OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective To explore the application of artificial intelligence (AI) in the standardized training of thoracic surgery residents, specifically in enhancing clinical skills and anatomical understanding through AI-assisted lung nodule identification and lung segment anatomy teaching. Methods Thoracic surgery residents undergoing standardized training at Peking Union Medical College Hospital from September 2023 to September 2024 were selected. They were randomly assigned to a trial group and a control group using a random number table. The trial group used AI-assisted three-dimensional reconstruction technology for lung nodule identification, while the control group used conventional chest CT images. After basic teaching and self-practice, the ability to identify lung nodules on the same patient CT images was evaluated, and feedback was collected through questionnaires. Results A total of 72 residents participated in the study, including 30 (41.7%) males and 42 (58.3%) females, with an average age of (24.0±3.0) years. The trial group showed significantly better overall diagnostic accuracy for lung nodules (91.9% vs. 73.3%) and lung segment identification (100.0% vs. 83.70%) compared to the control group, and the reading time was significantly shorter [ (118.5±10.5) s vs. (332.1±20.2) s, P<0.01]. Questionnaire results indicated that 94.4% of the residents had a positive attitude toward AI technology, and 91.7% believed that it improved diagnostic accuracy. Conclusion AI-assisted teaching significantly improves thoracic surgery residents’ ability to read images and clinical thinking, providing a new direction for the reform of standardized training.

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Objective To investigate the clinical features and maternal and fetal outcomes of acute pancreatitis in pregnancy(APIP)and the risk factors for disease aggravation,and to establish a predictive model.Methods A retrospective analysis was performed for 52 APIP patients who were admitted to Affiliated Hospital of Zunyi Medical University from January 2017 to December 2022,and according to disease severity,they were divided into mild acute pancreatitis(MAP)group with 32 patients,moderate-severe acute pancreatitis(MSAP)group with 8 patients,and severe acute pancreatitis(SAP)group with 12 patients.The logistic regression analysis was performed for the clinical data of each group,and the receiver operating characteristic(ROC)curves were plotted to assess the value of risk factors in predicting the severity of APIP.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparision between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups,and the Wilcoxon rank-sum test was used for further comparision between two groups;the chi-square test was used for comparison of categorical data between groups.Results Of all patients in terms of etiology,26(50%)had hyperlipidemic pancreatitis,20(38.4%)had biliary pancreatitis,and 6(11.5%)had idiopathic pancreatitis.In terms of gestational week,1 patient(1.9%)was in early pregnancy,25(48.1%)were in mid-pregnancy,and 26(50.0%)were in late pregnancy.A total of 10 patients(19.2%)had acute respiratory distress syndrome(ARDS),among whom 9(90%)required respiratory support.There were significant differences between the patients with different severities of APIP in aspartate aminotransferase,alanine aminotransferase,blood urea nitrogen,blood glucose,C-reactive protein(CRP),international normalized ratio(INR),pneumonia,ARDS,sepsis,hepatic insufficiency,and coagulation dysfunction(all P<0.05).The univariate analysis showed that the severity of APIP was associated with blood glucose,blood urea nitrogen,CRP,and pneumonia(all P<0.05),and pneumonia was a risk factor for the aggravation of APIP(odds ratio=18.938,95%confidence interval:1.020—351.747,P=0.048).CRP,blood glucose,blood urea nitrogen,and INR used in combination had a larger area under the ROC curve than each index used alone(0.954 vs 0.778/0.796/0.721/0.801).Conclusion Pneumonia is a risk factor for the aggravation of APIP,and the combination of CRP,blood glucose,blood urea nitrogen,and INR can be used to predict the severity of APIP.

Objective:To assess the predictive value of a combined multiclassification model for computed tomography(CT)in the patholo-gical analysis of ground-glass nodules(GGN).Methods:Pulmonary GGN lesions that were pathologically confirmed as invasive adenocar-cinoma(IAC),minimally invasive adenocarcinoma(MIA),adenocarcinoma in situ(AIS),and preinvasive lesions(PILs),were collected from pa-tients who were treated at The First Affiliated Hospital of Xinxiang Medical University between February 2019 and March 2023.A total of 324 nodules were retrospectively collected from 285 patients,and divided into three groups:infiltrating IAC,MIA,and PILs.Radiomics and clinical-CT features were selected through recursive feature elimination and univariate Logistic regression.Seven models were constructed using Logistic regression(LR),support vector machine(SVM),random forest(RF),and integrative learning(stacking).Results:The hybrid model combining clinical-CT-radiomics features and an integrative strategy showed superior predictive performance,with an accuracy of 0.791,precision of 0.788,specificity of 0.857,recall of 0.790,and F1-Score of 0.789.Conclusions:The multiclassification joint model based on CT-radiomics is effective in predicting pathological classification of pulmonary GGNs.This model aids in accurate imaging diagnosis and can provide a basis for optimizing treatment plans.

Objective To explore the application value of multidetector computed tomography(MDCT),computed tomography cholangiography(CTC)and computed tomography angiography(CTA)reconstruction technology in the diagnosis and classification and the evaluation of the efficacy of biliary drainage in advanced hilar cholangiocarcinoma(HCCA).Methods A total of 44 patients of inoperable advanced HCCA were collected.Conventional CT plain scan and enhanced multi-phase scan were performed before treat-ment.Minimum intensity projection(MinIP)combined with curve planar reformation(CPR)was used to perform CTC.CTA of the portal vein,hepatic artery and hepatic vein were performed by maximum intensity projection(MIP),volume rendering(VR)or CPR,respectively.CT was reexamined after biliary drainage treatment.The study included the comparison between reconstruction technology of CTC and CTA and conventional CT scanning technology,CTC in the classification and diagnosis of HCCA,CTA in the evaluation of vascular invasion,and the evaluation of the effect of jaundice drainage by biliary imaging before and after biliary drain-age treatment.Results All HCCA cases obtained clear location diagnosis,including 39 cases of Bismuth-Corlette type Ⅳ and 5 cases of type Ⅲ.There were 40 cases of hepatic vascular involvement,including 15 cases of bilateral portal vein invasion by tumor,12 cases of portal vein constriction,8 cases of portal vein tumor thrombosis,4 cases of bilateral hepatic arteries involvement,and 1 case of hepatic vein involvement.CTC and CTA could better display a full view of the bile duct and blood vessel than conventional CT scanning ima-ges,and provided more accurate analysis of tumor classification and degree of vascular invasion.Before treatment,CT showed severe dila-tion of bile duct in 21 cases and moderate dilation in 20 cases,severe dilation of the intrahepatic bile duct in the left lobe but mild dilation of the intrahepatic bile duct in the right lobe in 3 cases.After drainage treatment,the contraction rate of intrahepatic bile duct dilation was＜25％in 4 cases,25％to 49％in 13 cases,50％to 74％in 18 cases,and ≥75％in 9 cases.The bile duct contraction rate was positively correlated with the decrease in total bilirubin(TBIL).Conclusion MDCT,CTC and CT A reconstruction technology can well complete the diagnosis of advanced HCCA,Bismuth-Corlette typing,and vascular evaluation.Observing the contraction rate of the intrahepatic bile duct after biliary drainage treatment can evaluate the efficacy of jaundice drainage.

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a new respiratory infectious disease.Patients with chronic kidney disease are at high risk of SARS-CoV-2 infection.Once they develop SARS-CoV-2 infection,the rate of progression to severe illness or even death is much higher than that of the general population.Nirmatrelvir/ritonavir significantly reduce the risk of severe illness and death in patients infected with SARS-CoV-2.In this paper,the dosing regimen and drug interaction of nirmatrelvir/ritonavir in patients with different stages of chronic kidney disease complicated with SARS-CoV-2 infection were reviewed to provide a reference for clinical rational medication for patients with chronic kidney disease.

Abstract: Objective　To analyze epidemiological characteristics of influenza in Nanning from 2013 to 2022, to provide a reference for the prevention and control of influenza. Methods The data of influenza incidence and etiology surveillance results of the influenza virus in Nanning from 2013 to 2022 were collected to build a database. Data statistical analysis was performed through SPSS 21.0 and Joinpoint software to explore the epidemic trend and epidemic characteristics of the influenza virus in Nanning, and the seasonal index method was used to analyze the epidemic seasons. Results The reported incidence of influenza in Nanning showed an overall upward trend from 2013 to 2022, with an annual percent change (APC) of 47.63% (P<0.05), and an average annual incidence rate of 84.47/105 (ranging from 6.65/105 to 302.55/105). The peak months for influenza in Nanning were January, June, and December, with the seasonal indices of influenza all exceeding 100%, and the proportions of reported cases was 12.69%, 29.41%, and 25.97%, respectively. Both male and female incidence rates showed an upward trend without significant difference (P=0.66). The male-to-female case ratio was 1.24∶1, with the highest case distribution in the 5-<10 years age group, accounting for 31.17%, mainly among students, scattered children, and preschoolers. Xixiangtang District reported the largest influenza cases (21.12%), and Xingning District had the highest annual incidence (214.72/105). Influenza outbreaks mainly occurred in schools and kindergartens, accounting for 97.84%; primary schools accounted for 63.07% of the total. From 2013 to 2022, the dominant strains of influenza viruses alternated in Nanning, with a higher proportion of influenza A (H1N1) and (H3N2) viruses from Jan. 2013 to Mar. 2019. The dominant strains from April 2019 to Dec. 2022 were influenza A (H3N2) and B (Victoria) lineage. Conclusions The intensity of the influenza epidemic in Nanning City showed an increasing trend from 2013 to 2022, with obvious seasonality. The dominant subtypes of influenza viruses varied each year. The main affected groups were students and children, and the outbreaks mainly occurred in schools. Therefore, it is necessary to strengthen the prevention and control of influenza in schools, and the timely detection and handling of outbreaks.