1.Mechanism of Yiqi Huoxue Therapy Regulating IL-33/ST2/IL-1RAP to Improve Nasal Mucosal Tissue Remodeling and Intervene in Allergic Rhinitis
Huan WANG ; Hongping LUO ; Meiya WANG ; Yuyin LIU ; Chenlin WANG ; Chao LIAO ; Fangqi LIANG ; Peizheng XIONG ; Li TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):298-307
ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules (QDYF) alleviate nasal mucosal remodeling in allergic rhinitis (AR) via the interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2)/interleukin-1 receptor accessory protein (IL-1RAP) signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst, according to the previous network pharmacology results, this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways, components, and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently, a rat model of ovalbumin (OVA)-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups: Control, model, low-dose QDYF (QDYF-L, 4.04 g·kg-1), medium-dose QDYF (QDYF-M, 8.08 g·kg-1), high-dose QDYF (QDYF-H, 16.16 g·kg-1), and loratadine (0.9 mg·kg-1). After 14 days of intervention, behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin (HE) staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction (CVF). The expression of E-cadherin (E-cad) in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 (Th2) cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) as well as helper T cell 1 (Th1) cytokines interleukin-2 (IL-2) and interferon-γ (INF-γ) were quantified by enzyme-linked immunosorbent assay (ELISA). The protein levels of transforming growth factor-beta 1 (TGF-β1), IL-33, ST2, and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33, ST2, and IL-1RAP had strong binding ability with the main active ingredients—wogonin, 7-methoxy-2-methylisoflavone, formononetin, naringenin, stigmasterol, and beta-sitosterol of QDYF, with the binding energy < -4.25 kcal⋅mol-1(1 cal≈4.184 J). The results of in vivo experiments showed that compared with the control group, the model group exhibited increased behavioral scores (P<0.05), aggravated pathological damage of nasal mucosa, increased collagen fiber deposition and CVF (P<0.05), elevated serum levels of IL-4, IL-5, and IL-13, up-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05), down-regulated expression of E-cad, and declined serum levels of IL-2, IFN-γ, and IFN-γ/IL-4 ratio (P<0.05). Compared with the model group, the QDYF groups and loratadine group showed reduced behavioral scores (P<0.05), alleviated pathological damage of nasal mucosa, reduced collagen fiber deposition and CVF (P<0.05), and up-regulated E-cad expression (P<0.05). Compared with the model group, the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio (P<0.05), declined serum levels of IL-4, IL-5, and IL-13, and down-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05). In addition, the QDYF-H group exhibited an elevated serum IL-2 level (P<0.05). The QDYF-M group showed down-regulated protein levels of TGF-β1, IL-33 and IL-1RAP in the nasal mucosa (P<0.05). The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa (P<0.05). ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway, thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.
2.Application progress of machine learning in study on cold and hot properties of Chinese materia medica
Jiarou WANG ; Lu ZHOU ; Huimin YUAN ; Yuhan SHENG ; Yaqi ZHANG ; Yang TANG ; Yan SUN ; Fengjie ZHENG ; Yuhang LI
International Journal of Traditional Chinese Medicine 2025;47(3):423-428
The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.
3.A randomized controlled study of deproteinized calf blood extract in the treatment of diabetic cataract with dry eye after phacoemulsification
Fengjie LI ; Can ZHAO ; Li PEI ; Jijun SUN ; Xiaofeng LI ; Mengdi NIU ; Yabin TIAN ; Xiaozhen HE ; Jincong WANG ; Ting WANG
Chinese Journal of Experimental Ophthalmology 2025;43(4):343-349
Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.
4.A randomized controlled study of deproteinized calf blood extract in the treatment of diabetic cataract with dry eye after phacoemulsification
Fengjie LI ; Can ZHAO ; Li PEI ; Jijun SUN ; Xiaofeng LI ; Mengdi NIU ; Yabin TIAN ; Xiaozhen HE ; Jincong WANG ; Ting WANG
Chinese Journal of Experimental Ophthalmology 2025;43(4):343-349
Objective:To compare the clinical effect of deproteinized calf blood extract (DCBE) eye drops and 0.3% sodium hyaluronate eye drops in the treatment of diabetic cataract patients with dry eye after phacoemulsification.Methods:A randomized controlled study was performed.A total of 112 patients (116 eyes) with type Ⅱ diabetes combined with cataract and dry eye who underwent phacoemulsification in the Eye Hospital of Shandong First Medical University from January 2022 to September 2022 were selected.Patients were divided into DCBE group (49 cases, 51 eyes) and sodium hyaluronate group (63 cases, 65 eyes) by the random number table method.Patients received DCBE eye drops and 0.3% sodium hyaluronate eye drops after surgery according to grouping.Preoperative and postoperative 1 week, 1 month subjective symptoms of dry eye, corneal edema grade, tear film breakup time (TBUT), corneal fluorescein staining (CFS) and Schirmer Ⅰ test (SⅠt) results were recorded and compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.SDSYKYY202112-1).Written informed consent was obtained from each subject.Results:There were significant differences in dry eye symptom score, TBUT and SⅠt at different time points between before and after surgery ( Ftime=323.202, 102.771, 151.876; all P<0.001).Dry eye symptom score decreased and SⅠt increased in the two groups at 1 week and 1 month after surgery compared with before surgery, and the differences were statistically significant (all P<0.017).TBUT was longer at 1 week and 1 month after surgery compared with before surgery in the DCBE group, and TBUT at 1 month after surgery was longer than that before surgery in the sodium hyaluronate group, and the differences were statistically significant (all P<0.017).There were statistically significant differences in CFS scores between the two groups at different time points before and after surgery ( Fgroup=5.391, P=0.022; Ftime=142.402, P<0.001).The CFS scores of both groups at 1 week and 1 month after surgery were lower than those before surgery, and CFS scores in the DCBE group were lower than those in the sodium hyaluronate group, with statistically significant differences (all P<0.017).One week after surgery, the proportion of patients with corneal edema in the DCBE group was 5.9%(3/51), which was significantly lower than 20.0%(13/65) in the sodium hyaluronate group ( χ2=4.790, P=0.029). Conclusions:DCBE eye drops can promote corneal repair, stabilize tear film and improve dry eye discomfort in early postoperative period in diabetic cataract, and its overall effect is better than 0.3% sodium hyaluronate eye drops.
5.Mechanism of Compound Fufangteng Mixture in improving isoproterenol-induced myocardial fibrosis by regulating HSPA8
Fengjie ZHOU ; Yafang CHEN ; Jianlong NAN ; Yuhong LI ; Jun HE ; Han ZHANG ; Wei LEI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1081-1094
Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.
6.Managing atopic dermatitis through the perspectives of"clear-turbid interference"and the"gut-skin axis"
Shengxuan ZHAO ; Yang TANG ; Rongxin LI ; Wantong CUI ; Fengjie ZHENG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1413-1418
Atopic dermatitis is a common chronic,relapsing,inflammatory skin disease;however,its pathogenesis remains unclear.The theory of"clear-turbid interference"originates from the Inner Canon of Yellow Emperor and refers to a pathological condition in which clear yang and turbid yin intermingle,and qi movement becomes disordered.This paper elucidates the theoretical connotation of"clear-turbid interference"and its core mechanism in triggering atopic dermatitis,as well as the role of the"gut-skin axis"in atopic dermatitis development.Internal dampness-turbidity and disharmony between ying and wei constitute the core pathological mechanisms linking clear-turbid interference to atopic dermatitis.Treatment for different stages and syndromes should be guided by syndrome differentiation.For example,for spleen deficiency with a dampness syndrome in subacute or chronic stages,Chushi Weiling Decoction may be used to fortify the spleen,eliminate dampness,lift the clear,and downbear the turbid.For patterns with prominent heat manifestations,such as dampness-heat immersion or heart fire with spleen deficiency,bitter-cold dampness-drying herbs can be added on this basis.For wind-dampness-heat accumulation in the acute stage,Mahuang Lianyao Chixiaodou Decoction can be used to release the exterior,expel pathogens,and harmonize ying and wei.In cases of spleen deficiency with blood dryness or liver-kidney insufficiency during the chronic stage,in addition to nourishing yin to moisten the skin and tonifying the liver-kidney,wind-medicinals should also be employed to open the sweat pores and promote qi movement.These approaches restore the physiological state without clear-turbid interference while regulating intestinal flora,providing new approaches and perspectives for integrating traditional Chinese and Western medicine in treating atopic dermatitis.
7.Managing atopic dermatitis through the perspectives of"clear-turbid interference"and the"gut-skin axis"
Shengxuan ZHAO ; Yang TANG ; Rongxin LI ; Wantong CUI ; Fengjie ZHENG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1413-1418
Atopic dermatitis is a common chronic,relapsing,inflammatory skin disease;however,its pathogenesis remains unclear.The theory of"clear-turbid interference"originates from the Inner Canon of Yellow Emperor and refers to a pathological condition in which clear yang and turbid yin intermingle,and qi movement becomes disordered.This paper elucidates the theoretical connotation of"clear-turbid interference"and its core mechanism in triggering atopic dermatitis,as well as the role of the"gut-skin axis"in atopic dermatitis development.Internal dampness-turbidity and disharmony between ying and wei constitute the core pathological mechanisms linking clear-turbid interference to atopic dermatitis.Treatment for different stages and syndromes should be guided by syndrome differentiation.For example,for spleen deficiency with a dampness syndrome in subacute or chronic stages,Chushi Weiling Decoction may be used to fortify the spleen,eliminate dampness,lift the clear,and downbear the turbid.For patterns with prominent heat manifestations,such as dampness-heat immersion or heart fire with spleen deficiency,bitter-cold dampness-drying herbs can be added on this basis.For wind-dampness-heat accumulation in the acute stage,Mahuang Lianyao Chixiaodou Decoction can be used to release the exterior,expel pathogens,and harmonize ying and wei.In cases of spleen deficiency with blood dryness or liver-kidney insufficiency during the chronic stage,in addition to nourishing yin to moisten the skin and tonifying the liver-kidney,wind-medicinals should also be employed to open the sweat pores and promote qi movement.These approaches restore the physiological state without clear-turbid interference while regulating intestinal flora,providing new approaches and perspectives for integrating traditional Chinese and Western medicine in treating atopic dermatitis.
8.Mechanism of Compound Fufangteng Mixture in improving isoproterenol-induced myocardial fibrosis by regulating HSPA8
Fengjie ZHOU ; Yafang CHEN ; Jianlong NAN ; Yuhong LI ; Jun HE ; Han ZHANG ; Wei LEI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1081-1094
Objective This study aims to evaluate the therapeutic efficacy of Compound Fufangteng Mixture(CFM)on myocardial fibrosis(MF)and explore its action targets and mechanisms through a combination of animal pharmacodynamics,cell biology,and network pharmacology approaches.Methods Thirty-five male C57BL/6J mice were divided into the normal group,model group,CFM low-dose(0.72 g/kg)group,CFM high-dose(1.44 g/kg)group,and sacubitril valsartan sodium group(20 mg/kg)based on random number table,with 7 mice in each group.Except for the normal group,the mice in the other groups were subcutaneously injected with isoproterenol(20 mg/kg)at multiple points once daily for 21 consecutive days to establish the MF model.The CFM groups were pre-administered by gavage 3 days before modeling,the sacubitril valsartan sodium group was administered starting from the day of modeling,and the normal group and model group were given an equal volume of distilled water.The active ingredients in CFM were analyzed using ultra-performance liquid chromatography(UPLC).On days 7,14,and 21 of modeling,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVIDd),and left ventricular end-systolic diameter(LVIDs)of mice were detected by ultrasound.The degree of myocardial fibrosis in mice was assessed by Masson staining.The levels of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),type I collagen(COL I),and type Ⅲcollagen(COL Ⅲ)in the myocardial tissue of mice were detected by enzyme-linked immunosorbent assay(ELISA).The average fluorescence intensity of α-SMA in myocardial tissue was detected by immunofluorescence.In addition,by integrating Cellular Thermal Shift Assay(CETSA),QE proteomic analysis,and network pharmacology techniques,we systematically explored the potential core targets and mechanisms of action by which CFM improves MF,and validated these findings using western blotting analysis.Results Main eight chemical components were identified from CFM.Compared with the normal group,the model group exhibited a decrease in LVEF and LVFS,an increase in LVIDd and LVIDs,a higher heart weight to tibia length ratio,and an increased collagen volume fraction(P<0.05),along with aggravated MF.Concurrently,the myocardial tissue showed elevated levels of TGF-β1,α-SMA,COL I,and COL Ⅲ(P<0.05),with enhanced α-SMA fluorescence signal intensity.In comparison to the model group,all groups of CFM and the sacubitril valsartan sodium group demonstrated an increase in LVEF and LVFS,and a decrease in LVIDd,LVIDs,and the heart weight to tibia length ratio(P<0.05).Simultaneously,the collagen volume fraction decreased,and the levels of TGF-β1,α-SMA,COL I,and COL Ⅲ in myocardial tissue were down-regulated(P<0.05).The degree of MF was reduced,and the fluorescence signal intensity of α-SMA expression was weakened.Furthermore,the combined analysis of CETSA,QE proteomics,and network pharmacology revealed that heat shock protein A family member 8(HSPA8)may be a potential core target for CFM in ameliorating MF.CETSA-western blotting analysis further confirmed that CFM could enhance the thermal stability of HSPA8 protein and down-regulate the relative expression level of HSPA8 protein in mouse myocardial tissue(P<0.05).Conclusion CFM can ameliorate isoproterenol-induced cardiac dysfunction in mice,reduce collagen deposition,and reverse the pathological progression of MF.The underlying mechanism may be associated with the regulation of HSPA8.
9.Short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure
MENG Maolong ; Yao WANG ; Pingfan LU ; Huapeng LI ; Rong REN ; Wen ZHANG ; Fengjie CHEN ; Xianmian ZHUANG ; Xiang WANG ; Gang LI ; Hongwei GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):283-287
Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P<0.001), and between half a year after surgery and before discharge after surgery (P<0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.
10.Correlation of interferon-induced gene IFIT1 with immune infiltration and prognosis in ovarian cancer
Ruiwei WANG ; Fengjie LI ; Xiaolong LIANG ; Xin ZHOU ; Liping LIU ; Qiurong LI ; Mingmin HE ; Yudi LI
Journal of Army Medical University 2024;46(10):1132-1141
Objective To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1(IFIT1)with immune infiltration and prognosis of ovarian cancer(OC).Methods GEO database was employed to select the tumor immune related genes,and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis.The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA,Human Protein Atlas,and Timer databases.The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database.In addition,based on David database,GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases.Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually.Finally,after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA,the tumor growth was observed in the transplanted nude mice,and infiltration of neutrophils was observed with immunohistochemical assay.Results FIT1,a tumor immune gene,selected from the GEO database,Kaplan-Meier and Prognoscan databases,was negatively correlated with the OC prognosis.GEPIA,Human Protein Atlas,Timer database,and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues,and had no obvious correlation with tumor stage and grade.Analysis in String,Genemania,and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5'oligonucleotide synthase,virus defense,and innate immunity,and other processes.The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8+T cells,B cells,dendritic cells,neutrophils,and macrophage in OC,with neutrophils having the most significant correlation.Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC(P<0.05).RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice(P<0.05)and reduced neutrophil infiltration in the xenograft tissues.Conclusion IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.

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