ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

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 summarize and analyze the clinical characteristics of systemic lupus erythematosus (SLE) combined with ischaemic stroke and the factors associated with poor prognosis.Methods:A total of 50 patients with SLE combined with ischaemic stroke in the First Affiliated Hospital of Xi′an Jiaotong University from January 2014 to June 2024 were included in the study, the clinical data of the patients were retrospectively collected and summarized, the Shapiro-Wilk test was used to assess the normality of data, and the factors related to poor prognosis were analyzed by logistic regression analyses.Results:Fifty patients with SLE combined with ischaemic stroke had a mean age of (47.1±15.5)years, 80.0%(40/50) were female, the duration of SLE was (5.6±6.3)years, the mean SLEDAI-2K score was (14.3±4.1), the rate of anticardiolipin antibody positivity was 30.0%(15/50), and the rate of β 2-glycoprotein Ⅰ antibody positivity was 28.0%(14/50). The most common clinical manifestations of stroke were impaired limb movement (34.0%) (17/50), cerebral infarction mainly in the cerebral hemisphere (82.0%)(41/50), combined with cerebral haemorrhage in 6.0%(3/50), cerebral leukoencephalopathy in 26.0%(13/50), and cerebral atrophy in 24.0%(12/50). In terms of treatment, the most used immunosuppressant was cyclophosphamide (34.0%, 17/50), 64.0%(32/50) of patients received aspirin, 32.0%(16/50) received clopidogrel and 14.0%(7/50) received anticoagulation. Four deaths and 12 cases of severe disability were found in 50 patients at follow-up, and SLEDAI-2000 scores were positively correlated with the above poor prognosis using univariate [ OR(95% CI)=1.407(1.123,1.764), P=0.003] and multivariate [ OR(95% CI)=1.388(1.097, 1.756), P=0.006] regression analyses. Conclusion:Patients with SLE combined with ischaemic stroke had high disease activity in SLE, and SLEDAI-2000 scores were positively associated with poor prognosis of death and severe disability.

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Purpose To investigate the evaluation value of multimodal MRI in the outcome of traumatic brain injury(TBI)in rats.Materials and Methods A total of 30 TBI rat models were established,randomly divided into an untreated TBI group and a TBI treated group(hyperbaric oxygen)with 15 rats each.The Sham group with 15 rats was used as a healthy control,and the brain injury status of the rats was evaluated at 1 d,3 d,7 d,14 d and 28 d of modeling.Multimodal MRI was performed in parallel,and coronary T2WI,diffusion weighted imaging,diffusion kurtosis imaging and diffusion tensor imaging sequences were routinely scanned.The correlation between rat neurological function scores and various sequence parameters were analyzed,as well as multimodal MRI and the outcome of brain injury after TBI treatment in rats.Results The neurological function score and average kurtosis of the TBI treatment group were lower than those of the TBI untreated group(P<0.05).The apparent diffusion coefficient and anisotropy score of the TBI treatment group were higher than those of the TBI untreated group(P<0.05).The diffusion weighted imaging parameter apparent diffusion coefficient value and diffusion tensor imaging parameter fraction anisotropy value were negatively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=-0.675,-0.611,P<0.05),while the diffusion kurtosis imaging parameter mean kurtosis value was positively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=0.623,P<0.05).Conclusion Multimodal MRI can effectively evaluate the brain injury status of TBI rats and provide valuable information for dynamic evaluation after hyperbaric oxygen therapy for TBI,with high evaluation value in treatment outcomes.

Objective:To investigate the expression pattern of pan-TRK protein in colorectal cancers with NTRK gene fusion and mismatch repair deficient (dMMR) and to analyze its molecular pathological characteristics.Methods:A total of 117 dMMR colorectal cancers diagnosed in the Department of Pathology of Henan Provincial People′s Hospital, Zhengzhou, China from 2020 to 2023 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA/RNA-based next-generation sequencing (NGS) were used to detect pan-TRK protein expression and fusion partner genes in tumors, and to further explore the correlation between pan-TRK staining patterns and partner genes.Results:IHC and FISH were performed successfully in formalin-fixed paraffin-embedded tissues from 117 dMMR colorectal cancer patients. There were 15 (15/117, 12.8%) cases with positive pan-TRK, including 6 cases with strong staining in tumor cell membrane and cytoplasm, 2 cases with weakly granular staining in tumor cytoplasm, 2 cases with moderate dot-like staining in near 5% tumor cell nuclei, 1 case with moderately to strongly granular staining in the cytoplasm and membrane of tumor cells, 1 case with moderately to weakly granular staining in about 60% of the tumor cells, 1 case with strongly staining in about 1% of the tumor cells, 1 case with moderately to strongly staining in about 3% of the tumor cells and 1 case with diffuse, moderate para-nuclear dot-like and weakly perinuclear granular staining. NTRK1 gene disruption was detected in 6 cases (6/117, 5.1%) and consistent with diffusely strong expression of pan-TRK. Based on DNA/RNA NGS, it was further confirmed that the 6 cases with NTRK1 gene disruption all carried TPM3-NTRK1 fusion gene, and all had high microsatellite instability and high tumor mutation burden. No KRAS, NRAS, BRAF V600E or TP53 gene mutations were detected. Four patients carried frame shift mutations in RNF43. Other molecular changes included 3 cases with ROS1 gene mutation, 2 cases with BRAC, ALK, and EGFR gene mutations, 2 cases with ATM gene mutation, and 2 cases with KIT gene mutation. These were missense/frame shift mutations that were associated with no clinical significance. The nine pan-TRK-positive cases without NTRK gene fusion detected with DNA-based NGS were further confirmed with RNA-based NGS, and no NTRK gene fusion was found. The sensitivity and specificity of NTRK gene fusion detected using IHC were 100.0% and 92.5%, respectively. The sensitivity and specificity of diffusely strong membranous/cytoplasmic staining were both 100.0%.Conclusions:Pan-TRK protein has various expression patterns in dMMR colorectal cancer. Its diffusely strong expression is highly suggestive of NTRK1 gene fusion. TPM3-NTRK1 gene fusion is a common form of NTRK gene fusion in dMMR colorectal cancer.

Objective:To investigate the expression pattern of pan-TRK protein in colorectal cancers with NTRK gene fusion and mismatch repair deficient (dMMR) and to analyze its molecular pathological characteristics.Methods:A total of 117 dMMR colorectal cancers diagnosed in the Department of Pathology of Henan Provincial People′s Hospital, Zhengzhou, China from 2020 to 2023 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA/RNA-based next-generation sequencing (NGS) were used to detect pan-TRK protein expression and fusion partner genes in tumors, and to further explore the correlation between pan-TRK staining patterns and partner genes.Results:IHC and FISH were performed successfully in formalin-fixed paraffin-embedded tissues from 117 dMMR colorectal cancer patients. There were 15 (15/117, 12.8%) cases with positive pan-TRK, including 6 cases with strong staining in tumor cell membrane and cytoplasm, 2 cases with weakly granular staining in tumor cytoplasm, 2 cases with moderate dot-like staining in near 5% tumor cell nuclei, 1 case with moderately to strongly granular staining in the cytoplasm and membrane of tumor cells, 1 case with moderately to weakly granular staining in about 60% of the tumor cells, 1 case with strongly staining in about 1% of the tumor cells, 1 case with moderately to strongly staining in about 3% of the tumor cells and 1 case with diffuse, moderate para-nuclear dot-like and weakly perinuclear granular staining. NTRK1 gene disruption was detected in 6 cases (6/117, 5.1%) and consistent with diffusely strong expression of pan-TRK. Based on DNA/RNA NGS, it was further confirmed that the 6 cases with NTRK1 gene disruption all carried TPM3-NTRK1 fusion gene, and all had high microsatellite instability and high tumor mutation burden. No KRAS, NRAS, BRAF V600E or TP53 gene mutations were detected. Four patients carried frame shift mutations in RNF43. Other molecular changes included 3 cases with ROS1 gene mutation, 2 cases with BRAC, ALK, and EGFR gene mutations, 2 cases with ATM gene mutation, and 2 cases with KIT gene mutation. These were missense/frame shift mutations that were associated with no clinical significance. The nine pan-TRK-positive cases without NTRK gene fusion detected with DNA-based NGS were further confirmed with RNA-based NGS, and no NTRK gene fusion was found. The sensitivity and specificity of NTRK gene fusion detected using IHC were 100.0% and 92.5%, respectively. The sensitivity and specificity of diffusely strong membranous/cytoplasmic staining were both 100.0%.Conclusions:Pan-TRK protein has various expression patterns in dMMR colorectal cancer. Its diffusely strong expression is highly suggestive of NTRK1 gene fusion. TPM3-NTRK1 gene fusion is a common form of NTRK gene fusion in dMMR colorectal cancer.

Purpose To investigate the evaluation value of multimodal MRI in the outcome of traumatic brain injury(TBI)in rats.Materials and Methods A total of 30 TBI rat models were established,randomly divided into an untreated TBI group and a TBI treated group(hyperbaric oxygen)with 15 rats each.The Sham group with 15 rats was used as a healthy control,and the brain injury status of the rats was evaluated at 1 d,3 d,7 d,14 d and 28 d of modeling.Multimodal MRI was performed in parallel,and coronary T2WI,diffusion weighted imaging,diffusion kurtosis imaging and diffusion tensor imaging sequences were routinely scanned.The correlation between rat neurological function scores and various sequence parameters were analyzed,as well as multimodal MRI and the outcome of brain injury after TBI treatment in rats.Results The neurological function score and average kurtosis of the TBI treatment group were lower than those of the TBI untreated group(P<0.05).The apparent diffusion coefficient and anisotropy score of the TBI treatment group were higher than those of the TBI untreated group(P<0.05).The diffusion weighted imaging parameter apparent diffusion coefficient value and diffusion tensor imaging parameter fraction anisotropy value were negatively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=-0.675,-0.611,P<0.05),while the diffusion kurtosis imaging parameter mean kurtosis value was positively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=0.623,P<0.05).Conclusion Multimodal MRI can effectively evaluate the brain injury status of TBI rats and provide valuable information for dynamic evaluation after hyperbaric oxygen therapy for TBI,with high evaluation value in treatment outcomes.

Objective:To summarize and analyze the clinical characteristics of systemic lupus erythematosus (SLE) combined with ischaemic stroke and the factors associated with poor prognosis.Methods:A total of 50 patients with SLE combined with ischaemic stroke in the First Affiliated Hospital of Xi′an Jiaotong University from January 2014 to June 2024 were included in the study, the clinical data of the patients were retrospectively collected and summarized, the Shapiro-Wilk test was used to assess the normality of data, and the factors related to poor prognosis were analyzed by logistic regression analyses.Results:Fifty patients with SLE combined with ischaemic stroke had a mean age of (47.1±15.5)years, 80.0%(40/50) were female, the duration of SLE was (5.6±6.3)years, the mean SLEDAI-2K score was (14.3±4.1), the rate of anticardiolipin antibody positivity was 30.0%(15/50), and the rate of β 2-glycoprotein Ⅰ antibody positivity was 28.0%(14/50). The most common clinical manifestations of stroke were impaired limb movement (34.0%) (17/50), cerebral infarction mainly in the cerebral hemisphere (82.0%)(41/50), combined with cerebral haemorrhage in 6.0%(3/50), cerebral leukoencephalopathy in 26.0%(13/50), and cerebral atrophy in 24.0%(12/50). In terms of treatment, the most used immunosuppressant was cyclophosphamide (34.0%, 17/50), 64.0%(32/50) of patients received aspirin, 32.0%(16/50) received clopidogrel and 14.0%(7/50) received anticoagulation. Four deaths and 12 cases of severe disability were found in 50 patients at follow-up, and SLEDAI-2000 scores were positively correlated with the above poor prognosis using univariate [ OR(95% CI)=1.407(1.123,1.764), P=0.003] and multivariate [ OR(95% CI)=1.388(1.097, 1.756), P=0.006] regression analyses. Conclusion:Patients with SLE combined with ischaemic stroke had high disease activity in SLE, and SLEDAI-2000 scores were positively associated with poor prognosis of death and severe disability.

Objective:To analyze the bone turnover markers in systemic lupus erythematosus (SLE) patients with different disease activity and the risk factors of osteoporosis.Methods:In this retrospective study, a total of 417 SLE inpatients were enrolled from the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi′an Jiaotong University, from March 2019 to June 2020. According to SLEDAI score, the patients were divided into 3 groups: 281 patients disease with inactive disease group; 99 patients with mild active disease group; and 37 patients with moderate/severe active disease. ANOVA test was used to compare the differences in serum bone turnover markers (PTH, NOST, VITDT, β-crossl, TP1NP, Ca and P) and bone density (Spine L 1~4 and left femur) among the three groups, and Tukey's method was used for the two groups comparison. Logistic regression analysis was used to investigate the risk factors of osteoporosis. Results:Serum VITDT, β-crossl and Ca levels were significantly different among the 3 groups ( F=11.66, P<0.001; F=7.22, P<0.001; F=29.38, P<0.001). Compared with patients in the inactive group, patients with both the mild disease group (VITDT: t=3.94, P<0.001; Ca: t=5.10, P<0.001) and the moderate/severe disease group (VITDT: t=3.33, P<0.001; Ca: t=7.19, P<0.001) had lower VITDT levels [(20.3±9.7) ng/ml vs. (15.9±9.3) ng/ml vs. (14.8±7.4) ng/ml] and serum Ca levels [(2.19±0.15)mmol/L vs. (2.09±0.21)mmol/L vs. (2.00±0.16)mmol/L]. Moreover, the moderate/severe disease group patients had much lower serum Ca levels ( t=2.36, P<0.05), compared with patients with the mild disease group. Compared with the patients with inactive group, both the mild activey group ( t=3.06, P<0.01) and the moderate/severe activie group ( t=2.99, P<0.01) patients had higher serum β-crossl levels [(419±316) pg/ml vs. (543±424) pg/ml vs. (586±343) pg/ml]. Compared with patients with the inactive disease group both patienes with the mild active group and the moderate/severe disease group patients had significantly decreased spine BMD ( t=2.75, P<0.01; t=2.71, P<0.01), Z-score ( t=5.65, P<0.001; t=4.70, P<0.001), T-score ( t=3.02, P<0.01; t=3.37, P<0.001), whereas, no difference was found between the mild disease group and moderate/severe disease group. Compared with the inactive group patients, both the mild active group and moderate/severe disease group patients had lower left femur BMD levels ( t=2.83, P<0.001; t=2.65, P<0.001) and T-score ( t=2.24, P<0.05; t=1.977, P<0.05) and no difference was found between the mild disease group and the moderate/severe disease group. Logistic regression analysis showed that age [ HR (95% CI)=1.080 (1.052, 1.109), P<0.001], BMI [ HR (95% CI)=0.801 (0.704, 0.911), P<0.001], SLEDAI score [ HR (95% CI)=1.047 (1.025, 1.076), P<0.05] and cumulative glucocorticoids dose [1.046 (1.006, 1.087), P<0.05] were associated with osteoporosis of SLE patients. Conclusion:Abnormal bone metabolism and decreased bone density are associated with SLE disease activity in SLE patients, especially in those with advanced age, low BMI and receiving high cumulative dose of glucocorticoids. Osteoporosis should be proactively prevented in the SLE patients.