OBJECTIVE To compare the risk of pneumonitis and interstitial lung disease （ILD） associated with different antibody-drug conjugates （ADC） in the treatment of breast cancer. METHODS CNKI， VIP， PubMed， Embase and other Chinese and English databases， and ClinicalTrials.gov were searched from the inception to June 15， 2025. Randomized controlled trials （RCT） about pneumonitis and ILD associated with ADC （T-DM1， T-DXd， SG， Dato-DXd， SHR-A1811，ARX788， and T-Duo） in the treatment of breast cancer were included. After literature screening， data extraction， and quality assessment， a network meta-analysis was conducted using Stata 17.0 software， and the surface under the cumulative ranking curve（SUCRA） of all interventions were ranked. RESULTS A total of 19 RCTs involving 10 556 patients were included. The overall incidence of pneumonitis with ARX788 and T-DXd was significantly higher than that with T-DM1， T-DM1 plus TPC（T-DM1combined with pertuzumab or atezolizumab）， TPC（treatment of primary care）， and SG （ P ＜0.05）， for grade 1-2 pneumonitis， ARX788 and T-DXd showed significantly higher incidence than T-DM1， T-DM1 plus TPC， and TPC （ P ＜0.05）. For both indicators， ARX788 and T-Duo were ranked as the top two by SUCRA. For the incidence of grade ≥3 pneumonitis， T-DXd and T-DM1 were significantly higher than SG （ P ＜0.05）， T-Duo and Dato-DXd were ranked as the top two by SUCRA. For overall incidence of ILD， ARX788 was significantly higher than T-DM1， SHR-A1811， TPC， and SG （ P ＜0.05）， for the incidence of grade 1-2 ILD， ARX788 was significantly higher than T-DM1， SHR-A1811， and TPC （ P ＜0.05）， for the incidence of grade ≥3 ILD， ARX788 was significantly higher than TPC （ P ＜0.05）. For three indicators above， ARX788 and T-DXd combined with pertuzumab were ranked as the top two by SUCRA. CONCLUSIONS Compared with other ADCs， ARX788 and T-Duo are associated with a higher risk of pneumonitis and ILD in patients with breast cancer.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective To observe the value of ultrasound radiomics based on convolutional neural network(CNN)for predicting effect of neoadjuvant chemotherapy(NAC)for breast cancer.Methods Totally 164 women with breast cancer were retrospectively enrolled and divided into effective group(n=68)and ineffective group(n=96)according to the treatment response,also randomly divided into training set(n=131)and validation set(n=33)at the ratio of 8∶2.Based on ultrasound before NAC,radiomics features of breast cancer were extracted and screened with CNN,radiomics models were constructed with logistic regression(LR),support vector machine(SVM),K-nearest neighbor(KNN),random forest(RF)and multilayer perceptron(MLP),respectively.The best radiomics model was selected,deep learning score(DL-Score)was calculated,and the nomogram was drawn combined with clinical features.Results Among 5 radiomics models,MLP model had the best comprehensive efficacy for predicting effect of NAC for breast cancer,and its sensitivity,specificity and area under the curve(AUC)in training set was 77.78％,92.21％and 0.929,respectively,which in validation set was 78.57％,84.21％and 0.921,respectively.The estrogen or progesterone receptor,human epidermal growth factor receptor 2 and DL-Score were all independent predictors of NAC effect for breast cancer(all P＜0.05).The sensitivity,specificity and AUC of nomogram drawn based on the above independent predictors was 83.30％,92.21％and 0.953 in training set,85.71％,94.74％and 0.955 in validation set,respectively.AUC of the nomogram was slightly higher than that of MLP model,but no significant difference was found(both P＞0.05).The integrated discrimination improvement index showed that adding clinical features(i.e.the above-mentioned immunohistochemically indicators)could improve the predictive performance of radiomics models(P＜0.001).Conclusion Ultrasound radiomics based on CNN could be used to predict effect of NAC for breast cancer.Combining with immunohistochemically indicators might improve their efficacy.

Objective:To investigate the role of iron death in paraquat (PQ) -induced alveolar epithelial mesangialization (EMT) .Methods:In August 2023, the appropriate PQ staining concentration as well as the intervention concentration of lipoinhibitor-1 (Lip-1) were screened by CCK8 method. The RLE-6TN cells were divided into three groups, which were control group, PQ group and iron death inhibition group, 200 μmol/L PQ solution was given to the PQ group, and PQ 200 μmol/L and 0.1 μmol/L Lip-1 solution was given to the iron death inhibition group, the control group was added the same amount of cell medium. morphological changes and migratory viability of the cells in each group were observed at 12 h, 24 h and 48 h after the poisoning, and the contents of ferrous ions (Fe 2+), reactive oxygen radicals (ROS), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected in each group; meanwhile, qRT-PCR and western-blot were used to determine the molecular expression of E-cadherin, α-smooth muscle actin (α-SMA), and Collagen I in the cells in each group. The difference between group was compared by ANOVA, and the further pairwise comparison was conducted by Bonferroni method. Results:Cell viability was detected using CCK8, and the results showed that the cell survival rate of RLE-6TN cells treated with 200 μmol/L PQ+0.1 μmol/L Lip-1 solution was 56.6%. The migration activity of RLE-6TN cells in the iron death inhibition group was weaker than that in the PQ group after 24 and 48 hours of exposure, and the degree of EMT changes in the cells was reduced compared to the PQ group. After 12, 24, and 48 hours of exposure, the Fe 2+ concentration, ROS fluorescence intensity, and MDA content in the iron death inhibition group decreased compared to the corresponding time points in the PQ group ( P<0.05/3), while compared with PQ group, the GSH concentration and SOD concentration increased compared to the corresponding time points in the PQ group ( P<0.05/3). The results showed that compared with the control group, the expression levels of E-cadherin mRNA and protein in PQ group and iron death inhibition group were both decreased ( P<0.05/3), while compared with PQ group, the expression levels of E-cadherin mRNA and protein in iron death inhibition group were increased ( P<0.05/3) ; Compared with the control group, the expression levels of α-SMA, Collagen I mRNA and protein in PQ group and iron death inhibition group cells increased ( P<0.05/3), while compared with PQ group, the expression levels of α-SMA, Collagen I mRNA and protein in iron death inhibition group cells decreased ( P<0.05/3) . Conclusion:Ferroptosis is involved in the EMT process of alveolar epithelial cells induced by PQ. Inhibiting ferroptosis can reduce cellular oxidative damage and alleviate the degree of cellular EMT.

Objective To observe the value of ultrasound radiomics based on convolutional neural network(CNN)for predicting effect of neoadjuvant chemotherapy(NAC)for breast cancer.Methods Totally 164 women with breast cancer were retrospectively enrolled and divided into effective group(n=68)and ineffective group(n=96)according to the treatment response,also randomly divided into training set(n=131)and validation set(n=33)at the ratio of 8∶2.Based on ultrasound before NAC,radiomics features of breast cancer were extracted and screened with CNN,radiomics models were constructed with logistic regression(LR),support vector machine(SVM),K-nearest neighbor(KNN),random forest(RF)and multilayer perceptron(MLP),respectively.The best radiomics model was selected,deep learning score(DL-Score)was calculated,and the nomogram was drawn combined with clinical features.Results Among 5 radiomics models,MLP model had the best comprehensive efficacy for predicting effect of NAC for breast cancer,and its sensitivity,specificity and area under the curve(AUC)in training set was 77.78％,92.21％and 0.929,respectively,which in validation set was 78.57％,84.21％and 0.921,respectively.The estrogen or progesterone receptor,human epidermal growth factor receptor 2 and DL-Score were all independent predictors of NAC effect for breast cancer(all P＜0.05).The sensitivity,specificity and AUC of nomogram drawn based on the above independent predictors was 83.30％,92.21％and 0.953 in training set,85.71％,94.74％and 0.955 in validation set,respectively.AUC of the nomogram was slightly higher than that of MLP model,but no significant difference was found(both P＞0.05).The integrated discrimination improvement index showed that adding clinical features(i.e.the above-mentioned immunohistochemically indicators)could improve the predictive performance of radiomics models(P＜0.001).Conclusion Ultrasound radiomics based on CNN could be used to predict effect of NAC for breast cancer.Combining with immunohistochemically indicators might improve their efficacy.

Objective:To investigate the role of iron death in paraquat (PQ) -induced alveolar epithelial mesangialization (EMT) .Methods:In August 2023, the appropriate PQ staining concentration as well as the intervention concentration of lipoinhibitor-1 (Lip-1) were screened by CCK8 method. The RLE-6TN cells were divided into three groups, which were control group, PQ group and iron death inhibition group, 200 μmol/L PQ solution was given to the PQ group, and PQ 200 μmol/L and 0.1 μmol/L Lip-1 solution was given to the iron death inhibition group, the control group was added the same amount of cell medium. morphological changes and migratory viability of the cells in each group were observed at 12 h, 24 h and 48 h after the poisoning, and the contents of ferrous ions (Fe 2+), reactive oxygen radicals (ROS), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected in each group; meanwhile, qRT-PCR and western-blot were used to determine the molecular expression of E-cadherin, α-smooth muscle actin (α-SMA), and Collagen I in the cells in each group. The difference between group was compared by ANOVA, and the further pairwise comparison was conducted by Bonferroni method. Results:Cell viability was detected using CCK8, and the results showed that the cell survival rate of RLE-6TN cells treated with 200 μmol/L PQ+0.1 μmol/L Lip-1 solution was 56.6%. The migration activity of RLE-6TN cells in the iron death inhibition group was weaker than that in the PQ group after 24 and 48 hours of exposure, and the degree of EMT changes in the cells was reduced compared to the PQ group. After 12, 24, and 48 hours of exposure, the Fe 2+ concentration, ROS fluorescence intensity, and MDA content in the iron death inhibition group decreased compared to the corresponding time points in the PQ group ( P<0.05/3), while compared with PQ group, the GSH concentration and SOD concentration increased compared to the corresponding time points in the PQ group ( P<0.05/3). The results showed that compared with the control group, the expression levels of E-cadherin mRNA and protein in PQ group and iron death inhibition group were both decreased ( P<0.05/3), while compared with PQ group, the expression levels of E-cadherin mRNA and protein in iron death inhibition group were increased ( P<0.05/3) ; Compared with the control group, the expression levels of α-SMA, Collagen I mRNA and protein in PQ group and iron death inhibition group cells increased ( P<0.05/3), while compared with PQ group, the expression levels of α-SMA, Collagen I mRNA and protein in iron death inhibition group cells decreased ( P<0.05/3) . Conclusion:Ferroptosis is involved in the EMT process of alveolar epithelial cells induced by PQ. Inhibiting ferroptosis can reduce cellular oxidative damage and alleviate the degree of cellular EMT.

OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

Objective:To investigate the role of connective tissue growth factor (CTGF) and PI3K/Akt signaling pathways in paraquat (PQ) -induced alterations in alveolar epithelial cell mesenchymalization (EMT) .Methods:In February 2023, RLE-6TN cells were divided into 2 groups, which were set as uncontaminated group and contaminated group (200 μmol/L PQ), and cellular EMT alteration, CTGF and PI3K/Akt signaling pathway related molecules expression were detected by cell scratch assay, qRT-PCR and western-blot assay. Using shRNA interference technology to specifically inhibit the expression of CTGF, RLE-6TN cells were divided into four groups: control group, PQ group (200 μmol/L PQ), interference group (transfected with a plasmid with shRNA-CTGF+200 μmol/L PQ), and null-loaded group (transfected with a plasmid with scramble- CTGF+200 μmol/L PQ), qRT-PCR and western blot were used to examine the alteration of the cellular EMT and the expression of molecules related to the activity of PI3K/Akt pathway. The PI3K/Akt signaling pathway was blocked by the PI3K inhibitor LY294002, and the expression of EMT-related molecules in cells of the control group, PQ group (200 μmol/L PQ), and inhibitor group (200 μmol/L PQ+20 μmol/L LY294002) was examined by qRT-PCR and western blot.The t-test was used to compare the differences between the two groups, while the analysis of variance (ANOVA) was applied to compare the differences among multiple groups. For further pairwise comparisons, the Bonferroni method was adopted.Results:The results of cell scratch test showed that compared with the uncontaminated group, RLE-6TN cells in the contaminated group had faster migration rate, lower mRNA and protein expression levels of E-Cadherin, and higher mRNA and protein expression levels of α-SMA, CTGF, PI3K and Akt, with statistical significance ( P<0.05). After specific inhibition of CTGF expression, the mRNA and protein expression of CTGF, PI3K, Akt, and α-SMA in the cells of the interference group were significantly lower than that of the PQ group and the null-loaded group ( P<0.05/6), whereas that of E-Cadherin was higher than that of the PQ group and the null-loaded group ( P<0.05/6). Specifically blocking the PI3K/Akt signaling pathway, the mRNA and protein expression of PI3K, Akt and α-SMA in the cells of the inhibitor group was decreased compared with that of the PQ group ( P<0.05/3), while the expression of E-Cadherin was elevated compared with that of the PQ group ( P<0.05/3) . Conclusion:CTGF may promote PQ-induced alveolar epithelial cell EMT through activation of the PI3K/Akt signaling pathway. Inhibition of CTGF expression or blockade of PI3K/Akt signaling pathway activity can alleviate the extent of PQ-induced alveolar epithelial cell EMT.

Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo-lar epithelial interstitial transformation(EMT)and its related signaling pathways.Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad),alpha-smooth muscle actin(α-SMA)and Collagen I(Col I)in the process of EMT induced by TGF-β1.LncSIL interacting proteins were ana-lyzed by RNA pulldown.Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2)and its downstream factors P21 and cyclin-de-pendent kinase 6(CDK6).Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression.Re-sults After lncSIL silencing,the expression of α-SMA and Col I increased,the expression of E-cad decreased.RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL,and the expression of EZH2 increased after silencing lncSIL,the expression of EZH2 downstream gene P21 decreased,CDK6 increased.Flow cytometry showed that the number of cells in S phase significantly increased.When lncSIL was overexpressed,the expression of EZH2 and CDK6 was down-regulated,the expression of P21 was up-regulated,and the number of S phase cells significantly decreased.Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen-chymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.