Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

BACKGROUND: Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS: In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. RESULTS: In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG ( P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm ( P  = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability ( P  = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure.
Humans ; Stomach Neoplasms/drug therapy* ; Gastrectomy/methods* ; Neoadjuvant Therapy/methods* ; Male ; Female ; Middle Aged ; Propensity Score ; Aged ; Adult ; Retrospective Studies

The in-depth research of artificial intelligence in the medical field has greatly improved the workflow and diagnostic ability of diagnostic radiology.This article focuses on artificial intelligence technology in the field of interventional medicine,and enumerates its potential application scenarios,including improving image analysis capabilities to assist diagnosis and predict treatment response.It also describes the challenges that need to be overcome for practical application.Finally,with the continuous development of artificial intelligence in interventional medicine,artificial intelligence will further optimize the channels of interventional medicine and bring revolutionary changes to the clinical practice of interventional medicine.

Objective:To construct a risk prediction model for Vaginal Intraepithelial Neoplasia Grade 2 or Worse(VaIN 2+)lesions,and to establish a nomogram for individual diagnosis of VaIN 2+and risk stratification,so as to provide guidance for the treatment of vaginal lesions.Methods:A total of 248 women diagnosed with VaIN through colposcopic biopsy at the Center for Gynecologic and Cervical Diseases,First Affiliated Hospital of Nanjing Medical University,from January 2021 to January 2024 were included in this study.Based on the gold standard established by histological and pathological findings,these patients were categorized into a lower VaIN 2 group and a VaIN 2+group.Univariate comparative analysis was performed on the two groups.Multivariate Logis-tic regression analysis was used to determine the risk factors of VaIN 2+and to construct a diagnostic model.The nomogram model was established by using R Studio software.The discrimination,calibration and clinical practical value of the model were evaluated by the area under the receiver operating characteristic(ROC)curve and cali-bration curve.Results:Univariate analysis identified that HPV type,cervical lesion grade,acetowhite change,vagi-nal lesion duration,vaginal lesion location,and cervical lesion duration as influencing factors for diagnosing VaIN 2+(P<0.1).Multivariate binary Logistic regression analysis indicated that HPV16/18 positivity,cervical lesion grade≥CIN 2,thick acetowhite change,vaginal lesion duration≥5 years,and vaginal lesion location at the upper 1/3 of the vagina were independent risk factors for diagnosing VaIN 2+(OR>1,P<0.05),while cervical lesion duration<3 years was a protective factor(OR<1,P<0.05),with acetowhite change having the greatest impact(OR4.54).A regression model was established based on the multivariate binary Logistic regression analysis,with an AUC of 0.813.A nomogram model was constructed and internally validated,yielding a consistency index(C-index)of 0.81.Patients were stratified into risk groups using the X-tile software,with higher total scores indi-cating a greater risk of developing VaIN 2+.Conclusions:The nomogram model constructed in this study can in-dividually predict the risk of VaIN 2+lesions in patients,with high accuracy and clinical practicability.

Objective:This study aims to analyze the economic impact of postoperative complications after colorectal cancer surgery.Methods:A retrospective cohort study was conducted. Patients with a preoperative pathological diagnosis of colorectal cancer who met surgical indications and underwent surgical treatment were included, while those with incomplete hospitalization cost data were excluded. From March 2017 to March 2022, three hundred and ninety-two colorectal cancer patients treated at Peking University Cancer Hospital and Institute Gastrointestinal Cancer Center I, were enrolled. Descriptive statistics were performed on the incidence of complications, hospitalization costs, and postoperative length of stay. A cohort was established based on the presence of postoperative complications (POC) and absence of postoperative complications (non-POC) to study economic differences. Propensity score matching analysis was employed to reduce potential confounding factors.Results:Among 392 colorectal cancer patients, 90 (23.0%) developed POC (POC group), while 302 were in the non-POC group. Significant statistical differences were found between the two groups in terms of operation duration, extent of resection, and stoma creation (all P < 0.05); other baseline indicators showed no significant differences (all P>0.05). The median hospitalization cost for patients with postoperative anastomotic leakage was 115 973 yuan, an increase of 38 941 yuan (50.5%) over the non-POC group's 77 059 yuan; the median hospitalization cost for patients with mechanical obstruction was 111 477 yuan, an increase of 34 418 yuan (44.7%) over the non-POC group; and the median hospitalization cost for patients with wound infection was 95 860 yuan, an increase of 18 801 yuan (24.4%) over the non-POC group. The median postoperative length of stay for patients with anastomotic leakage, mechanical obstruction, and wound infection was 22.0 days, 22.0 days, and 18.5 days, respectively, compared to 9.0 days in the non-POC group, extending by 13.0 days, 13.0 days, and 9.5 days. After propensity score matching, each group had 68 patients, and there were no statistically significant differences in preoperative and intraoperative observations between the two groups (all P>0.05); compared to the non-POC group, the hospitali- zation costs in the POC group significantly increased (89 165 yuan vs. 75 437 yuan, P<0.001), and the postoperative length of stay also significantly extended (14.0 days vs. 8.0 days, P<0.001). Conclusions:The occurrence of POC after colorectal cancer surgery significantly increases hospitalization costs and length of stay. This study provides specific and accurate reference data for subsequent health economic decision-making. This is the first detailed economic impact analysis of postoperative complications of colorectal cancer with a large sample size, which includes an economic impact analysis for each POC and subgroup.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Objective:This study aims to analyze the economic impact of postoperative complications after colorectal cancer surgery.Methods:A retrospective cohort study was conducted. Patients with a preoperative pathological diagnosis of colorectal cancer who met surgical indications and underwent surgical treatment were included, while those with incomplete hospitalization cost data were excluded. From March 2017 to March 2022, three hundred and ninety-two colorectal cancer patients treated at Peking University Cancer Hospital and Institute Gastrointestinal Cancer Center I, were enrolled. Descriptive statistics were performed on the incidence of complications, hospitalization costs, and postoperative length of stay. A cohort was established based on the presence of postoperative complications (POC) and absence of postoperative complications (non-POC) to study economic differences. Propensity score matching analysis was employed to reduce potential confounding factors.Results:Among 392 colorectal cancer patients, 90 (23.0%) developed POC (POC group), while 302 were in the non-POC group. Significant statistical differences were found between the two groups in terms of operation duration, extent of resection, and stoma creation (all P < 0.05); other baseline indicators showed no significant differences (all P>0.05). The median hospitalization cost for patients with postoperative anastomotic leakage was 115 973 yuan, an increase of 38 941 yuan (50.5%) over the non-POC group's 77 059 yuan; the median hospitalization cost for patients with mechanical obstruction was 111 477 yuan, an increase of 34 418 yuan (44.7%) over the non-POC group; and the median hospitalization cost for patients with wound infection was 95 860 yuan, an increase of 18 801 yuan (24.4%) over the non-POC group. The median postoperative length of stay for patients with anastomotic leakage, mechanical obstruction, and wound infection was 22.0 days, 22.0 days, and 18.5 days, respectively, compared to 9.0 days in the non-POC group, extending by 13.0 days, 13.0 days, and 9.5 days. After propensity score matching, each group had 68 patients, and there were no statistically significant differences in preoperative and intraoperative observations between the two groups (all P>0.05); compared to the non-POC group, the hospitali- zation costs in the POC group significantly increased (89 165 yuan vs. 75 437 yuan, P<0.001), and the postoperative length of stay also significantly extended (14.0 days vs. 8.0 days, P<0.001). Conclusions:The occurrence of POC after colorectal cancer surgery significantly increases hospitalization costs and length of stay. This study provides specific and accurate reference data for subsequent health economic decision-making. This is the first detailed economic impact analysis of postoperative complications of colorectal cancer with a large sample size, which includes an economic impact analysis for each POC and subgroup.

Objective:To construct a risk prediction model for Vaginal Intraepithelial Neoplasia Grade 2 or Worse(VaIN 2+)lesions,and to establish a nomogram for individual diagnosis of VaIN 2+and risk stratification,so as to provide guidance for the treatment of vaginal lesions.Methods:A total of 248 women diagnosed with VaIN through colposcopic biopsy at the Center for Gynecologic and Cervical Diseases,First Affiliated Hospital of Nanjing Medical University,from January 2021 to January 2024 were included in this study.Based on the gold standard established by histological and pathological findings,these patients were categorized into a lower VaIN 2 group and a VaIN 2+group.Univariate comparative analysis was performed on the two groups.Multivariate Logis-tic regression analysis was used to determine the risk factors of VaIN 2+and to construct a diagnostic model.The nomogram model was established by using R Studio software.The discrimination,calibration and clinical practical value of the model were evaluated by the area under the receiver operating characteristic(ROC)curve and cali-bration curve.Results:Univariate analysis identified that HPV type,cervical lesion grade,acetowhite change,vagi-nal lesion duration,vaginal lesion location,and cervical lesion duration as influencing factors for diagnosing VaIN 2+(P<0.1).Multivariate binary Logistic regression analysis indicated that HPV16/18 positivity,cervical lesion grade≥CIN 2,thick acetowhite change,vaginal lesion duration≥5 years,and vaginal lesion location at the upper 1/3 of the vagina were independent risk factors for diagnosing VaIN 2+(OR>1,P<0.05),while cervical lesion duration<3 years was a protective factor(OR<1,P<0.05),with acetowhite change having the greatest impact(OR4.54).A regression model was established based on the multivariate binary Logistic regression analysis,with an AUC of 0.813.A nomogram model was constructed and internally validated,yielding a consistency index(C-index)of 0.81.Patients were stratified into risk groups using the X-tile software,with higher total scores indi-cating a greater risk of developing VaIN 2+.Conclusions:The nomogram model constructed in this study can in-dividually predict the risk of VaIN 2+lesions in patients,with high accuracy and clinical practicability.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.