cell proliferation and apoptosis.Methods:The GEPIA database was employed to analyze the expres-sion of FOXC1 and its correlation with prognosis in colon cancer.Differential expression of FOXC1 was detected by qRT-PCR and Western blot in colon cancer cells(HCT116 and SW620)and normal colon epithelial cells(NCM460),and stable FOXC1-knockdown(sh-FOXC1)cell lines were established.Western blot,flow cytometry,CCK-8,and plate colony formation assays were performed to analyze the effects of FOXC1 knockdown on cell proliferation,cell cycle,and apoptosis.Furthermore,the downstream signaling pathway was verified using Rap1 overexpression rescue experiments.Results:FOXC1 mRNA expression was significantly higher in colon cancer tissues than in normal tissues(P<0.001).FOXC1 overexpression was nearing significance in relation to tumor staging(P=0.053),and patients with high FOXC1 expression had a shorter overall survival(Log-rank P=0.013).After FOXC1 knockdown,the expression of CyclinD1 and Bcl-2 decreased,whereas the ex-pression of Bax increased(P<0.01).The proportion of cells in the G0/G1 phase increased,while the proportion of cells in the S phase de-creased(P<0.001),and the cell proliferation activity and number of colonies formed decreased(P<0.001).Mechanistic studies demonstrated that after FOXC1 knockdown,Rap1 expression was reduced,while the expression of Rap1GAP increased(P<0.05).After restoration of Rap1 expression in FOXC1-knockdown cells,the downregulation of CyclinD1 and Bcl-2 expression and the increase in Bax expression were re-versed(P<0.05),the S phase ratio was increased(P<0.05),and cell proliferation activity and colony formation abilities were also re-scued.Conclusion:FOXC1 promotes colon cancer progression by facilitating Rap1 expression and downregulating Rap1GAP.Targeted inter-vention of the FOXC1-Rap1 signaling axis may emerge as a potential therapeutic strategy.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To explore the prediction efficiency of Ki-67 expression status in pituitary adenoma(PA)based on a joint model of siamese network and transfer learning.Methods The preoperative MR T1WI enhanced sequence images of 370 patients with PA diagnosed by surgery and pathology were retrospectively collected.According to the results of immunohistochemical,all patients were divided into high proliferation index group(Ki-67≥3,n=97)and low proliferation index group(Ki-67＜3,n=273),and all the sample data were randomly divided into training set and test set according to the ratio of 7∶3.Two single predictive models,ResNet-50 and VGGNet-16 and combined them with the siamese network and transfer learning were built.The prediction efficiency of different models were evaluated via accuracy rate,precision rate,recall rate,F1 score and receiver operating characteristic(ROC)curve as the main criteria.Results Compared with a single predictive model,the model combined with siamese network and transfer learning showed a better performance for predicting the Ki-67 of PA.Additionally,the ResNet-50 joint model exhibited the superior predictive performance.The accuracy rate was 0.872 7,the precision rate was 0.812 5,the recall rate was 0.764 7,the F1 score was 0.787 9,and the area under the curve(AUC)was 0.841 6.Conclusion The joint model based on siamese network and transfer learning exhibits a higher efficiency for predicting the Ki-67 expression status in PA,which can help the clinicians to formulate more personalized treatment for the patients.

Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective:To analyze the incidence, mortality, survival patterns, and distribution characteristics of modifiable risk factors for colorectal cancer in selected global regions.Methods:Secondary analysis was conducted using data from the GLOBOCAN database and previous literature. We described the number of cases and age-standardized rates (ASRs) of incidence and mortality for colorectal cancer in China, the United States, the United Kingdom, and globally in 2022 and 2020, with gender-stratified analysis. ASRs were calculated using Segi's world standard population. Temporal trends in 5-year net survival rates were compared across three periods (2000-2004, 2005-2009, 2010-2014) among countries. Regional distribution differences in colorectal cancer deaths attributable to modifiable risk factors by gender were assessed in China.Results:In 2022, global colorectal cancer incidence and mortality were estimated at 1.926 million new cases and 904 000 deaths. China accounted for 27% of both global incidence (517 000 cases) and mortality (240 000 deaths). China's age-standardized incidence rate (20.1 per 100 000) was lower than those of the United States (27.0 per 100 000) and the UK (30.9 per 100 000). However, China's mortality rate (8.6 per 100 000) exceeded that of the US (7.9 per 100 000) but was lower than the UK (11.8 per 100 000). Compared to 2020, China demonstrated significant mortality reductions in 2022: males declined from 14.8 to 10.9 per 100 000, females from 9.4 to 6.5 per 100 000. Five-year net survival rates in China improved across periods for colon cancer (51.4%, 55.6%, 57.6%) and rectal cancer (49.5%, 52.5%, 56.9%), yet remained consistently lower than US and UK rates. Modifiable risk factors contributed to 45.1% of male and 41.4% of female colorectal cancer deaths in China, with marked regional disparities.Conclusions:China exhibits higher colorectal cancer incidence and mortality than global averages, with survival gaps persisting compared to developed nations. Regionally tailored comprehensive prevention strategies are essential to reduce disease burden through risk factor modification and optimized clinical management.

Objective To explore the feasibility of endovascular intervention technology for constructing canine models of hepatic vein(HV)obstruction type Budd-Chiari syndrome(BCS).Methods HV obstruction type BCS models were established through double approaches including external jugular vein and percutaneous transhepatic vein puncture,blocking the main HV with double balloon and injecting anhydrous ethanol using 10 Beagle dogs.Laboratory indexes before and after modeling were compared.Liver ultrasound was performed 2,4 and 8 weeks after modeling,respectively,while intravascular ultrasound(IVUS)and digital subtracting angiography(DSA)were performed after the last time ultrasound to observe the obstruction degree,lumen and blood flow of left hepatic vein(LHV).The stenosis rate of LHV was evaluated based on DSA findings,and successful establishment of HV obstruction type BCS canine model was regarded as stenosis rate＞30%and incomplete occlusion of LHV,then the success rate of modeling was recorded.Results No significant difference of laboratory indexes was found before and after modeling(all P＞0.05).Ultrasound,IVUS and DSA showed that after modeling,different degrees of LHV stenosis complicated with intrahepatic collateral circulation were found in 9 dogs,while complete occlusion of LHV was noticed in 1 dog.The success rate of modeling was 90.00%(9/10).Pathological results showed the target HV lumen narrow with thickened endovascular wall,and the latter mainly composed of fibroblast and collagen fiber proliferation.Conclusion Endovascular intervention technology was feasible for constructing canine models of HV obstruction type BCS.

Objective To systematically summarize medication patterns and explore the potential mechanisms of core herbal combinations in treating chronic glomerulonephritis(CGN)based on data mining and network pharmacology,and to provide a reference for clinical treatment strategies.Methods Electronic book databases were searched to screen the CGN prescription from the works of contemporary Xin'an medical practitioners.Frequency statistics,association rule analysis,and clustering algorithms via the traditional Chinese medicine(TCM)Inheritance Support Platform V3.5 were applied to identify high-frequency herbs(frequency of use>10%)and core combinations.Active ingredients and potential targets were predicted using TCMSP,PubChem,and SwissTargetPrediction databases.Disease-related targets were retrieved from OMIM and GeneCards,after obtaining the intersecting targets,followed by protein-protein interaction(PPI)network construction(STRING platform),Cytoscape topological analysis,and GO and KEGG pathway enrichment(DAVID).Results A total of 151 prescriptions related to the treatment of CGN were included,involving 213 flavours of TCM,including 42 varites of high frequency drugs,mainly in the categories of supplementing deficiency,eliminating dampness and diuresis and clearing heat.Theherb properties were mainly cold,warm,and neutral,with flavors of sweet,bitter,and pungent.Herbs primarily targeted the liver,lung,kidney,and spleen meridians.Thecore combination"Astragali Radix,Dioscorea Rhizome,Atractylodis Macrocephalae Rhizoma,Imperata Rhizome,Pyrrosiae Folium,Poria"was identified,with key active ingredients including quercetin,stigmasterol,and β-sitosterol.Core targets involved IL6,EGFR,TNF,AKT1,and PIK3CA,while enriched pathways included PI3K-Akt and AGE-RAGE signaling.Conclusion Contemporary Xin'an practitioners primarily treat CGN by tonifying the spleen,nourishing the kidney,and clearing damp-heat.Thecore herbal combination exerts synergistic effects through multi-target intervention in immune-inflammatory pathways,oxidative stress,and fibrotic pathways,highlighting the holistic therapeutic advantages of TCM formulas via multi-component synergistic regulation and multi-target interactions.This study provides a theoretical foundation for further experimental validation and clinical applications.