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.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

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 formulate the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Methods:This was a qualitative study. This study was divided into 2 stages. The first stage of the study was conducted from June to August 2023 and involved the heads of the General Affairs Departments of the 47 community health service centers in Pudong New Area. These individuals completed online questionnaires to compile a database on the current status of matching supply and demand resources in community health service centers in Pudong New Area. The second stage of the study run from September 2023 to August 2024. Firstly, the functional modules of China′s community health service centers would be clarified through a literature review. The construction scale and design requirements of similar institutions at home and abroad would be benchmarked, as well as practical experience. The results of Phase 1 research would then be combined to form the " Community Health Service Center Infrastructure Configuration Requirements and Design Suggestions (Draft)". Then, relevant experts were brought together to discuss the draft and form the " Community Health Service Center Infrastructure Configuration Requirements and Design Recommendations (Revised Version)". The experts involved in the discussion specialized in the study of infrastructure resource allocation for medical institutions. Finally, the medical and healthcare system managers, community health service center users, and relevant commissions and bureaus of Pudong New Area were consulted to further revise and finalize the Guidelines for the Construction of Community Health Service Centers in Pudong New Area, Shanghai. Results:The total floor area of community health service centers in Pudong New Area was 57% (31/55), the number of beds per 1 000 people was 14% (8/55), and the total number of beds was 10% (6/60). These figures showed that urgent upgrades and construction in accordance with the new standards were required. The final " Guidelines for the Construction of Community Health Service Centers" of Shanghai Pudong New Area comprised 15 chapters, covering topics from the macro construction scale, site selection and general plan to architectural design, structural design, water supply and sewage treatment, ventilation and air conditioning, electrical systems, informatics, medical gas supply, indoor design, signage, marking and fire protection, etc. The guidelines have been revised to incorporate the functional design of the 5 basic rooms, with a particular focus on the creating humanistic spaces and promoting digitalization. Particular attention was paid to creating humanistic spaces and improving ageing with digital applications. Conclusions:The Guidelines for the Construction of Community Health Service Centers in Pudong New Area of Shanghai have been successfully formulated. These guidelines can be used to guide the subsequent high-quality and standardized development of community health service centers.

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 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 investigate the status of pain and influencing factors of patients with chronic wounds.Methods A convenience sampling was used to recruit 186 patients with chronic wounds from a tertiary hospital in Chongqing between January and August 2024.General information questionnaire,Numeric Rating Scale(NRS),and Chronic Wound Pain Status Questionnaire were used to collect data.Results The 186 patients had a median score for pain knowledge of 15(12,19),for pain attitude of 40(37,45),and for coping behaviors of 21(16,26).Generalized linear model analysis showed that age,education level,and per capita monthly household income were independent factors influencing pain knowledge(standardized regression coefficients:-1.625,2.071,1.209;95％CI:-2.479～-0.770,1.431～2.711,0.160～2.258,respectively;P＜0.05).Education level and baseline pain intensity were independent factors influencing pain attitude(standardized regression coefficients:3.036,-2.211;95％CI:2.146～3.926,-3.568～-0.854;P＜0.05).Education level and type of pain persistence were independent factors influencing coping behaviors to pain(standardized regression coefficients:1.001,-1.694;95％CI:0.194～1.809,-3.262～-0.126;P＜0.05).Conclusion Patients with chronic wounds have generally low levels of pain-related knowledge,attitudes,and coping behaviors.Age,per capita monthly household income,education level,and pain characteristics significantly influence their pain status.Education level plays a key role in influencing pain among patients with chronic wounds by shaping their access to pain-related knowledge,development of their attitudes toward pain,and execution of pain management behaviors.