1.Clinical application of an artificial intelligence system in predicting benign or malignant pulmonary nodules and pathological subtypes
Zhuowen YANG ; Zhizhong ZHENG ; Bin LI ; Yiming HUI ; Mingzhi LIN ; Jiying DANG ; Suiyang LI ; Chunjiao ZHANG ; Long YANG ; Liang SI ; Tieniu SONG ; Yuqi MENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1086-1095
Objective To evaluate the predictive ability and clinical application value of artificial intelligence (AI) systems in the benign and malignant differentiation and pathological type of pulmonary nodules, and to summarize clinical application experience. Methods A retrospective analysis was conducted on the clinical data of patients with pulmonary nodules admitted to the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from February 2016 to February 2025. Firstly, pulmonary nodules were divided into benign and non-benign groups, and the discriminative abilities of AI systems and clinicians were compared. Subsequently, lung nodules reported as precursor glandular lesions (PGL), microinvasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) in postoperative pathological results were analyzed, comparing the efficacy of AI systems and clinicians in predicting the pathological type of pulmonary nodules. Results In the analysis of benign/non-benign pulmonary nodules, clinical data from a total of 638 patients with pulmonary nodules were included, of which there were 257 males (10 patients and 1 patient of double and triple primary lesions, respectively) and 381 females (18 patients and 1 patient of double and triple primary lesions, respectively), with a median age of 55.0 (47.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis of the two groups of variables showed that, except for nodule location, the differences in the remaining variables were statistically significant (P<0.05). Multivariate logistic regression analysis showed that age, nodule type (subsolid pulmonary nodule), average density, spicule sign, and vascular convergence sign were independent influencing factors for non-benign pulmonary nodules, among which age, nodule type (subsolid pulmonary nodule), spicule sign, and vascular convergence sign were positively correlated with non-benign pulmonary nodules, while average density was negatively correlated with the occurrence of non-benign pulmonary nodules. The area under the receiver operating characteristic curve (AUC) of the malignancy risk value given by the AI system in predicting non-benign pulmonary nodules was 0.811, slightly lower than the 0.898 predicted by clinicians. In the PGL/MIA/IAC analysis, clinical data from a total of 411 patients with pulmonary nodules were included, of which there were 149 males (8 patients of double primary lesions) and 262 females (17 patients of double primary lesions), with a median age of 56.0 (50.0, 61.0) years. Different lesions in the same patient were analyzed as independent samples. Univariate analysis results showed that, except for gender, nodule location, and vascular convergence sign, the differences in the remaining variables among the three groups of PGL, MIA, and IAC patients were statistically significant (P<0.05). Multinomial multivariate logistic regression analysis showed that the differences between the parameters in the PGL group and the MIA group were not statistically significant (P>0.05), and the maximum diameter and average density of the nodules were statistically different between the PGL and IAC groups (P<0.05), and were positively correlated with the occurrence of IAC as independent risk factors. The average AUC value, accuracy, recall rate, and F1 score of the AI system in predicting lung nodule pathological type were 0.807, 74.3%, 73.2%, and 68.5%, respectively, all better than the clinical physicians’ prediction of lung nodule pathological type indicators (0.782, 70.9%, 66.2%, and 63.7% respectively). The AUC value of the AI system in predicting IAC was 0.853, and the sensitivity, specificity, and optimal cutoff value were 0.643, 0.943, and 50.0%, respectively. Conclusion This AI system has demonstrated high clinical value in predicting the benign and malignant nature and pathological type of lung nodules, especially in predicting lung nodule pathological type, its ability has surpassed that of clinical physicians. With the optimization of algorithms and the adequate integration of multimodal data, it can better assist clinical physicians in formulating individualized diagnostic and treatment plans for patients with lung nodules.
2.Oleanolic acid regulates Treg/Th17 cell imbalance in allergic rhinitis by inhibiting autophagy
Li WANG ; Yongyang HUANG ; Yi ZHANG ; Bin QI ; Long WAN ; Yanping DU ; Caisheng CHEN
Chinese Journal of Immunology 2024;40(7):1399-1404
Objective:To explore effect of oleanolic acid on allergic rhinitis(AR)and its potential mechanism.Methods:Peripheral blood mononuclear cells(PBMCs)were isolated by density gradient centrifugation.Real-time quantitative PCR was used to detect expressions of Foxp3,IL-17A,Beclin1,and RORγt mRNA in nasal mucosa;flow cytometry was employed to assess proportion of Treg and Th17 cells in PBMCs;Western blot was utilized to determine expressions of RORγt,LC3-Ⅰ,LC3-Ⅱ,Beclin1,and P62 proteins in nasal mucosal.Mice were randomly divided into Control,ovalbumin(OVA),L-oleanolic acid,H-oleanolic acid,DSGC,3-MA and H-oleanolic acid+Rapa groups.Histological changes were observed by HE staining and Periodate Schiff(PAS)staining.Serological changes,expressions of IL-17A,IL-10,eosinophilic cationic protein(ECP)and anti-OVA-specific antibodies were detected by ELISA.Results:AR patients had Th17/Treg imbalance and activated autophagy.Oleanolic acid restored Th17/Treg balance and inhibited autophagy in vitro.In vivo experiments demonstrated that oleanolic acid inhibited OVA-induced allergic nasal symptoms and activation of autophagy pathway,which was same as regulation of 3-MA,while Rapa could weaken effects of high dose of oleanolic acid.Moreover,oleanolic acid reduced infiltration of different inflammatory cells of nasal lavage fluid,prevented damages to epithelial cells,and improved nasal mucosal thickness and mucus secretion.Oleanolic acid regulated balance of mouse Th17/Treg-associated cytokines expressions.Conclusion:Oleanolic acid can be used to treat AR,whose effect is realized through inhibiting autophagy to regulate Th17/Treg balance.
3.Allyl isothiocyanate exacerbates acute toxoplasmosis through inhibition of inflammatory cytokines
Qiu-Mei LIN ; Hong-Bin LONG ; Jun-Ting HE ; Zhi-hao ZHANG ; Ho-Woo NAM ; Fu-Shi QUAN ; Qi ZHONG ; Xu-Qing LIU ; Zhao-Shou YANG
Parasites, Hosts and Diseases 2024;62(4):476-483
Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.
4.Therapeutic effect of Lingze Tablets on benign prostatic hyperplasia in rats:An exploration based on the VEGFA/TNF/IL-6 signaling pathway
Hua-Nan ZHANG ; Song SUN ; Jun-Long FENG ; Yi-Chen LIU ; Hai-Song LI ; Jin-Sheng WANG ; Bin WANG
National Journal of Andrology 2024;30(7):634-639
Objective:To explore the mechanism of Lingze Tablets(LZT)acting on BPH in rats based on the VEGFA/TNF/IL-6 signaling pathway.Methods:We equally randomized 30 SPF SD male rats into five groups,normal control,BPH model con-trol,low-dose LZT,medium-dose LZT and high-dose LZT,and established a BPH model in the latter four groups by induction with non-castrate testosterone propionate.After the modeling,we treated the rats in the normal and model groups by intragastrical adminis-tration of physiological saline,and those in the latter three groups with low-,medium-,and high-dose LZT respectively,all for 28 suc-cessive days.Then we collected the prostate tissue from the animals for observation of the changes in the prostatic indexes and histo-morphology,detected the expressions of the proteins related to the VEGFA/TNF/IL-6 signaling pathway,and compared the data ob-tained among different groups.Results:Compared with the normal controls,the rats in the model control group showed significant pros-tatic hyperplasia,markedly increased prostatic index([0.84±0.01]g,P<0.05),thickness of the prostatic epithelia and infiltra-tion of the luminal area,and dramatically up-regulated protein expressions of VEGFA(0.60±0.02,P<0.05),TNF(0.76±0.02,P<0.05)and IL-6(0.64±0.02,P<0.05).In comparison with the model controls,the rats in the low-,medium-and high-dose LZT groups exhibited significantly decreased prostatic indexes([0.76±0.02]g,[0.58±0.02]g and[0.52 0.01]g,all P<0.05),improved prostatic histomorphology,and down-regulated expressions of VEGFA(0.45±0.01,0.35±0.01 and 0.31±0.02,all P<0.05),TNF(0.45±0.01,0.33±0.01 and 0.27±0.01,all P<0.01)and IL-6(0.44±0.01,0.36±0.01 and 0.30±0.01,all P<0.01)in a dose-dependent manner.Conclusion:LZT produces therapeutic effect on BPH by negatively regulating the VEGFA/TNF/IL-6 signaling pathway,reducing the expression levels of VEGFA,TNF and IL-6 pro-teins,and regulating cell proliferation,apoptosis and inflammatory response.
5.Mechanisms of hypertension inducing erectile dysfunction via the cGMP/PKG signaling pathway:An investigation using transcriptomics and network pharmacology
Jun-Long FENG ; Hai-Song LI ; Song SUN ; Bin WANG ; Hua-Nan ZHANG ; Zi-Xiang GAO ; Peng-Ming MAO ; Long-Ji SUN ; Nian-Wen HUANG ; Ji-Sheng WANG
National Journal of Andrology 2024;30(9):771-781
Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P<0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P<0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P<0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.
6.Impact of bladder-neck angle on urination:An application study based on fluid-structure interaction
Xu-Dong JIA ; Xiao-Wan GUO ; Wan-Ze ZHANG ; Li-Juan LU ; Ya-Xuan WANG ; Kai-Long LIU ; Dong-Bin WANG ; Yue-Peng LIU ; Jin-Chun QI
National Journal of Andrology 2024;30(9):789-797
Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P<0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P<0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of<10,10-15 or>15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P<0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P<0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P<0.05)as well as between these two and the other three groups(P<0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P>0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P<0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.
7.Genetic variation and clinical characteristics of children with congenital hypothyroidism with different thyroid morphology: an analysis of 98 cases
Feng ZHANG ; Ying WANG ; Shuang LIU ; Leilei WANG ; Bin YU ; Wei LONG
Chinese Journal of Perinatal Medicine 2024;27(8):649-655
Objective:To explore the differences in genetic variations and clinical features of children with congenital hypothyroidism (CH) with different thyroid morphologies.Methods:A retrospective study was conducted on 98 children with CH diagnosed at Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, and Lianyungang Maternal and Child Health Care Hospital from August 19, 2011, to November 13, 2019. According to thyroid morphology, they were divided into the thyroid dysplasia (TD) group ( n=24), the gland-in-situ (GIS) group ( n=67), and the goiter group ( n=7). Whole exome sequencing was used to detect genetic variants, and pathogenic, likely pathogenic variants, and variants of uncertain significance were defined as potential functional variants. General condition, genetic variants, and treatment were compared between the three groups. Statistical analysis was performed using Chi-square and Bonferroni correction tests, Kruskal-Wallis test, or Mann-Whitney U test. Results:(1) The proportion of female infants in the TD group was higher than that in the GIS and goiter groups [87.5% (21/24) vs.47.8% (32/67) and 3/7, Bonferroni correction, respectively, both P<0.017]. The difference in serum thyroid stimulating hormone levels when diagnosed with CH was statistically significant in the TD, GIS, and goiter groups [128.00 mU/L (33.30-208.00 mU/L), 55.40 mU/L (17.73-116.00 mU/L), and 32.00 mU/L (21.55-57.65 mU/L), H=7.02, P=0.030], but was not statistically significant in pairwise comparisons (all P>0.017). (2) The detection rates of potential functional variants in the TD, GIS, and goiter groups were 45.8% (11/24), 88.1% (59/67), and 6/7, respectively, and the detection rate in the GIS group was higher than that in the TD group (Bonferroni correction, P<0.001). The detection rate of potential functional variants in DUOX2 gene was the highest [59.2% (58/98)], which was 20.8% (5/24), 73.1% (49/67), and 4/7 in the TD, GIS, and goiter groups, respectively, with statistically significant differences between groups ( χ2=20.02, P<0.001). Single allele variants were more common in the TD group (7/11), while double allele variants were more common in the GIS and goiter groups [71.2% (42/59) and 4/6, respectively], in addition, six cases of oligogenic variants were detected in the GIS group (10.2%, 6/59). (3) The difference in the dose of levothyroxine (μg/d) administered to children in the TD, GIS, and goiter groups was statistically significant at 2 years of age [37.50 (25.00-45.00), 25.00 (16.60-25.00), and 25.00 (16.50-40.00), H=16.53] and 3 years of age [37.50 (27.12-47.50), 20.00 (6.25-29.25), and 31.25 (9.38-52.50), H=14.16] (all P<0.001), and the dose of levothyroxine administered in the TD group was higher than that of the GIS group at the age of 2 and 3 years ( Z were -4.06 and -3.75, both P<0.017). Conclusions:The detection rate of underlying functional variants varies among children with CH with different thyroid morphologies. DUOX2 gene variants are the most prevalent and double allele variants are common. Infants and toddlers with TD may require higher doses of levothyroxine as they grow.
8.Allyl isothiocyanate exacerbates acute toxoplasmosis through inhibition of inflammatory cytokines
Qiu-Mei LIN ; Hong-Bin LONG ; Jun-Ting HE ; Zhi-hao ZHANG ; Ho-Woo NAM ; Fu-Shi QUAN ; Qi ZHONG ; Xu-Qing LIU ; Zhao-Shou YANG
Parasites, Hosts and Diseases 2024;62(4):476-483
Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.
9.Allyl isothiocyanate exacerbates acute toxoplasmosis through inhibition of inflammatory cytokines
Qiu-Mei LIN ; Hong-Bin LONG ; Jun-Ting HE ; Zhi-hao ZHANG ; Ho-Woo NAM ; Fu-Shi QUAN ; Qi ZHONG ; Xu-Qing LIU ; Zhao-Shou YANG
Parasites, Hosts and Diseases 2024;62(4):476-483
Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.
10.The correlation analysis of coronary artery plaque AI quantitative parameter with FFR-CT in coronary CT angiography
Qingdong YAO ; Chengbing ZHANG ; Jun FU ; Peng WANG ; Bin LONG ; Haifeng LIU
The Journal of Practical Medicine 2024;40(17):2489-2494
Objective To investigate the relationship between coronary artery plaque AI quantitative parameter and FFR-CT in coronary computed tomography angiography.Methods A total of 84 patients suspected of having CAD[52 males and 32 females,aged 27 to 81 years with a mean age of(58.1±11.9)years]were enrolled in this study.All patients underwent coronary computed tomography angiography.The CCTA data was processed using shukun(SK)software for labeling and analysis of the coronary arteries,as well as obtaining quantitative parameters of coronary artery plaque AI and corresponding FFR-CT values.The quantitative parameters included plaque length,total volume,minimum lumen area(MLA),minimal lumen degree(MLD),lipid composition volume and proportion,fibrous-lipid composition volume and proportion,fibrous composition volume and proportion,calcified composition volume and proportion.Coronary artery hemodynamic abnormality or myocardial ischemia was defined as an FFR-CT value≤0.8.Correlational analysis was performed to evaluate the association between AI plaque quantitative param-eters and FFR-CT values.Univariate and multivariate binary logistic regression analyses were conducted to identify independent risk factors for predicting FFR-CT≤0.8.The predictive performance of the model based on AI plaque quantitative parameters was assessed using receiver operating characteristic(ROC)curve analysis and calculation of the area under the curve(AUC).Sensitivities,specificities,diagnostic test accuracy rates were also calculated.Results The predominant symptoms observed in the cohort of 84 patients were chest pain(n=39,46.4%)and distress(n=27,32.1%).Spearman analysis results revealed a weak positive correlation between FFR-CT and MLA(r=0.49,P<0.0001),while weak negative correlations were found for plaque length,total volume,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume(r=-0.44,-0.56,-0.40,-0.36,-0.42,-0.40;all P<0.05).Additionally,MLD exhibited a moderate negative correlation with FFR-CT(r=-0.60,P<0.0001).In the univariate binary logistic regression analysis,several variables including plaque length,total volume,MLA,MLD,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume were found to be independently associated with FFR-CT≤0.8(All P<0.05).The adjusted multivariate binary logistic regression analysis model revealed that MLD was the sole independent predictor(OR=1.082,95%CI:1.034~1.133,P=0.001).The logistics re-gression model expression was logit(P)=0.079X1-4.052,where X1 represents the value of MLD and achieved a predictive accuracy of 85.2%.The ROC AUC of plaque length,total volume,MLA,MLD,lipid composition vol-ume,fibrous-lipid composition volume,fibrous composition volume and calcified composition volume were 0.796,0.886,0.711,0.754 and 0.698 respectively,and the coresponding sensitivities and specificities were 47.83%,73.91%,73.90%,52.17%,60.87%and 92.11%,73.68%,60.53%,84.21%,89.47%.The five in-dexes combined diagnostic model possessed the largest AUC of 0.906,and 73.91%,71.05%of sensitivity and specificity.Conclusion The AI quantitative parameters of coronary artery plaque exhibited varying degrees of correlation with FFR-CT,while MLD emerged as the sole independent predictor of FFR-CT≤0.8,demonstrating high diagnostic efficiency.

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