1.Feiyanning Inhibits Invasion and Metastasis of Non-small Cell Lung Cancer by Regulating EMT via TGF-β1/Smad Signaling Pathway
Xiaojie FU ; Jia YANG ; Kaile LIU ; Wenjie WANG ; Zhenye XU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):110-120
ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition (EMT) and invasion and metastasis of non-small cell lung cancer (NSCLC). MethodsCell proliferation and activity were assessed using the cell counting kit-8(CCK-8) assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β1 was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β1-induced NSCLC cell metastasis, EMT, and the TGF-β1/Smad pathway proteins were assessed by wound healing assay, Transwell assay, and Western blot. In vivo, an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups: Model (NC) group, Feiyanning low-dose (FYN1) group, Feiyanning high-dose (FYN2) group, and the positive control group (TGF-β receptor kinase inhibitor SB431542 group). The corresponding interventions were performed. After 40 days, the mice were euthanized, and lung metastases were analyzed. The expression of E-cadherin, N-cadherin, p-Smad2, and p-Smad3 in each group was detected by immunohistochemistry (IHC). ResultsAfter Feiyanning intervention, compared to the blank group, Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner (P<0.01). The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group (P<0.01). The expression of EMT marker proteins N-cadherin and zinc finger transcription factors (Zeb1, Snail, Slug) was significantly reduced in the Feiyanning groups compared to the blank group (P<0.05, P<0.01). The expression of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ, key proteins in the TGF-β1/Smad signaling pathway, was also significantly decreased (P<0.01). In the TGF-β1-induced EMT model, compared to the TGF-β1 group, the cell metastasis ability in the Feiyanning groups was reduced (P<0.01), and the expression levels of N-cadherin, Zeb1, Snail, and Slug were significantly lower (P<0.01). The expression levels of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ were also significantly reduced (P<0.01). In vivo results showed that compared to the model group, the number of lung metastases in the FYN1, FYN2, and SB431542 groups was reduced (P<0.01), and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group, the expression of E-cadherin in the FYN1, FYN2, and SB431542 groups was increased (P<0.01), the expression of N-cadherin decreased (P<0.05, P<0.01), and the expression of p-Smad2 and p-Smad3, key proteins of the TGF-β1/Smad pathway, was reduced (P<0.01). ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β1/Smad signaling pathway.
2.Feiyanning Inhibits Invasion and Metastasis of Non-small Cell Lung Cancer by Regulating EMT via TGF-β1/Smad Signaling Pathway
Xiaojie FU ; Jia YANG ; Kaile LIU ; Wenjie WANG ; Zhenye XU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):110-120
ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition (EMT) and invasion and metastasis of non-small cell lung cancer (NSCLC). MethodsCell proliferation and activity were assessed using the cell counting kit-8(CCK-8) assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β1 was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β1-induced NSCLC cell metastasis, EMT, and the TGF-β1/Smad pathway proteins were assessed by wound healing assay, Transwell assay, and Western blot. In vivo, an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups: Model (NC) group, Feiyanning low-dose (FYN1) group, Feiyanning high-dose (FYN2) group, and the positive control group (TGF-β receptor kinase inhibitor SB431542 group). The corresponding interventions were performed. After 40 days, the mice were euthanized, and lung metastases were analyzed. The expression of E-cadherin, N-cadherin, p-Smad2, and p-Smad3 in each group was detected by immunohistochemistry (IHC). ResultsAfter Feiyanning intervention, compared to the blank group, Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner (P<0.01). The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group (P<0.01). The expression of EMT marker proteins N-cadherin and zinc finger transcription factors (Zeb1, Snail, Slug) was significantly reduced in the Feiyanning groups compared to the blank group (P<0.05, P<0.01). The expression of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ, key proteins in the TGF-β1/Smad signaling pathway, was also significantly decreased (P<0.01). In the TGF-β1-induced EMT model, compared to the TGF-β1 group, the cell metastasis ability in the Feiyanning groups was reduced (P<0.01), and the expression levels of N-cadherin, Zeb1, Snail, and Slug were significantly lower (P<0.01). The expression levels of p-Smad2/3, Smad2/3, TβRI, and TβRⅡ were also significantly reduced (P<0.01). In vivo results showed that compared to the model group, the number of lung metastases in the FYN1, FYN2, and SB431542 groups was reduced (P<0.01), and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group, the expression of E-cadherin in the FYN1, FYN2, and SB431542 groups was increased (P<0.01), the expression of N-cadherin decreased (P<0.05, P<0.01), and the expression of p-Smad2 and p-Smad3, key proteins of the TGF-β1/Smad pathway, was reduced (P<0.01). ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β1/Smad signaling pathway.
3.Research Progress in Treatment of Malignant Tumors by Traditional Chinese Medicine Based on Exosomes
Cancer Research on Prevention and Treatment 2024;51(2):80-84
Malignant tumor is still one of the malignant diseases with high morbidity and mortality in the world. Its occurrence and development are influenced by various factors. Exosomes are nanoscale secretory vesicles that play an important role in the occurrence and development of malignant tumors, and have intercellular communication functions. The mechanism of action of traditional Chinese medicine in prevention and treatment of tumors is not yet comprehensive enough. This article discusses the relationship between exosomes and tumor development, relapse, metastasis and drug resistance, and the application of exosomes in the treatment of malignant tumors by traditional Chinese medicine, to provide reference for finding new breakthroughs in the treatment of malignant tumors.
4.The value of radiomics combined with deep learning based on preoperative CT images in predicting the curative effect of transarterial chemoembolization for hepatocellular carcinoma
Dandan WANG ; Haibo WANG ; Zhongqi SUN ; Huijie JIANG
Chinese Journal of Radiology 2024;58(2):209-215
Objective:To explore the value of radiomics and deep learning in predicting the efficacy of initial transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods:This was a cohort study. The imaging and clinical information of HCC patients treated with TACE in the Second Affiliated Hospital of Harbin Medical University from January 2015 to January 2021 were collected retrospectively. A total of 265 patients were divided into response group (175 cases) and non-response group (90 cases) according to the modified solid tumor efficacy evaluation criteria (mRECIST) 1 to 2 months after initial TACE. According to the proportion of 8∶2, the patients were randomly divided into training group (212 cases, 140 responders and 72 non-responders) and test set (53 cases, 35 responders and 18 non-responders). Univariate and multivariate logistic regression was used to screen clinical variables and construct a clinical model. The radiomics features were extracted from the preoperative CT images, and radiomics model was constructed after feature dimensionality reduction. Using the deep learning method, three residual network (ResNet) models (ResNet18, ResNet50 and ResNet101) were established, and their effectiveness was compared and integrated to build a deep learning model with best performance. Univariate and multivariate logistic regression was used to combine pairwise three models to establish the combined model. The receiver operating characteristic curve was used to evaluate the performance of the model to distinguish between TACE response and non-response groups.Results:In the test set, the area under the curve (AUC) of the clinical model and the radiomics model in the differentiation between response and non-response after TACE were 0.730 (95% CI 0.569-0.891) and 0.775 (95% CI 0.642-0.907). The AUC of ResNet18, ResNet50 and ResNet101 were 0.719, 0.748 and 0.533, respectively. The AUC for deep learning model obtained by integrating ResNet18 and ResNet50 was 0.806 (95% CI 0.665-0.946). After pairwise fusion, the combined deep learning-radiomics model showed the highest performance, with an AUC of 0.843 (95% CI 0.730-0.956), which was better than those of the deep learning-clinical model (AUC of 0.838, 95% CI 0.719-0.957) and the radiomics-clinical model (AUC of 0.786, 95% CI 0.648-0.898). Conclusions:The combined model of radiomics and deep learning has high performance in predicting the curative effect of TACE in patients with HCC before operation.
5.Isopsoralen accelerates tibia fracture healing by promoting bone formation in mice
Xi WU ; Zhongqi WANG ; Yuhai GAO ; Zhenlong WEI ; Xin BAI ; Keming CHEN
Journal of Army Medical University 2024;46(3):240-248
Objective To determine the effect of isopsoralen(ISO)on the healing of tibia fracture in mice and explore its underlying mechanism.Methods Fifty male C57BL/6 mice(2 month old,20±2 g)were randomly divided into model group and ISO treatment group,with 25 animals in each group.From the 3rd day after modeling,the mice from the ISO group were given an intragastric gavage of 40 mg/kg ISO,once per day for 28 consecutive days,while those of the model group was given same volume of normal saline in same way.On the 7th,14th,21st,and 28th day after gavage,the tibia on the surgical side was taken,and the fracture area was quantified by bone volume/total volume(BV/TV)after micro-CT scanning.The healing and shaping of the fracture end were observed through HE staining.ELISA was used to detect the serum contents of bone alkaline phosphatase(BALP)and procollagen type I N-terminal peptide(PINP)on the 14th day of gavage.Western blotting was employed to determine the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX,and VEGF in the tibial callus tissue in 7 and 14 d after gavage.Vascular perfusion was applied to observe the callus microvessels in 28 d to quantitatively analyze the vascular volume fraction and vessel diameter.Immunohistochemical staining was conducted to observe the expression of VEGF in the callus in 14 d after gavage.Results HE staining displayed that the ISO group had faster healing process than the model group.Micro-CT quantification results showed that the ISO group had higher BV/TV ratio in 7 d after gavage though no statistical difference,significantly higher ratio in 14 d(P<0.05),but obviously lower ratio in 21 and 28 d after gavage(both P<0.05)when compared with the model group.The serum contents of BALP and PINP were also remarkably higher in the ISO group than the model group(P<0.05).Western blotting results indicated that the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX and VEGF in the ISO group were higher than those in the model group(P<0.05).The results of angiography revealed that the vascular volume fraction and vessel diameter were notably increased in the ISO group than the model group(both P<0.05).Immunohistochemical assay showed that the expression of VEGF was higher in the ISO group than the model group(P<0.05).Conclusion ISO can improve the activity of osteoblasts,increase the expression of osteogenesis-related proteins,and accelerate the angiogenesis to promote fracture healing.
6.The current situation of willingness to receive prophylactic treatment among students with latent tuberculosis infection and its influencing factors in Jiangsu Province
WANG Zhan ; LI Zhongqi ; DING Xiaoyan ; LU Peng ; ZHU Limei ; LIU Qiao ; LU Wei
China Tropical Medicine 2024;24(3):244-
Objective To assess the willingness of students with latent tuberculosis infection (LTBI) in Jiangsu Province to undergo preventive treatment and identify factors influencing their decision, aiming to provide insights for tuberculosis prevention and control strategies in school. Methods The physical examination information of tuberculosis latent infection cases was collected from screenings of new school enrollment and contacts of tuberculosis patients in 6 cities of Jiangsu Province from December 2022 to December 2023. Data on past medical history and understanding of preventive treatment were gathered through an online questionnaire survey on the website of Juanxing, and the influencing factors related to the willingness to take preventive medication were analyzed by logistic regression analysis model. Results In December 2022 to December 2023, a total of 13 school tuberculosis outbreaks occurred in 6 cities, and 1 661 contacts were screened, among which 162 cases met the criteria for prophylactic medication, 96 cases were included in the study by filling in the questionnaire. A total of 22 600 new students from 56 schools participated in the TB screening upon enrollment, of which 358 tested positive for the tuberculin skin test alone, meeting the criteria for preventive medication, and 251 of them completed the willingness survey. Finally, 347 students who met the criteria for preventive treatment were included in the study, with 164 expressing to accept preventive treatment representing a treatment acceptance rate of 47.3%. The results of multivariate analysis showed that university (OR=17.950, 95%CI: 3.078-104.686, P=0.001) and contact with the source of school tuberculosis epidemic (OR=19.542, 95%CI: 6.289-60.726, P<0.001) were associated with increased willingness to receive preventive treatment, while unclear whether to pay for the drugs themselves (OR=0.349, 95%CI:0.133-0.916, P=0.032) was associated with decreased willingness to receive preventive treatment. Compared with Huai'an City, the willingness to receive preventive treatment was significantly lower among students from Nantong City (OR=0.005, 95%CI:0.000-0.063, P<0.001), Nanjing City (OR=0.022, 95%CI: 0.003-0.703, P<0.001) and Lianyungang City (OR=0.074, 95%CI:0.008-0.703, P=0.023). Conclusions The acceptance rate of preventive treatment among LTBI students in Jiangsu Province is not high and is affected by multiple factors. Health education and medication mobilization for preventive medication are essential.
7.Clinical features of and influencing factors of obsessive-compulsive personality disorder in patients with obsessive-compulsive disorder
Wenjing JIANG ; Xuhui WANG ; Zhihan XU ; Xuedi ZHANG ; Zhongqi WANG ; Ping ZHOU ; Na LIU
Sichuan Mental Health 2024;37(4):317-322
Background Obsessive-compulsive personality disorder and obsessive-compulsive disorder(OCD)are common psychological disorders with similar clinical symptoms,but the differences between the two need further clarification.Objective To explore the clinical features of and influencing factors of obsessive-compulsive personality disorder in patients with OCD,so as to provide references for further relevant clinical diagnosis and treatment.Methods A total of 195 patients with OCD were selected as the research subjects,who received treatment at the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University from July 2022 to December 2023 and met the diagnostic criteria for OCD in the International Classification of Diseases,tenth edition(ICD-10).Evaluation was conducted by using the Yale-Brown Obsessive Compulsive Scale(Y-BOCS),Personality Diagnostic Questionnaire-4+(PDQ-4+),Obsessive-Compulsive Inventory-Revised(OCI-R),Beck Depression Inventory(BDI),Beck Anxiety Inventory(BAI)and Sheehan Disability Scale(SDS).In accordance with the score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4+,patients were divided into the OCD group with obsessive-compulsive personality disorder(n=58)and the OCD group without obsessive-compulsive personality disorder(n=137).Pearson correlation analysis and Spearman correlation analysis were adopted to examine the correlation between clinical features and the score of the Obsessive-Compulsive Personality Disorder Scale.Multiple linear regression analysis was used to explore the influencing factors of OCD patients with obsessive-compulsive personality disorder.Results Statistically significant differences were observed between OCD patients with and without obsessive-compulsive personality disorder in the age,family history of mental illness,time without treatment,hoarding and ranking dimension scores in OCI-R,OCI-R total score,score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4,and BDI score(P≤0.05).OCD patients with obsessive-compulsive personality disorder in the time without treatment,OCI-R total score,hoarding and ranking dimension scores in OCI-R and BDI score are all positively correlated with the score of the Obsessive-Compulsive Personality Disorder Scale(r=0.120,0.526,0.364,0.492,0.414,P<0.05).The results of multiple linear regression analysis showed that time without treatment(β=0.132,P<0.05),hoarding dimension score(β=0.283,P<0.05)and ranking dimension score in OCI-R(β=0.418,P<0.05)were the influencing factors of OCD patients with obsessive-compulsive personality disorder.Conclusion OCD patients with obsessive-compulsive personality disorder may have longer untreated periods,more pronounced functional impairments in hoarding and sorting and more severe depressive symptoms.Untreated time,hoarding symptoms and sorting symptoms may be influencing factors for OCD patients with obsessive-compulsive personality disorder.
8.Effect of modified toe-spread-out exercises in female patients with hallux valgus
Lianfu DIAO ; Zhicheng ZHOU ; Mengting LIU ; Liang ZHANG ; Zhongqi YU ; Yao YU ; Chao WANG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(12):1473-1478
ObjectiveTo compare the effect of toe-spread-out exercises (TSO) and modified TSO in females with hallux valgus. MethodsFrom September to December, 2023, a total of 45 females with hallux valgus were recruited in Capital University of Physical Education and Sports and randomly divided into blank control group (n = 15), TSO group (n = 15), and modified TSO group (n = 15). The blank control group received no intervention, the TSO group received routine TSO, and the modified TSO group received fibularis longus fascia release followed by TSO, for eight weeks. Changes in the hallux valgus angle (HVA) and the cross-sectional area (CSA) of the abductor hallucis muscle were measured before intervention, and four and eight weeks after intervention, respectively. ResultsOne case dropped out from the blank control group. The changes of HVA in the TSO and modified TSO groups were significantly greater than in the blank control group (F > 15.263, P < 0.05). After four weeks of intervention, the change of left HVA in the modified TSO group was significantly greater than in the TSO group (P < 0.05). The main effect of time was significant on the CSA of the abductor hallucis muscle (F > 13.245, P < 0.05). The main effect of group was significant on the left foot's CSA of the abductor hallucis (F = 3.798, P < 0.05). The interaction effect of time and group was also significant (F > 4.744, P < 0.05). The CSA of the abductor hallucis in both the TSO and modified TSO groups after four weeks and eight weeks of intervention was significantly greater than before intervention (P < 0.05). At eight weeks, the CSA of the right foot in the modified TSO group was significantly greater than in the blank control group (P < 0.05). ConclusionBoth TSO and modified TSO can improve HVA and the CSA of the abductor hallucis muscle in females with hallux valgus, and modified TSO is better.
9.Automatic segmentation of identified vertebral bones from CT images using CA-SegResNet
Zhongqi ZHU ; Xiaolong GAO ; Yinghao LI ; Guang YANG ; Liguo HAO ; Hongzhi WANG
Chinese Journal of Medical Physics 2024;41(11):1349-1356
A three-dimensional(3D)medical image segmentation network(CA-SegResNet)which incorporates a 3D coordinate attention mechanism is proposed to address the issue of segmenting identified vertebral bones from spinal computed tomography(CT)images.The network extracts image features through a deep residual convolutional neural network and fuses the feature maps from each encoder layer with the input of the corresponding decoder layer.Subsequently,a 3D coordinate attention module is introduced to capture inter-channel relationships as well as directional and positional information,establishing long-range dependencies across different spatial directions,thereby enabling precise segmentation of the identified vertebral bones.For the segmentation tasks involving the identified cervical vertebra(the 7th cervical vertebra)and the identified thoracic vertebra(the 12th thoracic vertebra)across 105 cases,CA-SegResNet achieves average Dice similarity coefficients(DSC)of 0.934 5 and 0.918 9 on the test set,with average Hausdorff distances(HD)of 7 and 8 mm.Compared with U-Net results,the average DSC is improved by 0.014 5 and 0.0463,while average HD is reduced by 176 and 388 mm.The results demonstrate that the network can realize the precise segmentation of identified vertebral bones from CT images.
10.Evaluation of the efficacy of QuantiFERON-TB Gold Plus screening for latent tuberculosis infection in the prison population
FEI Xinru ; WANG Zhan ; LI Zhongqi
China Tropical Medicine 2024;24(7):807-
Abstract: Objective To evaluate the performance of QuantiFERON-TB Gold Plus (QFT-Plus) in screening the prison population for latent tuberculosis infection (LTBI), and analyze the related influencing factors of latent infection, so as to provide the basis for screening the prison population for latent tuberculosis infection. Methods The basic characteristics and screening results of the newly admitted prison population were collected, using QuantiFERON-TB Gold (QFT-GIT) assay as the gold standard. The kappa value and the area under the ROC curve were used to evaluate the detection performance of QFT-Plus. At the same time, Kruskal-Wallis test was used to compare the difference of IFN-γ production between tubes. A logistic regression model was established to analyze the influencing factors of latent tuberculosis infection in the prison population. Results A total of 100 valid subjects were included in this study, and 24 LTBI patients were screened. The median age of the participants was 38 years, with a median LTBI age of 44 years and a median healthy age of 37 years. In addition, the education level was mainly concentrated in college and above. Consistency checks of various screening methods revealed that the highest coincidence rate of QFT-Plus and QFT-GIT detection results was 0.917, with the largest area under the curve at 0.958. The K-W analysis showed that the amount of IFN-γ in QFT-Plus TB tube was significantly higher than that in QFT-GIT TB tube, and the variation range of IFN-γ in QFT-Plus tube was greater. In addition, multivariate analysis showed that increasing age (aOR: 1.046, 95%CI: 1.004-1.089) was a risk factor for LTBI in the prison population, while having an education level of college or above (aOR: 0.263, 95%CI: 0.071-0.972) was a protective factor. Conclusions QFT-Plus, as a newly developed method for detecting LTBI, showed basic consistency with QFT-GIT, and the consistency was higher than that of other skin test methods. However, due to the large variation of IFN-γ production in QFT-Plus, it is still necessary to further explore the diagnostic threshold. In the screening of LTBI in prisons, special attention should be given to the elderly population and the population with low education levels.

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