BACKGROUND: Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters. METHODS: A total of 112 patients with INMA who underwent preoperative DECT were retrospectively enrolled from March 2021 to January 2025. Patients were categorized into low-intermediate grade and high grade groups based on IASLC grading. The clinical characteristics and conventional CT parameters, including baseline features, biochemical markers, and serum tumor markers, were collected. DECT-derived parameters, including iodine concentration (IC), effective atomic number (eff-Z), and normalized IC (NIC), were collected and determined as NIC ratio (NICr) and fractal dimension (FD). Univariate analysis was employed to compare differences in conventional characteristics and DECT parameters between the two groups. Variables demonstrating statistical significance were subsequently incorporated into a multivariate Logistic regression analysis. A nomogram model integrating clinical data, conventional CT parameters, and DECT parameters was developed to identify independent predictors for IASLC grading of INMA. The discriminatory performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis identified smoking history [odds ratio (OR)=2.848, P=0.041], lobulation sign (OR=2.163, P=0.004), air bronchogram (OR=7.833, P=0.005), eff-Z in arterial phase (OR=4.266, P<0.001), and IC in arterial phase (OR=1.290, P=0.012) as independent and significant predictors for IASLC grading of INMA. The nomogram model constructed based on these indicators demonstrated optimal predictive performance, achieving an area under the curve (AUC) of 0.804 (95%CI: 0.725-0.883), with specificity and sensitivity of 85.3% and 65.7%, respectively. CONCLUSIONS The nomogram model based on clinical features, imaging features and spectral CT parameters have a large potential for application in the preoperative noninvasive assessment of INMA IASLC grading.
Humans ; Nomograms ; Female ; Male ; Middle Aged ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms/pathology* ; Aged ; Retrospective Studies ; Adenocarcinoma of Lung/pathology* ; Neoplasm Grading ; Adult

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective: To investigate the effect of G protein-coupled receptor 108(GPR108) gene knockout on systemic inflammation in lipopolysaccharide(LPS)-induced sepsis mice. Methods: Male C57BL/6 mice and GPR108 gene knockout mice were randomly divided into 4 groups: WT group, WT-LPS group, KO group, KO-LPS group. The physiological characteristics of mice in different groups were observed, and the morphological changes of liver and lung tissues were observed. Macrophages were extracted from bone marrow and subjected to flow cytometry to detect their M1 polarization status. The expression levels of IL-6 in liver and lung tissues, macrophages, and serum were also measured. Results: KO-LPS group mice showed significant liver and lung tissue damage, with a significantly greater number of bone marrow-derived macrophages polarizing towards M1 in the KO-LPS group compared to the WT-LPS group. Additionally, at the tissue, cellular, and serum levels, the expression of IL-6 in the KO-LPS group mice was significantly higher than that in the WT-LPS group mice(P<0.05). Conclusion During the systemic inflammatory infection induced by LPS in mice, the lack of GPR108 exacerbates the systemic inflammatory response. GPR108 has an inhibitory effect on the inflammatory response in mice with LPS-induced sepsis.

Objective To investigate the role and mechanism of urate in chronic kidney disease complicated with renal interstitial fibrosis(CKD-RIF).Methods Mice were continuously fed with a diet containing 0.2％adenine for a duration of 9 weeks to establish mice models with CKD-RIF.By the end of the 9-week experimental periods,collected blood samples from the posterior orbital venous plexus of mice to measure renal functions and serum urate concentrations prior to euthanizing the mice.Hematoxylin-eosin(HE)staining and periodic acid-Schiff staining(PAS)were used to investigate the pathological alternations in kidney tissues.Masson's trichrome staining was used to observe the extent of renal fibrosis.Urate staining was used to detect urate deposition in renal tissues.Western blot and immunohistochemistry were used to detect the expression of target molecules.Scratch tests were used to ex-amine the migration abilities of cells treated with different concentrations of uric acid.Results The kidney function analysis showed that a significant increase in the levels of serum urea nitrogen(P=0.006 4),creatinine(P=0.008 0)and urate(P=0.000 7)in the CKD-RIF mice compared with the normal control group.The results of HE staining and PAS staining showed a significance of renal tubule injury and infiltration of inflammatory cells in the model group.Masson's trichrome staining showed that a marked increase in collagen deposition in the model group.The results of urate staining showed a significant presence of urate crystals in kidney tissue of the model group when compared to the control group.Animal tissue immunoblotting and immunohistochemistry analysis showed a significant increase in the expression levels of vimentin,α-SMA and TGF-β1 in the model group in comparison to the control group.Conversely,in the model group,E-cadherin levels exhibited a dramatic reduction compared to the control group.The findings from the scratching tests showed that uric acid significantly enhanced cell migration.Western blot analysis showed a dramatic increase in the expression levels of vimentin and α-SMA,while E-cadherin exhibited significant decrease in the cells subjected to uric acid treatment.Conclusion Urate stimulates the secre-tion of TGF-β1 by renal tubule epithelial cells and induces epithelial-mesenchymal transdifferentiation,thereby ex-acerbating renal interstitial fibrosis in CKD.

Objective : To examine the role of LMO4 in the regulation of endothelial cell differentiation and angio- genesis in murine embryonic stem cells (mESC) ． Methods : Mouse Lmo4 cDNA was obtained from MEL cells by using the reverse transcription-polymerase chain reaction (RT-PCR) and subcloned into the expression vector pFG to generate the pFLG ，in which contained Flk-1 promoter to drive Lmo4 expresses in only FLK-1 + cells．The mESC were transfected with pFG or pFLG plasmids and subsequently screened with geneticin ( G418) to produce cell clones． These cell clones were named mESC /pFG and mESC /pFLG ，respectively． The mESC /pFG and mESC /pFLG were cultured in the differentiation medium for either 4 days or 10 days to generate embryoid bodies (EB) ．The 10-day embryoid bodies ( 10 d-EBs) carrying the pFG and pFLG vectors were subsequently stimulated to generate the blast-colony forming cells (BL-CFC) ，which indicated the presence of hemangioblasts．The endo- thelial cell sprouting analysis was performed by using 10 d-EBs．The expression of the interest genes was detected by using qualitative RT-PCR or Western blot analysis. Results : The pFLG expression vector was successfully con- structed through PCR identification．The mESC /pFG and mESC /pFLG cells were obtained after transfected with the pFG or pFLG vectors and selected by G418．The cells spontaneously differentiate to generate EBs，in which some green fluoresce cells were present．Western blot analysis showed that a significant increase in LMO4 expression in both 4 d-EB and 10 d-EB when compared to mESC．BL-CFC analysis showed that the 4 d-EB/ pFLG had a higher cloning efficiency ( 7. 70% ± 1. 27% ) ，comparing with that of the 4 d-EB/ pFG ( 1. 15% ± 0. 48% ) ( P = 0. 021) ．Quantitative RT-PCR results showed that the expression of Flk-1，C-kit，Tie-2 and Ve-cad genes in 10 d- EBs /pFLG increased more than 2-fold compared to 10 d-EBs /pFG．The endothelial cell sprouting analysis result showed a significant increase in the number and length of new blood vessels in 10 d-EB/ pFLG compared to 10 d- EB/ pFG (P＜0. 05) ． Conclusion Overexpression of LMO4 promotes hemangioblast differentiation from mESC， and benefits for endothelial cell differentiation and angiogenesis.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Background/Aims: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Objective:To investigate the magnetic resonance imaging (MRI) features of desmoplastic small round cell tumor (DSRCT) of the abdomen and pelvis.Method:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 8 patients with DSRCT of the abdomen and pelvis, including 3 cases admitted in Yueqing People's Hospital and 5 cases admitted in Wenzhou People's Hospital, from January 2008 to June 2022 were collected. There were 5 males and 3 females, aged (43±5)years. All patients underwent MRI plain and enhanced scanning. Observa-tion indicators: (1) imaging features of DSRCT of the abdomen and pelvis; (2) treatment and pathological examination characteristics of DSRCT of the abdomen and pelvis; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Imaging features of DSRCT of the abdomen and pelvis. ① Tumor location. Of the 8 patients, there were 6 cases with tumors located respectively at the lower edge of the liver in the right quarter costal region, the medial side of the ileocecal region in the right iliac region, the medial side of the caecum in the right iliac region, the gastro-pancreatic space in the left quarter costal region, the mesenteric space in the left iliac region and the right side of pelvic bladder, and 2 cases with tumors located at retroperitoneal space of left quarter rib region. ② Tumor size. There were 13 lesions in the 8 patients, and the maximum diameter of tumor was 9.1 (range, 3.5?20.0)cm. Of the 8 patients, there were 5 cases with single tumor and 3 cases with multiple tumors. ③ Tumor shape and boundary. Of the 8 patients, there were 4 cases with tumor in expansive growth and 4 cases with tumor in invasive growth. There were 5 cases with tumor of intratumoral necrosis and cystic degene-ration, 4 cases with tumor of intratumoral hemorrhage, 4 cases with tumor of intratumoral spot calcification, 3 cases with tumor of peritumoral tissue exudation. One patient may combined with multiple imaging manifestations. ④ Imaging characteristics of MRI plain scanning. Of the 8 patients, there were 4 cases with tumor of homogeneous hypointensity signal and 4 cases with tumor of hypointensity mixed with speckled hyperintensity (with hemorrhage) in T1 weighted imaging of MRI plain scanning. There were 3 cases with tumor of homogeneous hyperintensity and 5 cases with tumor of high signal at the edge, patchy and spot-shaped in the center in T2 weighted imaging of MRI plain scanning. There were 5 cases with tumor of high, equal and low confounding signals and 3 cases with tumor of high and low signals in T2 weighted imaging fat suppression sequence of MRI plain scanning. There were 3 cases with tumor of uniform high signals and 5 cases with tumor of high, equal and low mixed signals in diffusion weighted imaging of MRI plain scanning. ⑤ Imaging characteristics of MRI enhanced scanning. All 8 patients had tumor of heterogeneous enhancement in MRI enhanced scanning, including 2 cases with significant enhancement in arterial phase, continuous enhancement in portal phase, slightly reduced enhancement in delayed phase, 4 cases with moderate enhancement in arterial phase, continuous enhancement in portal phase, slowly exited enhancement in delayed phase, 2 cases with mild enhancement in arterial phase, continuous enhancement in portal phase, slowly exited enhancement in delayed phase. Of the 8 patients, there were 3 cases with tumor of annular enhancement with intratumoral strip or grid signals and 3 cases with tumor of peritumoral blood vessels increased and thickened signals. ⑥ Tumor invasion and metastasis. Of the 8 patients, there were 4 cases with tumor invaded bowel, 2 cases with tumor invaded surrounding tissues, 1 case with tumor invaded left kidney, spleen and pancreatic tail, 1 case with tumor invaded distal of left ureter. There were 5 cases with abdominal, retroperitoneal and inguinal lymph nodes enlargement, 4 cases with multiple nodular thickening of peritoneum and ascites, 2 cases with tumor liver and lung metastasis and 1 case with tumor rib, femur and sacrum metastasis. One patient may combined with multiple tumor metastasis. (2) Treatment and patholo-gical examination characteristics of DSRCT of the abdomen and pelvis. Of the 8 patients, 3 patients underwent complete resection as clear tumor boundary, 3 patients underwent tumor partial resection as tight adhesion between tumor and surrounding blood vessels, 2 cases underwent tumor tissue pathological examination as extensive metastasis of peritoneum, omentum, mesentery and surrounding intestine. All 8 patients were diagnosed as DSRCT by microscopic examination, electron microscopic examination, immunohistochemical staining and cytogenetic examination. (3) Follow-up. All 8 patients underwent postoperative follow-up and died during the follow-up.Conclusion:MRI features of abdominal and pelvic DSRCT include single or multiple lobulated masses with unclear boundaries, invading the omentum, mesentery, peritoneum and adjacent tissues in most cases, mixed signals and heterogeneous mild to moderate enhancement in enhanced scanning.

The diagnostic technology of acute stroke by microwave imaging has the advantages of being non-ionizing, fast, small, and low-cost. Therefore, this technology is expected to become an auxiliary or alternative means to CT and MRI technology. As the signal transmitting and receiving device of the microwave imaging system, the antenna has an important influence on the performance of the imaging system. At present, there are many antennas with different performances used in imaging systems, but there is a lack of clear evaluation criteria for them. In this paper, several typical antennas were introduced, their advantages and disadvantages from the perspective of bandwidth and near-field were analyzed, and the common requirements of imaging systems for antennas and the performance indicators of various types of imaging systems were summarized. Moreover, the development trend of antenna technology for microwave imaging was pointed out to provide a reference for the study of stroke microwave imaging technology.

Objective:To explore the imaging features of hyperostosis frontalis interna (HFI).Methods:One hundred patients with clinically diagnosed HFI were enrolled from Department of Radiology, Yueqing People's Hospital and Department of Imaging, Wenzhou People's Hospital from January 2011 to December 2022. MRI alone was performed in 45 patients; MRI+DR was performed in 14, and MRI+CT was performed in 41. The imaging features of these patients were analyzed retrospectively.Results:In these 100 patients, 20 were with external hyperplasia, 51 with internal hyperplasia, and 29 with intermediate hyperplasia. External hyperplasia manifested as proliferating towards the diploe, enjoying clear boundary, uniform high signals of the hyperplastic inner plate and diploe on T1WI and T2WI, and high density of the hyperplastic inner plate and diploe on CT and DR. Internal hyperplasia manifested as proliferating towards the cranial cavity, enjoying wavy or nodular inner edges, non-uniform low signals of hyperplastic inner plate on T1WI and T2WI, and high density of the hyperplastic inner plate on CT and DR. Intermediate hyperplasia manifested as proliferating simultaneously towards the cranial cavity and diploe, enjoying thin and blurred diploe, uniform or non-uniform high signals of the hyperplastic inner plate and diploe on T1WI and T2WI, and non-uniform high density of the hyperplastic inner plate and diploe on CT and DR. Compressed and displaced brain parenchyma, reduced anterior cranial fossa volume, and narrowed subarachnoid space were noted in these 100 patients, including 47 patients with obvious frontal lobe brain tissue compression (depth of 3.0-17 mm, averaged [8.6±5.9] mm), 35 with lacunar cerebral infarction, 33 with subcortical arteriosclerotic encephalopathy, and 32 with varied degrees of cerebral atrophy.Conclusion:HFI is characterized by thickening and hardening of the bilateral frontal bone inner plates, with wavy, nodular or spindle-shaped inner edges, compressed brain tissues, and reduced anterior cranial fossa; these imaging features can help the definite diagnosis of HFI.