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 analyze the CT and MRI manifestations of hepatic angiomyolipoma (HAML) to improve the diagnostic accuracy of HAML.Methods:A retrospective analysis was conducted on the clinical data of 46 cases of HAML confirmed by tumor surgery or biopsy in Yueqing People's Hospital of Zhejiang and Rui'an People's Hospital of Zhejiang from November 2015 to June 2024. Among them, there were 20 males and 26 females, with an average age of (40±18) years. The CT and MRI manifestations of the patients were recorded, and the tumor location, size, shape, boundary, CT density, T 1-weighted imaging, T 2-weighted imaging, diffusion-weighted imaging (DWI), fat suppression sequence, and inverse phase signal were observed. Results:29 cases underwent plain CT scan combined with enhanced scan. Among them, 4 cases (13.8%) had a round shape, 22 cases (47.8%) had a nearly round shape, and 3 cases (10.3%) had an irregular shape. 26 cases (89.7%) had clear boundaries, and 3 cases (10.3%) had unclear boundaries. 5 cases (17.2%) had uniform density, and 24 cases (82.8%) had non-uniform density. The CT value of the tumor was (32±6.8) Hu. 25 cases (86.2%) contained fat tissue within the tumor. Among them, 13 cases (44.8%) were mixed type. After enhancement, the fat tissue and necrotic cystic changes did not enhance, and the soft tissue components showed varying degrees of enhancement in the arterial phase. Among them, 6 cases continued to enhance in the portal venous phase and delayed phase, showing " fast in and slow out" , and 7 cases showed decreased enhancement in the portal venous phase and delayed phase, showing " fast in and fast out" . 17 cases underwent plain MRI scan combined with enhanced scan. Among them, 12 cases were mixed type. On T 2-weighted imaging with fat suppression, it was a mixed high signal, on T 1-weighted imaging, it was an isointense/low signal or mixed low signal, and on DWI, it was a high signal, with partial signal reduction on the inverse phase. 9 cases of tumor septation showed isointense signals on T 1-weighted imaging, 7 cases showed isointense signals on T 2-weighted imaging, and 2 cases showed high signals on T 2-weighted imaging. After enhancement, the mass showed heterogeneous enhancement, with 7 cases showing " fast in and fast out" and 5 cases showing " fast in and slow out" . Conclusion:Plain CT scan shows that HAML is round or nearly round, with non-uniform low density or uniform isodensity. Plain MRI scan shows isointense or slightly high signal on T 2-weighted imaging, low signal on T 1-weighted imaging, and high signal on T 2-weighted imaging with fat suppression. After enhancement, there is significant or mild to moderate enhancement in the arterial phase, with " fast in and fast out" or " fast in and slow out" as the characteristics.

Objective : To construct a human keratinocyte-forming cell line(HaCaT) with stable knockout of the G protein-coupled receptor 107(GPR107) gene, and to preliminarily investigate the effect of GPR107 deletion on the biological behaviour of HaCaT cells. Methods : Using CRISPR/Cas9 gene editing technology, HaCaT cells with knockout ofGPR107gene were constructed and monoclonal cells with GPR107 deletion were obtained by limited dilution method. Genomic DNA was amplified using Western blot and PCR and sequenced to validate the single-cell clones with knockdown of GPR107. The cell cycle changes were detected by flow cytometry; cell proliferation was detected by CCK-8; apoptosis was detected by flow cytometry; changes in cell differentiation markers were detected by Western blot; cell migration ability was analyzed by cell scratch assay and other methods. Results : LentiCas9-Blast and plenti-guide-RNA-GPR107 plasmids were successfully transfected into HaCaT cells, 21 monoclonal cell lines were obtained by limited dilution, and Western blot showed that the GPR107 expression was significantly reduced in 8 of them; PCR sequencing of the cellular genome was used, which resulted in the obtainment of C4 and 2D8GPR107-/-HaCaT monoclonal cell lines. CCK-8 assay and flow cytometry assay showed thatGPR107gene deletion resulted in G0G1phase block, significantly weakened proliferation ability and increased apoptosis level of HaCaT cells. Western blot found that the differentiation of HaCaT cells accelerated after knockdown ofGPR107. Additionally the results of the cell scratch assay indicated that the migration ability of HaCaT cells was enhanced after knockdown ofGPR107. The results showed that the migration ability of HaCaT cells was enhanced after knockdown ofGPR107. Conclusion HaCaT cell line withGPR107gene deletion is successfully constructed, GPR107 deletion blocks the G0G1phase of HaCaT cells, which inhibiting the proliferation of HaCaT cells and promoted apoptosis, and it was found that the differentiation and migration of HaCaT cells were enhanced after knocking downGPR107.

Objective To investigate the application value of 320-slice wide-detector multi-phase left at-rial appendage computed tomography angiography(LAA-CTA)with pulmonary artery(PA)monitoring in the preoperative evaluation of left atrial appendage closure.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent LAA-CTA before left atrial appendage closure.Among them,47 patients underwent single-phase enhanced scanning with superior vena cava(SVC)monitoring(con-trol group),and 63 patients underwent multi-phase enhanced scanning with pulmonary artery monitoring(study group).The differences in imaging effects of the left atrial appendage under different monitoring points and phase imaging methods were compared,as well as the accuracy of comparing with the diagnostic results of transesophageal ultrasound(TEE),and the differences in the presentation of thrombus,perithrombus,and hypoperfusion areas in the left atrial appendage.Results The study group could comprehensively display the multi-phase CT value changes of different components(thrombus,peri-thrombotic viscosity,normal blood)within the left atrial appendage cavity,and its evaluation of lesion size and progression was superior to that of the control group.Using TEE as the gold standard,the study group demonstrated better diagnostic ac-curacy for different components and normal regions within the left atrial appendage cavity compared to the control group(P<0.001).Additionally,the study group improved the detection rate of peri-thrombotic vis-cosity,clearly delineated thrombus boundaries,and enhanced diagnostic accuracy(P<0.001).Conclusion Multi-phase LAA-CTA with pulmonary artery monitoring can effectively evaluate the morphological dimensions,thrombus,and peri-thrombotic CT manifestations of the left atrial appendage.It is simple to operate,with an accuracy rate close to the gold standard,providing reliable imaging evidence for preoperative evaluation of left atrial appendage closure.

Objective To explore the value of diffusion-weighted magnetic resonance imaging(MRI-DWI)and arterial spin labeling magnetic resonance imaging(ASL)in evaluating the efficacy of chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma.Methods A total of 103 patients with locally advanced nasopharyngeal carcinoma who received synchronous radiotherapy and chemotherapy in Qinghai Armed Police Corps Hospital from January 2021 to December 2023 were selected as research subjects.The apparent diffusion coefficient(ADC)of the primary tumor,the volume of primary tumor(GTVnx),the volume of the primary tumor+the volume of retropharyngeal lymph nodes(GTVnx+RLN),and the tumor blood flow(TBF)of ASL quantitative perfusion parameters were compared between effective 73 case and ineffective patients(30 case)before and after chemoradiotherapy.The receiver operating characteristics(ROC)curves were used to evaluate the value of ADC,GTVnx,GTVnx+RLN and TBF in predicting the efficacy of chemoradiotherapy in nasopharyngeal carcinoma patients.Univariate method was used to analyze the basic data of patients,and Logistic regression model was used to analyze the related factors of chemoradiotherapy of locally advanced nasopharyngeal carcinoma.Results After concurrent chemoradiotherapy,73 patients were included in the effective group,including 36 patients achieving complete remission(CR)and 37 patients achieving partial remission(PR);30 patients were included in the ineffective group,including 25 patients achieving stable disease(SD)and 5 patients achieving disease progression(PD).Before and after treatment,ADC,GTVnx,GTVnx+RLN in the effective group were significantly lower than those in the ineffective group,and TBF in the effective group was higher than that in the ineffective group(P<0.05).The changes of ADC,GTVnx,GTVnx+RLN,and TBF before and after concurrent chemoradiotherapy in the effective group were significantly higher than those in the ineffective group(P<0.05).The area under the curve(AUC)values of ADC,GTVnx,GTVnx+RLN,and TBF for predicting the efficacy of concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma were 0.727,0.555,0.753,and 0.791,respectively.The results of logistic regression model showed that high levels of ADC,GTVnx and GTVnx+RLN,low level of TBF,TNM stage Ⅳ,and low tumor differentiation before treatment were independent risk factors for poor efficacy of concurrent chemoradiotherapy in nasopharyngeal carcinoma patients(P<0.05).Conclusion Elevated baseline of ADC,GTVnx and GTVnx+RLN and reduced TBF are correlated with poorer outcomes following chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma,serving as potential predictive biomarkers.

Objective : To explore the effects of the antihypertensive drug Amlodipine on calcium influx and autoph- agy in human podocytes ( HPC) ． Methods : HPC cells were routinely cultured in vitro． HPC cells were treated with angiotensin Ⅱ ( Ang Ⅱ ) ，the L-type Ca2 + blocker Amlodipine alone or in combination．The Ca2 + imaging system was used to detect the transient changes in the intracellular Ca2 + flux of HPC cells in real time after drug treatment．Western blot was employed to detect the changes in the ratio of autophagy marker proteins LC3B-Ⅱ/ LC3B-Ⅰ , and the expression levels of Beclin-1，P62，as well as apoptosis-related proteins Bcl-2 and Bax．Flow cytometry was used to detect the number of Fluo-4AM positive cells at 488 nm to analyze the level of intracellular Ca2 + influx in HPC cells．Lyso-Tracker Green live cell staining was applied to analyze the fluorescence intensity of lysosomes．Flow cytometry was also used to detect the apoptosis rate of HPC cells． Results : Compared with the control group，in the Ang Ⅱ group，the transient Ca2 + flux and the number of Fluo-4AM positive cells increased significantly (P＜0. 001) ．The ratio of autophagy marker proteins LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 001) and the pro- tein expression of Beclin-1 (P＜0. 01) decreased significantly，while the expression of P62 increased (P＜0. 01) ． The fluorescence intensity of lysosomes weakened (P＜0. 05) ，the apoptosis rate increased (P＜0. 0001) ，the ex- pression of apoptosis-related protein Bcl-2 decreased (P ＜0. 01 ) ，and the protein level of Bax increased (P < 0. 001) ．Compared with the control group，in the Amlodipine group，the number of Fluo-4AM positive cells de- creased significantly (P＜0. 001) ，the ratio of LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 001) and the protein expression of Bec- lin-1 (P＜0. 001) increased，the protein expression of P62 decreased (P＜0. 05) ，the fluorescence intensity of ly- sosomes enhanced (P＜0. 01) ，the apoptosis rate decreased (P＜0. 01) ，the protein expression of Bcl-2 increased (P＜0. 001) ，and the protein level of Bax decreased (P＜0. 001) ．Compared with the Ang Ⅱ group，in the Ang Ⅱ + Amlodipine group，the number of Fluo-4AM positive cells decreased significantly (P＜0. 001) ，the ratio of LC3B-Ⅱ/ LC3B-Ⅰ (P＜0. 01) and the protein expression of Beclin-1 increased (P＜0. 05) ，the protein level of P62 decreased (P＜0. 01) ，the fluorescence intensity of lysosomes increased (P ＜0. 05) ，the apoptosis rate de- creased (P＜0. 001) ，the protein expression of Bcl-2 increased (P ＜0. 001 ) ，and the protein level of Bax de- creased (P＜0. 001) ． Conclusion Amlodipine inhibits calcium influx，promotes autophagy and inhibits apoptosis in human podocytes，which is useful in preventing the development of hypertensive nephropathy．

Objective To investigate the preoperative prediction of the expression level of programmed cell death ligand 1(PD-L1)in non-small cell lung cancer(NSCLC)by a nomogram model constructed with clinical data,conventional CT signs and spectral CT parameters.Methods A retrospective analysis was conducted on 52 patients with pathologically confirmed NSCLC and undergoing preoperative spectral CT examination.The patients were categorized into positive and negative groups according to PD-L1 expression level,and their clinical data,conventional CT signs and spectral CT parameters were collected.Specifically,clinical data included gender,age,Ki-67 and tumor markers;conventional CT signs included tumor density,margins,calcification,spiculation,lobulation,pleural indentation and cavitation;and spectral CT parameters measured in the arterial and venous phases included effective atomic number(Eff-Z),iodine concentration(IC),water concentration(WC)and normalized iodine concentration(NIC).Intergroup differences were analyzed,and multivariate Logistic regression was used to identify independent predictors and establish the prediction model which was evaluated for prediction performance and accuracy using receiver operating characteristic(ROC)curves,calibration curve and decision curve analyses.Results For clinical data,only the difference in gender between two groups had statistical significance(P<0.05).The spectral CT parameters(IC,NIC and Eff-Z)in the arterial and venous phases of PD-L1 positive group were all greater than those of PD-L1 negative group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis identified gender(P=0.024),venous-phase Eff-Z(P=0.002),and venous-phase IC(P=0.003)as independent predictive factors for PD-L1 expression.The nomogram prediction model constructed with these independent predictors had an area under curve of 0.80,a sensitivity of 88.00%,and a specificity of 59.00%.The calibration curve showed that the predicted values had a high consistency with the actual values.The decision curve revealed that when the high-risk threshold was between 0.10 and 0.83,the model could achieve the maximum net benefit.Conclusion The nomogram model constructed with spectral CT parameters and clinical data has certain value in predicting the expression level of PD-L1 in NSCLC.

Objective:To analyze the CT and MRI manifestations of hepatic angiomyolipoma (HAML) to improve the diagnostic accuracy of HAML.Methods:A retrospective analysis was conducted on the clinical data of 46 cases of HAML confirmed by tumor surgery or biopsy in Yueqing People's Hospital of Zhejiang and Rui'an People's Hospital of Zhejiang from November 2015 to June 2024. Among them, there were 20 males and 26 females, with an average age of (40±18) years. The CT and MRI manifestations of the patients were recorded, and the tumor location, size, shape, boundary, CT density, T 1-weighted imaging, T 2-weighted imaging, diffusion-weighted imaging (DWI), fat suppression sequence, and inverse phase signal were observed. Results:29 cases underwent plain CT scan combined with enhanced scan. Among them, 4 cases (13.8%) had a round shape, 22 cases (47.8%) had a nearly round shape, and 3 cases (10.3%) had an irregular shape. 26 cases (89.7%) had clear boundaries, and 3 cases (10.3%) had unclear boundaries. 5 cases (17.2%) had uniform density, and 24 cases (82.8%) had non-uniform density. The CT value of the tumor was (32±6.8) Hu. 25 cases (86.2%) contained fat tissue within the tumor. Among them, 13 cases (44.8%) were mixed type. After enhancement, the fat tissue and necrotic cystic changes did not enhance, and the soft tissue components showed varying degrees of enhancement in the arterial phase. Among them, 6 cases continued to enhance in the portal venous phase and delayed phase, showing " fast in and slow out" , and 7 cases showed decreased enhancement in the portal venous phase and delayed phase, showing " fast in and fast out" . 17 cases underwent plain MRI scan combined with enhanced scan. Among them, 12 cases were mixed type. On T 2-weighted imaging with fat suppression, it was a mixed high signal, on T 1-weighted imaging, it was an isointense/low signal or mixed low signal, and on DWI, it was a high signal, with partial signal reduction on the inverse phase. 9 cases of tumor septation showed isointense signals on T 1-weighted imaging, 7 cases showed isointense signals on T 2-weighted imaging, and 2 cases showed high signals on T 2-weighted imaging. After enhancement, the mass showed heterogeneous enhancement, with 7 cases showing " fast in and fast out" and 5 cases showing " fast in and slow out" . Conclusion:Plain CT scan shows that HAML is round or nearly round, with non-uniform low density or uniform isodensity. Plain MRI scan shows isointense or slightly high signal on T 2-weighted imaging, low signal on T 1-weighted imaging, and high signal on T 2-weighted imaging with fat suppression. After enhancement, there is significant or mild to moderate enhancement in the arterial phase, with " fast in and fast out" or " fast in and slow out" as the characteristics.

Objective To investigate the preoperative prediction of the expression level of programmed cell death ligand 1(PD-L1)in non-small cell lung cancer(NSCLC)by a nomogram model constructed with clinical data,conventional CT signs and spectral CT parameters.Methods A retrospective analysis was conducted on 52 patients with pathologically confirmed NSCLC and undergoing preoperative spectral CT examination.The patients were categorized into positive and negative groups according to PD-L1 expression level,and their clinical data,conventional CT signs and spectral CT parameters were collected.Specifically,clinical data included gender,age,Ki-67 and tumor markers;conventional CT signs included tumor density,margins,calcification,spiculation,lobulation,pleural indentation and cavitation;and spectral CT parameters measured in the arterial and venous phases included effective atomic number(Eff-Z),iodine concentration(IC),water concentration(WC)and normalized iodine concentration(NIC).Intergroup differences were analyzed,and multivariate Logistic regression was used to identify independent predictors and establish the prediction model which was evaluated for prediction performance and accuracy using receiver operating characteristic(ROC)curves,calibration curve and decision curve analyses.Results For clinical data,only the difference in gender between two groups had statistical significance(P<0.05).The spectral CT parameters(IC,NIC and Eff-Z)in the arterial and venous phases of PD-L1 positive group were all greater than those of PD-L1 negative group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis identified gender(P=0.024),venous-phase Eff-Z(P=0.002),and venous-phase IC(P=0.003)as independent predictive factors for PD-L1 expression.The nomogram prediction model constructed with these independent predictors had an area under curve of 0.80,a sensitivity of 88.00%,and a specificity of 59.00%.The calibration curve showed that the predicted values had a high consistency with the actual values.The decision curve revealed that when the high-risk threshold was between 0.10 and 0.83,the model could achieve the maximum net benefit.Conclusion The nomogram model constructed with spectral CT parameters and clinical data has certain value in predicting the expression level of PD-L1 in NSCLC.