Objective To investigate the diagnostic value of cytokeratin 19 fragment(CYFRA21-1),squa-mous cell carcinoma antigen(SCC),neuron-specific enolase(NSE)combined with fibrinogen(FIB)in patho-logical type and lymph node metastasis of lung cancer.Methods A total of lung cancer patients admitted to Deyu Medical Maanshan General Hospital from September 2022 to March 2024 were selected as the lung canc-er group,including 14 cases of lung squamous cell carcinoma,36 cases of lung adenocarcinoma,8 cases of small cell lung cancer,39 cases of lymph node metastasis and 19 cases of no lymph node metastasis.In addition,45 patients with benign pulmonary lesions in Deyu Medical Ma'anshan General Hospital during the same period were selected as the control group.The levels of CYFRA21-1,SCC,NSE and FIB were compared between the two groups.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of CY-FRA21-1,SCC,NSE combined with FIB for pathological type and lymph node metastasis of lung cancer.Re-sults The levels of CYFRA21-1,NSE,SCC and FIB in lung cancer group were higher than those in control group(P<0.05).There were statistically significant differences in CYFRA21-1,NSE,SCC and FIB levels in patients with different pathological types of lung cancer(P<0.05).The levels of FIB and NSE levels in pa-tients with small cell lung cancer were higher than those in patients with lung squamous cell carcinoma and lung adenocarcinoma.The levels of CYFRA21-1 and SCC in patients with lung squamous cell carcinoma were higher than those in patients with lung adenocarcinoma and small cell lung cancer(P<0.05).The levels of CYFRA21-1,NSE,SCC and FIB in patients with lymph node metastasis were higher than those in patients without lymph node metastasis(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of CYFRA21-1,NSE,SCC and FIB alone and in combination were 0.795,0.620,0.672,0.757 and 0.812,re-spectively.The AUC of combined detection in the diagnosis of lung cancer,lung adenocarcinoma,lung squa-mous cell carcinoma,small cell lung cancer and lymph node metastasis were 0.812,0.837,0.786,0.922 and 0.875,respectively.Conclusion CYFRA21-1,SCC,NSE combined with FIB can improve the diagnostic value of pathological type and lymph node metastasis of lung cancer.

Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

Objective To establish an inhalation infection pneumonia model of C57BL/6J mice with highly virulent and multi-drug resistant Pseudomonas aeruginosa(PA)strain F291007,and to study the microbiological,pathological and immunological characteristics of this model.Methods The strain F291007 was isolated and identified before the bacterial suspension was administered to the mice via aerosolized intratracheal inoculation to establish the pneumonia infection model.In the course of infection,the conditions and survival of the mice were observed,and the bacterial loads,the histopathological states and the cytokine expression levels in the major organs were detected.Finally,three key cytokines were blocked to observe the survival of mice.Results The strain F291007 was isolated and identified.After lethal dose infection,all the mice died within 24 h.After sub-lethal dose infection,a large number of immune cells in the body were capable of phagocytosis and killing of invading pathogens,which was manifested as rapid clearance of bacteria in lungs and the exponential decrease of bacterial load with the passage of time.The pathological changes in lungs were most severe at 1 to 3 days but gradually recovered.After infection,interleukin-6(IL-6),IL-17A and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid and serum were significantly increased at 1 to 3 days.After blocking of these three cytokines with specific antibodies,the survival rates of infected mice decreased significantly.Conclusion A mouse model of gradually-recovered pneumonia infection caused by PA inhalation has been established,suggesting that the first one to three days are critical to immune response after infection through multiple indicators.This mouse model can be used for research on the pathogenesis,immunoregulation and treatment evaluation of highly virulent and multi-drug resistant PA inhalation pneumonia infection.

Objective To construct a non-trace deletion mutant of exlA in Pseudomonas aeruginosa strain NY8755(NY8755ΔexlA)and investigate the basic characteristics of pore-forming toxin ExlA.Methods The NY8755ΔexlA was constructed using the secondary homologous recombination method.C57BL/6J female mice ages 6 to 8 weeks were infected with NY8755 and NY8755 ΔexlA via aerosolized intratraheal inoculation respectively.Within 7 days of infection,the survival and weight changes of the mice were observed and recorded before the proinflammatory cytokines in the bronchoal-veolar lavage fluid(BALF)of the infected mice in the two groups were detected.Results The sequencing results showed that NY8755 ΔexlA was constructed.After 1×107 CFU NY8755 and NY8755 ΔexlA were infected,all the mice in the wild-type strain group died within 48 hours,while those in the mutant strain group began to die after 48 hours,and 40%of them remained alive 7 days later.The weight of surviving mice in the mutant strain group decreased but recovered gradually.After 12 hours of infection,there were more bloody exudates(redder in color)in the BALF of the wild-type strain group than in the mutant strain group,and the contents of proinflammatory cytokines interleukin-1β(IL-1β)and interleukin-17A (IL-17A)were significantly different. Conclusion Pseudomonas aeruginosa pore-forming toxin ExlA is the key pathogenic virulence factor of the exlA-positive Pseudomonas aeruginosa,which can significantly affect the survival status of mice and cause obvious inflammation in mice. Very little information is available on the action mechanisms of ExlA. In this study, The NY8755ΔexlA and the C57BL/6J mouse models infected with NY8755 and NY8755ΔexlA have been constructed that may be used for the investigation of pathogenesis of exlA-positive Pseudomonas aeruginosa.

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

Objective:To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands.Methods:Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People′s Hospital and two cases from Department of Pathology, Henan Provincial People′s Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed.Results:There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption.Conclusions:IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.

Objective: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. Materials and Methods: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18–44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23–40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20–42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Results: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361–0.812). Conclusion Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

Objective:To investigate the effect of systemic lupus erythematosus (SLE) on the status of hepatitis B virus (HBV) infection, and provide data for clarifying the relationship between autoimmunity and infection.Methods:SLE patients in the department of rheumatology and immunology of the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2019 were screened. A retrospective case-control study was carried out. SLE patients with positive hepatitis B surface antigen (HBsAg) were gender and age matched with chronic hepatitis B (CHB) in a 1∶4 ratio. Chi-square test was used to compared the positive rates of hepatitis B e antigen (HBeAg) and Paired-Samples t test or Signed rank Wilcoxon test was used to compare the HBV DNA load and HBsAg titer. Results:The positive rate of HBsAg in SLE patients was lower than the prevalence rate of HBsAg in general population in the second Chinese National Hepatitis Seroepidemiological Survey in 2006 [2.2%(27/1 227) vs 7.2%], but the positive rate of HBcAb was not obviously different from that in general population in China [33.9%(416/1 227) vs 34.1%]. Compared with matched CHB patients, the positive rate of HBeAg [37.0%(10/27) vs 58.3%(63/108), χ2=3.94, P=0.047], the HBV DNA load [0(0, 3.7) lg U/ml vs 4.8(2.2, 3.7) lg U/ml, Z=-5.37, P<0.001] and HBsAg titer [(2.0±1.5) lg U/ml vs (3.3±1.1) lg U/ml, t=-4.26, P<0.001] in SLE patients were lower. Conclusion:The HBV infection status of SLE patients is different from that of patients with chronic hepatitis B and the HBV infection is more likely to be controlled.