1.Fufang Changtai Decoction Inhibites Colorectal Cancer Through Ferroptosis:Investigation of the Underlying Mechanism
Jialin GU ; Lingchang LI ; Ming LIU ; Shan DENG ; Jialin YU ; Jiege HUO ; Yi JI
Journal of Sichuan University (Medical Sciences) 2025;56(3):647-655
Objective To investigate the underlying mechanisms of the effect of Fufang Changtai Decoction(FFCT)in inhibiting colorectal cancer(CRC)through the ferroptosis pathway using network pharmacology combined with experimental validation.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Swiss Target Prediction databases were employed for the systematic screening of potent active ingredients and therapeutic targets of FFCT.In addition,the identification of CRC-associated genes and ferroptosis-related genes(FRGs)was accomplished using the Gene Cards and FerrDb databases,respectively.Venn diagrams,coupled with Cytoscape software,facilitated the comprehensive analysis of key FRGs involved in FFCT's intervention in CRC by mapping the TCM compound-therapeutic target network.Transmission electron microscopy was used to examine the mitochondrial ultrastructure of SW480 and HCT116,2 Human CRC cell lines,after treatment with FFCT-containing serum.Intracellular reactive oxygen species(ROS)levels were measured using a ROS detection kit.To assess the role of ferroptosis,ferroptosis inhibitor liproxstatin-1(Lip-1)was co-administered with FFCT-containing serum.The effects on cancer cell viability and proliferation were evaluated using CCK-8 and colony formation assays.Key molecular targets involved in the regulatory effects of FFCT on the expression of FRGs were further analyzed using PCR Array and Western blot.The findings were then validated with human CRC tissue microarrays.Results A total of 103 active ingredients of FFCT,739 therapeutic targets,9 101 disease-related genes,and 564 FRGs were identified.Venn diagram analysis identified 81 FRGs associated with FFCT intervention.Network analysis revealed that NQO1,TP53,and PTGS2 served as hub nodes in the regulatory network.Findings from the in vitro experiments showed that FFCT induced ferroptosis changes,including mitochondrial condensation,membrane thickening,and cristae reduction,in SW480 and HCT116 cells.FFCT treatment significantly increased intracellular ROS levels in a dose-dependent manner(P<0.05)and reduced cancer cell viability and proliferative capacity(P<0.01).These inhibitory effects were partially reversed by Lip-1,suggesting that FFCT's antitumor activity was closely associated with the ferroptosis pathway.PCR Array and Western blot analyses further confirmed that FFCT significantly downregulated NQO1 mRNA and protein expression in cancer cells(P<0.001),which was consistent with network pharmacology predictions.Immunofluorescence analysis of clinical CRC tissue microarrays revealed that NQO1 expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.001).Conclusion FFCT may induce intracellular ferroptosis by downregulating the oncogenic gene NQO1,thereby exerting anti-CRC effects.
2.Characteristics and risk factors of postoperative lower extremity deep vein thrombosis in patients with lumbar degenerative diseases
Bo-Lin SUN ; Xu XIONG ; Yan-Xin ZHONG ; Yu LIU ; Liu-Xue DU ; Teng-Hui TAO ; Shan-Hu HUANG ; Zhi-Li LIU ; Jia-Ming LIU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1117-1121
Objective To analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.
3.Construction of a lentiviral cell line with overexpression of human HACE1 and its impact on the proliferation and migration of glioma cells
Ran Huang ; Ming Shan ; Weisong Li
Acta Universitatis Medicinalis Anhui 2025;60(7):1241-1245
Objective :
To construct a lentiviral overexpression cell line of HACE1 and to investigate its effects on the proliferation and migration of glioma cells.
Methods :
Using the bacterial liquid containing the full-length cDNA sequence of human HACE1 as a template,the lentiviral expression plasmid pCDH-HACE1 was constructed,and the lentiviral cell line was screened.Western blot was employed to detect the expression of HACE1 in glioma cells. Meanwhile,the CCK-8 assay and the cell scratch assay were utilized to assess the impacts of HACE1 on the prolif- eration and migration of glioma cells.
Results :
The lentiviral cell line with HACE1 overexpression was successfully established.Western blot analysis demonstrated that HACE1 could be effectively expressed in eukaryotic cells.The results of the CCK-8 assay showed that,compared with the control group,the cell proliferation in the HACE1 over- expression group was significantly enhanced at 24 hours and 48 hours after cultivation (both P<0. 01) .The cell scratch assay revealed that,at 24 hours and 48 hours after cultivation,the Scratch areas in the HACE1 overexpres- sion group were higher than those in the control group (P<0. 05,P<0. 01) .
Conclusion
The lentiviral cell line with HACE1 overexpression is successfully constructed.HACE1 can promote the proliferation and migration abili- ties of U251 glioma cells,providing a foundation for further research.
4.Construction of a lentiviral cell line with overexpression of human HACE1 and its impact on the proliferation and migration of glioma cells
Ran Huang ; Ming Shan ; Weisong Li
Acta Universitatis Medicinalis Anhui 2025;60(7):1241-1245
Objective :
To construct a lentiviral overexpression cell line of HACE1 and to investigate its effects on the proliferation and migration of glioma cells.
Methods :
Using the bacterial liquid containing the full-length cDNA sequence of human HACE1 as a template,the lentiviral expression plasmid pCDH-HACE1 was constructed,and the lentiviral cell line was screened.Western blot was employed to detect the expression of HACE1 in glioma cells. Meanwhile,the CCK-8 assay and the cell scratch assay were utilized to assess the impacts of HACE1 on the prolif- eration and migration of glioma cells.
Results :
The lentiviral cell line with HACE1 overexpression was successfully established.Western blot analysis demonstrated that HACE1 could be effectively expressed in eukaryotic cells.The results of the CCK-8 assay showed that,compared with the control group,the cell proliferation in the HACE1 over- expression group was significantly enhanced at 24 hours and 48 hours after cultivation (both P<0. 01) .The cell scratch assay revealed that,at 24 hours and 48 hours after cultivation,the Scratch areas in the HACE1 overexpres- sion group were higher than those in the control group (P<0. 05,P<0. 01) .
Conclusion
The lentiviral cell line with HACE1 overexpression is successfully constructed.HACE1 can promote the proliferation and migration abili- ties of U251 glioma cells,providing a foundation for further research.
5.Malignancy risk assessment and cause analysis of the Bethesda class Ⅰ/Ⅲ cytolo-gy diagnosis due to insufficient cell volume in thyroid solid nodule
Hongzhen YU ; Ming LI ; Xiang XIE ; Xiaofeng LAN ; Tianyu XU ; Shan HUANG ; Xian WANG ; Zhenzhong FENG
Chinese Journal of Clinical and Experimental Pathology 2025;41(1):44-50
Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3%and a ROM of 38.5%,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5%and a ROM of 59.4%.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4%,67.6%)were higher than those of C-TIRADS ≤4a(12.7%,39.8%),and the differences were statistically significant(P<0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter<5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,<0.001,<0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,<0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.
7.Support vector machine model based on gray matter volume for identifying amyotrophic lateral sclerosis and analysis of relevant brain regions
Shan WU ; Haining LI ; Qiuli ZHANG ; Qianqian DUAN ; Xinyi YU ; Xing QIN ; Fangfang HU ; Jiaoting JIN ; Jingxia DANG ; Ming ZHANG
Chinese Journal of Medical Imaging Technology 2025;41(7):1051-1055
Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10%was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40%GMV features had the highest classification accuracy(82.50%),with sensitivity,specificity and area under the curve(AUG)of 85.05%,80.40%and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.
8.Research progress on role of necroptosis in chronic kidney disease
Ping QIU ; Shuo HUANG ; Qi-han LUO ; Qing MA ; Fu-zhe CHEN ; Zi-yi SHAN ; Yi-ming LIU ; Chang-yu LI
Chinese Pharmacological Bulletin 2025;41(5):816-820
Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.
9.Clinical Analysis of Cutaneous Chronic Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation in Childhood.
Yu-Xian WANG ; Hao XIONG ; Zhi CHEN ; Li YANG ; Fang TAO ; Yu DU ; Zhuo WANG ; Ming SUN ; Shan-Shan QI ; Lin-Lin LUO
Journal of Experimental Hematology 2025;33(5):1461-1467
OBJECTIVE:
To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.
METHODS:
A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed.
RESULTS:
During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections.
CONCLUSION
The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans
;
Graft vs Host Disease/etiology*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Retrospective Studies
;
Risk Factors
;
Female
;
Child
;
Skin Diseases/etiology*
;
Chronic Disease
;
Transplantation, Homologous
;
Male
;
Child, Preschool
;
Adolescent
10.PI-RADS v2.1 score combined with PSA density for diagnosis of clinically significant prostate cancer in the PSA grey zone by MRI-TRUS cognitivefusion-guided transperineal targeted prostate biopsy.
Yue LI ; Shan ZHOU ; Jing CHEN ; Fei MAO ; Xiao-Bing NIU ; Li SUN ; Ming XU ; Jin-Tao LIU
National Journal of Andrology 2025;31(1):50-54
OBJECTIVE:
To assess the value of the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) score combined with PSA density (PSAD) in the diagnosis of clinically significant prostate cancer (CSPCa) in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy.
METHODS:
This retrospective study included 327 male patients with total PSA (tPSA) levels of 4-10 μg/L undergoing MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy in our hospital between January 2021 and December 2023. According to the pathological results, we divided the patients into a CSPCa (n = 44) and a non-CSPCa group (n = 283), collected their clinical and imaging data, and subjected them to statistical analysis.
RESULTS:
The age, tPSA level, PSAD and PI-RADS score were significantly higher, while the free PSA (fPSA) level, f/tPSA ratio and prostate volume remarkably lower in the CSPCa than in the non-CSPCa group (P<0.05). The areas under the curve (AUCs) of PSAD, PI-RADS score and their combination were 0.772, 0.730 and 0.801, with sensitivities of 63.63%, 70.45% and 72.73%, and specificities of 84.10%, 75.62% and 83.75%, respectively (P<0.01). With PSAD 0.2 μg/(ml·cm3) as the best cut-off value and based on the PI-RADS scores, the patients were divided into two groups for analysis. In the patients with PI-RADS scores 2 and 5, the AUCs were 0.534 and 0.643, with sensitivities of 16.67% and 63.64%, and specificities of 85.14% and 64.29%, with no statistically significant differences (P= 0.784, P= 0.228), and in those with PI-RADS scores 3 and 4, the AUCs were 0.794 and 0.843, with sensitivities of 57.14% and 80.00%, and specificities of 87.14% and 81.82%, with statistically significant differences (P= 0.009, P<0.001).
CONCLUSION
PI-RADS v2.1 score combined with PSAD can effectively improve the diagnostic efficiency of CSPCa in the PSA grey zone by MRI-TRUS cognitive fusion-guided transperineal targeted prostate biopsy and serve as a guide for selection of prostate biopsy.
Humans
;
Male
;
Prostatic Neoplasms/diagnostic imaging*
;
Retrospective Studies
;
Prostate-Specific Antigen
;
Magnetic Resonance Imaging
;
Image-Guided Biopsy
;
Prostate/pathology*
;
Aged
;
Middle Aged


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