ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid （23-HBA）， a key constituent of Pulsatillae Radix， on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-（methylnitrosamino）-1-（3-pyridyl）-1-butanone （NNK） and lipopolysaccharide （LPS） in mice， alongside exploring its influence on immune cells and delving into the underlying mechanisms. MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control， model， aspirin （10 mg·kg^-1）， and low-， medium-， and high-dose （3.75， 7.5， 15 mg·kg^-1， respectively） 23-HBA groups. The treatment lasted for 26 weeks， after which the spleen， lung， and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 （TTF-1）， neuron-specific enolase （NSE）， and proliferating cell nuclear antigen （Ki-67） in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages， myeloid-derived suppressor cells （MDSCs）， and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 （JAK2）， Src homology 2 domain-containing phosphatase 2 （SHP2）， and suppressor of cytokine signaling 3 （SOCS3）. Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 （p-STAT3）， p53， and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA. ResultsCompared with the normal group， the lung and spleen indexes of the model group were increased to varying degrees （P<0.05， P<0.01）， the expression of TTF-1， NSE and Ki-67 protein was significantly increased （P<0.05， P<0.01）， and the serum levels of TNF-α， IL-1β and IL-6 were significantly increased （P<0.01）. The number of macrophages in the model group was significantly decreased （P<0.01）， and the number of exhausted T cells and MDSCs was significantly increased （P<0.05， P<0.01）. Compared with the model group， the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly （P<0.05）， and the lung index of mice in the middle dose group of 23-HBA decreased significantly （P<0.05）. The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group （P<0.05， P<0.01）. The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group （P<0.05， P<0.01）. The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased （P<0.05）， and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased （P<0.05， P<0.01）. The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased （P<0.05）， and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased （P<0.05， P<0.01）. In addition， 23-HBA had strong molecular docking ability to SHP2， SOCS3 and JAK2 （≥7 kcal·mol^-1）， and significantly down-regulated the protein levels of p-STAT3， SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma （P<0.01）. Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses， improving the tumor immune microenvironment， and regulating key signaling pathways.

Objective:To evaluate the clinical efficacy of mitral valve transcatheter edge-to-edge repair (TEER) in patients with non-central degenerative mitral regurgitation (DMR).Methods:This retrospective study included patients with non-central DMR who underwent TEER at Fuwai Hospital between January 2021 and February 2024. Patients were categorized into two groups: the commissure-involved group and the non-commissure group, based on whether the mitral valve commissures were involved. Clinical data, surgical outcomes, and echocardiographic findings at 3 months postoperatively were collected and compared, and patients were followed up. The primary endpoint was the procedural success rate at discharge.Results:A total of 59 patients were included, aged (68.6±9.3) years, including 23 females (39%). In the overall study population, 78% (46/59) of patients had severe mitral regurgitation. Forty-two cases were in the non-commissure group, and 17 cases were in the commissure-involved group. Patients in the non-commissure group mainly had lesions in the A1/P1 region, while patients in the commissure-involved group mainly had lesions in the A3/P3 region. There was no significant difference in the procedural success rate at discharge (93% vs. 88%, P=0.95) and the incidence of postoperative complications (5% vs. 6%, P=1.00) between the two groups. Two patients in the commissure-involved group experienced single leaflet device attachment, with one of them requiring conversion to surgical mitral valve surgery; In the non-commissure group, two patients experienced single-valve clamping, and one of them was converted to surgical mitral valve surgery. The follow-up time of the entire cohort was (15.5±10.3) months. In the non-commissure group, 2 patients died and 2 were readmitted. While in the commissure-involved group, no patients died and only 1 patient was readmitted. Conclusion:TEER is an effective treatment for patients with non-central DMR involving the commissures, without increasing the incidence of postoperative complications.

Purpose To explore the value of tumor intratumoral and peritumoral radiomics models based on dynamic contrast-enhanced MRI in predicting benign and malignant breast tumors.Materials and Methods This retrospective study analyzed clinical data and MRI imaging features from 309 patients with pathologically confirmed solitary breast tumors at the Second Affiliated Hospital of Xiamen Medical College from August 2018 to December 2022.The cohort was randomly divided into training(n=248)and testing(n=61)cohorts in an 8∶2 ratio.Using second-phase dynamic contrast-enhanced MRI images,five distinct peritumoral regions were segmented through 3D-Slicer software:intratumoral region,peritumoral 2 mm region,peritumoral 4 mm region,intratumoral combined with peritumoral 2 mm region and intratumoral combined with peritumoral 4 mm region.Radiomic features were extracted from these regions of interest.Machine learning algorithms integrated with Logistic regression analysis were employed for feature selection,with cross-validation techniques determining the optimal radiomic signature combination.Results Of 309 patients,150 were benign tumors and 159 were malignant tumors.The age,maximum diameter and enhancement type of benign and malignant breast tumors were statistically significant(Z/χ2=-7.695,-5.775,30.248;all P<0.001).For the region of interest of intratumoral combined with peritumoral 4 mm region,the area under curve,sensitivity,specificity,accuracy and F1 scores of the training and validation were 0.893,89.1%,75.0%,82.3%,0.838 and 0.881,74.2%,86.7%,80.3%,0.793,respectively.In the training set,the area under curve of intratumoral combined with peritumoral 4 mm region was significantly higher than that of intratumoral,peritumoral 2 mm,peritumoral 4 mm and intratumoral combined with peritumoral 2 mm regional imaging models(Z=2.506,2.982,3.392,2.157;all P<0.05).The Hosmer-Lemeshow test showed that the calibration curve of the model combined with region of interest of intratumoral combined with peritumoral 4 mm region was highly consistent with the ideal curve(training P=0.381,validation P=0.159).The decision curve indicated that the net benefit of the radiomics model in the region of interest of intratumoral combined with peritumoral 4 mm region was the highest when the risk threshold was between 0 and 1.0.Conclusion The radiomics model has good predictive performance in predicting benign or malignant breast tumors,among them the combined region of interest of intratumoral combined with peritumoral 4 mm region provides the best performance and highest benefit.The technology clinical application will provide a non-invasive predictive method for the differential diagnosis of benign and malignant breast tumors.

Lung cancer is a serious pulmonary tumor,with exacerbation of chronic lung inflammation being a precursor to the development of lung cancer.Relevant animal models are widely used in experimental research,to gain a deeper understanding of the pathogenesis of lung cancer and to develop preventive treatment strategies.Induced lung cancer animal models are of particular importance for understanding the transition from chronic lung inflammation to lung cancer.Early intervention is crucial for the prevention and treatment of lung cancer.Here we review the recent literature regarding the inducing factors for lung cancer,including carcinogens(e.g.nicotine-derived nitrosamine ketone,benzopyrene,diethylnirtosamine atmospheric fine particulate matter(PM2.5),coal smoke,heavy metal ions,radiation,and biological infections).We also summarize animal models of lung inflammation and cancer transformation induced by these factors,discuss the mechanisms by which relevant carcinogens induce lung cancer,analyze the advantages and limitations of the animal models,and consider future development directions.This review aims is to provide a valuable reference for the future establishment of relevant models.

Lung cancer is a serious pulmonary tumor,with exacerbation of chronic lung inflammation being a precursor to the development of lung cancer.Relevant animal models are widely used in experimental research,to gain a deeper understanding of the pathogenesis of lung cancer and to develop preventive treatment strategies.Induced lung cancer animal models are of particular importance for understanding the transition from chronic lung inflammation to lung cancer.Early intervention is crucial for the prevention and treatment of lung cancer.Here we review the recent literature regarding the inducing factors for lung cancer,including carcinogens(e.g.nicotine-derived nitrosamine ketone,benzopyrene,diethylnirtosamine atmospheric fine particulate matter(PM2.5),coal smoke,heavy metal ions,radiation,and biological infections).We also summarize animal models of lung inflammation and cancer transformation induced by these factors,discuss the mechanisms by which relevant carcinogens induce lung cancer,analyze the advantages and limitations of the animal models,and consider future development directions.This review aims is to provide a valuable reference for the future establishment of relevant models.

Purpose To explore the value of tumor intratumoral and peritumoral radiomics models based on dynamic contrast-enhanced MRI in predicting benign and malignant breast tumors.Materials and Methods This retrospective study analyzed clinical data and MRI imaging features from 309 patients with pathologically confirmed solitary breast tumors at the Second Affiliated Hospital of Xiamen Medical College from August 2018 to December 2022.The cohort was randomly divided into training(n=248)and testing(n=61)cohorts in an 8∶2 ratio.Using second-phase dynamic contrast-enhanced MRI images,five distinct peritumoral regions were segmented through 3D-Slicer software:intratumoral region,peritumoral 2 mm region,peritumoral 4 mm region,intratumoral combined with peritumoral 2 mm region and intratumoral combined with peritumoral 4 mm region.Radiomic features were extracted from these regions of interest.Machine learning algorithms integrated with Logistic regression analysis were employed for feature selection,with cross-validation techniques determining the optimal radiomic signature combination.Results Of 309 patients,150 were benign tumors and 159 were malignant tumors.The age,maximum diameter and enhancement type of benign and malignant breast tumors were statistically significant(Z/χ2=-7.695,-5.775,30.248;all P<0.001).For the region of interest of intratumoral combined with peritumoral 4 mm region,the area under curve,sensitivity,specificity,accuracy and F1 scores of the training and validation were 0.893,89.1%,75.0%,82.3%,0.838 and 0.881,74.2%,86.7%,80.3%,0.793,respectively.In the training set,the area under curve of intratumoral combined with peritumoral 4 mm region was significantly higher than that of intratumoral,peritumoral 2 mm,peritumoral 4 mm and intratumoral combined with peritumoral 2 mm regional imaging models(Z=2.506,2.982,3.392,2.157;all P<0.05).The Hosmer-Lemeshow test showed that the calibration curve of the model combined with region of interest of intratumoral combined with peritumoral 4 mm region was highly consistent with the ideal curve(training P=0.381,validation P=0.159).The decision curve indicated that the net benefit of the radiomics model in the region of interest of intratumoral combined with peritumoral 4 mm region was the highest when the risk threshold was between 0 and 1.0.Conclusion The radiomics model has good predictive performance in predicting benign or malignant breast tumors,among them the combined region of interest of intratumoral combined with peritumoral 4 mm region provides the best performance and highest benefit.The technology clinical application will provide a non-invasive predictive method for the differential diagnosis of benign and malignant breast tumors.

Objective:To evaluate the clinical efficacy of mitral valve transcatheter edge-to-edge repair (TEER) in patients with non-central degenerative mitral regurgitation (DMR).Methods:This retrospective study included patients with non-central DMR who underwent TEER at Fuwai Hospital between January 2021 and February 2024. Patients were categorized into two groups: the commissure-involved group and the non-commissure group, based on whether the mitral valve commissures were involved. Clinical data, surgical outcomes, and echocardiographic findings at 3 months postoperatively were collected and compared, and patients were followed up. The primary endpoint was the procedural success rate at discharge.Results:A total of 59 patients were included, aged (68.6±9.3) years, including 23 females (39%). In the overall study population, 78% (46/59) of patients had severe mitral regurgitation. Forty-two cases were in the non-commissure group, and 17 cases were in the commissure-involved group. Patients in the non-commissure group mainly had lesions in the A1/P1 region, while patients in the commissure-involved group mainly had lesions in the A3/P3 region. There was no significant difference in the procedural success rate at discharge (93% vs. 88%, P=0.95) and the incidence of postoperative complications (5% vs. 6%, P=1.00) between the two groups. Two patients in the commissure-involved group experienced single leaflet device attachment, with one of them requiring conversion to surgical mitral valve surgery; In the non-commissure group, two patients experienced single-valve clamping, and one of them was converted to surgical mitral valve surgery. The follow-up time of the entire cohort was (15.5±10.3) months. In the non-commissure group, 2 patients died and 2 were readmitted. While in the commissure-involved group, no patients died and only 1 patient was readmitted. Conclusion:TEER is an effective treatment for patients with non-central DMR involving the commissures, without increasing the incidence of postoperative complications.

Objective:To propose recommendations for noise protection and control measures in high-performance fighter cockpits by investigating the noise exposure of pilots in cockpits.Methods:In the ground test for 3 types of high-performance fighters (J-A, J-B and J-C), the total sound pressure level (SPL), A sound level, as well as the linear SPL at 31.5, 63, 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz were respectively measured by the sound level meter installed at ear position of a dummy pilot in cockpit and at 2.5 m away along the line started at right tail nozzle and 60° off the aircraft longitudinal axis when the engine accelerated to its maximum speed for 5-180 s. Ten young male volunteers with normal hearing were selected to use 125, 250, 500, 1 000, 2 000, 4 000, 8 000 Hz octave center frequency narrowband signals, respectively, to test their hearing thresholds with and without 3 types of flight helmet (imported, in-service, and newly developed) under active and passive noise reduction conditions. The sound attenuation values of the helmets (difference between the bare-ear threshold and the threshold with the helmet) were calculated.Results:The total SPL at the ear position of the dummy pilot in the cockpits of J-A, J-B, and J-C during ground test at maximum engine operation was 102.2, 100.4, 111.2 dB, respectively; the total SPL at the tail nozzle of J-B and J-C was 134.4, 148.0 dB, respectively. The cockpit noise of J-C exceeded the limit standard of GJB 565A—2009. Except for the measure at 4 000 Hz, the sound attenuation values of different helmets at other frequencies were significantly different ( H=35.49, 38.93, 32.37, 33.50, 23.96, 27.81, all P<0.001). By attenuating under active state of Type B helmet, the total noise exposure SPL in the cockpits of J-A, J-B, and J-C was 87.3, 84.1, 89.3 dB, respectively. Conclusions:The noise in high performance aircraft cockpit still exposes pilot in relatively high SPL. It still poses the potential threat to pilot′s hearing health and performance. Helmet noise attenuation needs further development. The active attenuation of helmet, as well as the reduction of the source noise level is still the main goal of noise protection.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

ObjectiveTo investigate the protective effect and mechanism of Euphorbia helioscopia aqueous extract （EHE） on mice with chronic obstructive pulmonary disease （COPD） and its influence on precancerous lesion-associated proteins in lung tissues induced by cigarette smoke （CS）. MethodThe COPD model was induced by CS in 60 mice and the model mice were randomly divided into control group， model group， positive drug group （dexamethasone， 2 mg·kg^-1）， and low-， medium-， and high-dose EHE groups （1.875， 3.75， 7.5 g·kg^-1）. The high-performance liquid chromatography （HPLC） method was used to determine the related components in EHE. The changes in end-expiratory pause （EEP）， airway resistance （Penh）， expiratory flow at 50% vital capacity （EF50）， and other pulmonary function indexes were detected by the spirometer. The levels of inflammatory factors， such as interleukin （IL）-2， IL-5， IL-18， IL-17A， and IL-27 in bronchoalveolar lavage fluid （BALF） of mice were detected by high-throughput liquid protein chip technology. Hematoxylin-eosin （HE） staining was used to detect the pathological changes in lung tissues in mice. The content of malondialdehyde （MDA）， myeloperoxidase （MPO）， and glutathione peroxidase （GSH-Px） in lung tissues was determined by the colorimetric method. The mRNA relative expression of tumor necrosis factor-α （TNF-α）， transforming growth factor-β （TGF-β）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and matrix metalloproteinase-12 （MMP-12） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Immunohistochemistry （IHC） was used to detect the expression of tumor protein （P53） and cell proliferation-associated antigen （Ki67） in lung tissues， and Western blot was used to detect the relative expression of tumor suppressor protein （P16）， DNA （cytosine-5）-methyltransferase 1 （DNMT1）， and fragile histidine triad （FHIT） in lung tissues. ResultThe results showed that the main compounds in EHE included phenols （gallic acid and protocatechuic acid） and flavonoids （such as hyperoside， rutin， myricetin， naringenin， quercetin， luteolin， kaempferol， and licorice chalcone A）， among which gallic acid and rutin were the highest in content. Compared with normal group， model group showed increased levels of EEP， EF50， and Penh （P<0.05）， and showed increased MDA and MPO levels （P<0.01） and decreased GSH-Px （P<0.01）， and the model group displayed increased levels of IL-2， IL-5， IL-18， IL-17A， IL-27， TNF-α， TGF-β， MMP-2， MMP-9， and MMP-12 （P<0.05）. And the model group exhibited up-regulated expression of P53， Ki67， and FHIT in lung tissues （P<0.01） and down-regulated expression of DNMT1 and P16 （P<0.01）. Compared with model group， the EHE groups showed decreased EEP and EF50 levels （P<0.05）. The pathological injury of lung tissues in mice of the model group was observed under HE staining， and the pathological injury of basal cell hyperplasia of lung tissues was gradually improved after treatment with EHE. The EHE groups showed reduced levels of MDA and MPO （P<0.01） and increased GSH-Px （P<0.01）. The EHE groups displayed decreased levels of IL-2， IL-5， IL-18， IL-17A， IL-27， TNF-α， TGF-β， MMP-2， MMP-9， and MMP-12 （P<0.05）. And the EHE groups showed down-regulated Ki67 and FHIT in lung tissues （P<0.05） and up-regulated expression of P53 and DNMT1 （P<0.05）. ConclusionEHE can protect mice from COPD and inhibit precancerous lesions， and the mechanism may be related to the inhibition of inflammation and oxidative stress response， regulation of protease and antiprotease imbalance， and regulation of epithelial cell growth.