1.Network Pharmacology Study of Tongguanteng Injection Inhibits the Proliferation and Migration in Cervical Cancer Cells via Targeting FGF2/MAPK
Dongxu ZHU ; Zhaoying CAI ; Jie XIANG ; Ruoyu ZHOU ; Qiong XU ; Yayun QIAN ; Hongmei LU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):1179-1187
Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.
2.Impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting for osteonecrosis of femoral head
Daoyu ZHU ; Kai FU ; Haiyan HE ; Qianying CAI ; Hao PENG ; Shengbao CHEN ; Jimin YIN ; Pengbo LUO ; Dongxu JIN ; Changqing ZHANG ; Youshui GAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(3):357-364
Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0%in patients without synovitis and 28.5%in those with moderate synovitis,whereas it was significantly higher(60.4%)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95%CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.
3.Network Pharmacology Study of Tongguanteng Injection Inhibits the Proliferation and Migration in Cervical Cancer Cells via Targeting FGF2/MAPK
Dongxu ZHU ; Zhaoying CAI ; Jie XIANG ; Ruoyu ZHOU ; Qiong XU ; Yayun QIAN ; Hongmei LU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(4):1179-1187
Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.
4.Impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting for osteonecrosis of femoral head
Daoyu ZHU ; Kai FU ; Haiyan HE ; Qianying CAI ; Hao PENG ; Shengbao CHEN ; Jimin YIN ; Pengbo LUO ; Dongxu JIN ; Changqing ZHANG ; Youshui GAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(3):357-364
Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0%in patients without synovitis and 28.5%in those with moderate synovitis,whereas it was significantly higher(60.4%)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95%CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.
5.Tryptophan metabolism alters in rotator cuff tear repair in a rat model
Dongxu ZHU ; Xiaohong HUANG ; Xinrui ZHU ; Tengbo YU ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(5):435-443
Objective:To explore whether tryptophan metabolism is related to bone growth by comparing the differences in tryptophan metabolism after rotator cuff tear (RCT) repair between rats with normal bone remodeling capability and those with defective bone remodeling capability.Methods:Of the 50 adult female Sprague Dawley (SD) rats used for this study, 18 were randomly selected to undergo bilateral ovariectomy (OVX) (OVX group), and the remaining 32 underwent bilateral OVX sham surgery (sham surgery group). All rats were maintained in standard conditions. Three months after surgery, 4 rats were randomly selected from OVX group and the sham surgery group, respectively, for Micro CT identification of bone loss at the rat humeral head. The remaining rats in OVX group underwent RCT modeling and surgical repair of acute supraspinatus muscle transection (OVX+RCT group) ( n=14); the remaining rats in the sham surgery group were subjected to either surgical repair of acute supraspinatus muscle transection (RCT group, n=14) or RCT sham surgery (SO group, n=14). The grip power of the rats was tested 2 weeks after surgery. The supraspinatus tendon-bone complex was harvested for evaluation of new bone formation and growth through real-time fluorescence quantitative polymerase chain reaction (qPCR), hematoxylin eosin (HE) staining, and immunohistochemistry (IHC) staining. The tryptophan metabolism was analyzed using ultra high performance liquid chromatography (UPLC). Results:The grip power test showed that SO group had the greatest grip power, followed by RCT group and OVX+RCT group, with statistically significant differences between the 3 groups ( P<0.05). The qPCR showed that the relative expression of osteosclerosis in the tendon-bone complex in SO group was significantly higher than that in OVX+RCT group and RCT group; IHC staining showed that the relative expression of osteocalcin in RCT group was significantly higher than that in SO group and OVX+RCT group ( P<0.05). The UPLC showed that the content of tryptophan in the rotator cuff tendon-bone complex was similar among SO, RCT, and OVX+RCT groups, showing no significant difference ( P>0.05). The qPCR showed that the expression of indoleamine 2, 3-dioxygenase 2 in the Kynurenic acid metabolism pathway showed an increasing trend from SO group to RCT group to OVX+RCT group, with OVX+RCT group significantly higher than SO group ( P<0.05). The expression of 3-hydroxybenzoate 3, 4-dioxygenase in OVX+RCT group was significantly higher than that in RCT group and in SO group ( P<0.001). The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased from SO group to RCT group to OVX+RCT group. The subtypes A and B of monoamine oxidase in the 5-hydroxytryptamine metabolism pathway increased among SO, RCT, and OVX+RCT groups( P<0.001). The expression of dopamine decarboxylase in the indole metabolism pathway in OVX+RCT group was significantly higher than that in SO group ( P<0.01). The expression of cytochrome P450 oxidoreductase increased from SO group to RCT group to OVX+RCT group ( P<0.001). Conclusions:The tryptophan metabolism in the supraspinatus tendon-bone complex after RCT in rats is mainly dominated by kynurenic acid metabolism, followed by 5-hydroxytryptamine metabolism. In RCT bone remodeling, the 5-hydroxytryptamine metabolic pathway changes the most, followed by the indole pathway. The contents of niacin and xanthurenic acid in the kynurenic acid metabolism pathway are related to bone growth; the 5-hydroxytryptamine, hydroxyindoleacetic acid, and melatonin in the 5-hydroxytryptophan metabolic pathway are related to bone growth; the tryptophan and indole lactate in the indole metabolism pathway are related to bone growth. Therefore, tryptophan metabolism is related to bone growth, providing potential therapeutic targets for RCT repair.
6.Postoperative hypoalbuminemia in patients with acute ischemic stroke with successful recanalization by endovascular therapy: risk factors and their impact on outcomes
Hao LU ; Qiang GUO ; Yongnan HAO ; Dongxu YANG ; Ya’nan CHEN ; Zhi ZHU ; Xueyuan LI
International Journal of Cerebrovascular Diseases 2023;31(10):721-727
Objective:To investigate the risk factors of hypoalbuminemia (HA) in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) after endovascular mechanical thromboectomy (EMT) and impact on outcomes.Methods:Patients first diagnosed with anterior circulation LVO-AIS and underwent emergency EMT at the Department of Acute Stroke, the Affiliated Hospital of Jining Medical University from June 1, 2020 to April 31, 2023 were retrospectively included. According to the first follow-up serum albumin examination after procedure (6-8 d), the patients were divided into HA group (<35 g/L) and non-HA group (≥35 g/L). According to the modified Rankin Scale score at 90 d after EMT, the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). Univariate and multivariate logistic analysis was used to determine independent risk factors for HA after EMT and their impact on outcomes. Results:A total of 144 patients were enrolled, including 107 males (74.30%) with a median age of 64 years (interquartile range, 56-71 years). There were 50 patients (34.72%) in the HA group and 94 (65.28%) in the non-HA group; 60 (41.67%) in the good outcome group, and 84 (58.33%) in the poor outcome group. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.061, 95% confidence interval [ CI] 1.014-1.111; P=0.011) and pulmonary infection ( OR 5.136, 95% CI 1.917-13.760; P=0.001) were independent risk factors for HA; HA ( OR 4.345, 95% CI 1.367-13.814; P=0.013), pneumonia ( OR 5.113, 95% CI 1.217-12.528; P=0.026), and onset to reperfusion time ( OR 5.473, 95% CI 1.090-16.05; P=0.038) were independent risk factors for poor outcomes. Conclusions:Age and pulmonary infection are independent risk factors for HA in LVO-ASI patients after EMT, and HA is the independent risk factor for poor outcomes of the patients.
7.Clinical significance of Golgi protein 73 in liver cirrhosis and its relationship with radiological parameters
Jiana LI ; Dongxu WANG ; Yulin HU ; Hongbin ZHU
Chinese Journal of Radiological Health 2022;31(4):512-516
Objective To explore the clinical significance of serum Golgi protein 73 (GP73) in liver cirrhosis and its association with radiological parameters. Methods We included 177 patients with liver cirrhosis and 61 patients with chronic hepatitis admitted to The First Hospital of Jilin University from January 2016 to December 2018, with 70 healthy subjects who underwent physical examination during the same period as the control. We compared GP73, alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), and main portal vein diameter between the patients with liver cirrhosis, patients with chronic hepatitis, and healthy subjects. The GP73 level was further compared between liver cirrhosis subgroups by various classification methods. The correlation between GP73 and ALT, AST, ALB, TBIL, PT, and main portal vein diameter was analyzed. Results The GP73 level was significantly higher in the liver cirrhosis group than in the chronic hepatitis group and the healthy control group (P < 0.001). Patients with decompensated cirrhosis had a significantly higher serum GP73 level than those with compensated cirrhosis (P < 0.001). The serum GP73 levels in the Child-Pugh B and C cirrhosis subgroups were significantly higher than that in the Child-Pugh A cirrhosis subgroup (P < 0.05). In the liver cirrhosis group, the GP73 level was positively correlated with AST, ALT, TBIL, PT, and main portal vein diameter, while negatively correlated with ALB. Conclusion Serum GP73 is significantly increased in patients with liver cirrhosis, which is closely related to liver injury indicators. Serum GP73 shows important clinical value for the early diagnosis and prognosis assessment of liver cirrhosis.
8.Deep vein thrombosis after closed fracture of lower extremity and blood types ABO
Shuhao LI ; Kun ZHANG ; Zhe SONG ; Wei FAN ; Xiaolong WANG ; Chen WANG ; Dongxu FENG ; Lisong HENG ; Fan XU ; Xiao CAI ; Pengfei WANG ; Yangjun ZHU
Chinese Journal of Orthopaedic Trauma 2021;23(1):81-87
Objective:To investigate the differences in incidence of deep vein thrombosis (DVT) after closed fracture of lower extremity between patients with different blood types ABO.Methods:A retrospective study was conducted in the 1, 951 patients who had been admitted to Department of Orthopaedics Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University for lower extremity fractures from August 2014 to June 2018. They were 924 males and 1,027 females with a mean age of 63 (46, 78) years (range, from 16 to 102 years). Of them, 572 were type O, 564 type A, 609 type B and 206 type AB. Venous ultrasonography was performed on both lower extremities within 12 hours after admission. The incidences of DVT after fracture were compared between different blood types in all the patients, patients with proximal fracture of the knee, peri-knee fracture and distal fracture of the knee, and patients<60 years old and ≥60 years old.Results:The incidences of DVT were, respectively, 26.75% (153/572), 28.72% (162/564), 34.32% (209/609) and 29.61% (61/206) for patients with blood type O, type A, type B and type AB. The DVT incidence for type B was significantly higher than that for type O ( P< 0.008). The incidences of DVT were, respectively, 28.74% (98/341), 28.99% (100/345), 39.45% (144/365) and 30.97% (35/113) for blood type O, type A, type B and type AB in the patients with proximal fracture of the knee. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). There were no significant differences in the DVT incidence between different blood types ABO in the patients with peri-knee fracture, distal fracture of the knee,<60 years old or ≥60 years old( P>0.05). The incidences of DVT were, respectively, 30.99% (97/313), 33.33% (108/324), 45.22% (156/345), 34.74% (33/95) for blood type O, type A, type B and type AB in the patients ≥60 years old. The DVT incidence for blood type B was significantly higher than those for blood type O and blood type A ( P< 0.008). Conclusions:The incidence of DVT varied with different blood types ABO after lower extremity fracture. The highest DVT incidence was found in patients with blood type B. The impact of blood type on the DVT incidence after lower extremity fracture was mainly observed in the patients with proximal fracture of the knee or an age of ≥ 60 years old.
9.Association between preoperative hemoglobin amount and incidence of lower limb deep vein thrombosis following lower limb fracture
Shuhao LI ; Kun ZHANG ; Zhe SONG ; Lisong HENG ; Dongxu FENG ; Wei FAN ; Xiaolong WANG ; Chen WANG ; Rui QIAO ; Jiarui YANG ; Pengfei WANG ; Yangjun ZHU
Chinese Journal of Orthopaedic Trauma 2021;23(10):864-870
Objective:To study the association between preoperative hemoglobin amount and incidence of lower limb deep vein thrombosis (DVT) in patients with lower limb fracture.Methods:A retrospective study was performed of the 2, 482 patients with lower limb fracture who had been treated at Department of Orthopaedics Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University from July 2014 to August 2019. They were 1, 174 males and 1, 308 females with an age of (60.6±19.3) years. Recorded were the patients' age, gender, injury time, hemoglobin amount, D-dimer measurement, combined medical conditions, time and results of ultrasound vein examination on both lower extremities. According to the ultrasound results, the patients were divided into a thrombosis group and a thrombosis-free group. The 2 groups were compared in hemoglobin amount. Logistic regression was used to analyze the relationship between preoperative hemoglobin amount and incidence of lower limb DVT. The patients were divided into 5 groups according to the quintile of hemoglobin amount; the incidences of thrombosis were compared between the 5 groups.Results:The total incidence of DVT in this cohort was 29.53%(733/2, 482). The hemoglobin amount in the thrombosis group was (116.57±19.24) g/L, significantly lower than that in the thrombosis-free group (124.76±19.79) g/L ( P<0.05). The preoperative hemoglobin amount was a risk factor for incidence of DVT after a lower limb fracture ( OR=0.985, 95% CI: 0.980 to 0.990, P<0.001). As the quintile level of hemoglobin increased, the incidence of DVT showed a downward trend. In comparison of the group with the highest DVT incidence (40.58%) and the group with the lowest DVT incidence (17.27%), the risk increased by 2.386 times (95% CI: 1.718 to 3.315). Conclusions:The preoperative hemoglobin amount can affect the DVT incidence after a lower limb fracture, and a low hemoglobin amount may more likely lead to lower limb DVT.
10.Screening and Characterization of Effective Components of Immunopotentiating Activity in Senecionis cannabifolii Herba
Tingting ZHOU ; Difu ZHU ; Shengjun JI ; Chunchi WANG ; Dongxu JIA ; Yanru LI ; Yan TANG
China Pharmacy 2019;30(4):523-527
OBJECTIVE: To screen and characterize effective components of immunopotentiating activity in Senecionis cannabifolii Herba. METHODS: The polysaccharide components were obtained by water extraction and alcohol precipitation method to yield 50% alcohol precipitation sample (SCHE-1) and 80% alcohol precipitation sample (SCHE-2). The cells from mice mononuclear macrophage line RAW264.7 were divided into blank group (medium without serum), negative control group (medium with serum), lipopolysaccharide group (LPS, positive control drug, 1 μg/mL), SCHE-1 and SCHE-2 low-dose and high-dose groups (0.5, 1 mg/mL). The cell viability of RAW264.7 cells was detected by MTT assay. The levels of IL-1β, IL-6 and TNF-α in RAW264.7 were detected by ELISA. These were used to investigate the effects of SCHE-1 and SCHE-2 on the immunological enhancing activity of RAW264.7 cells. The molecular weight and distribution of SCHE-1 were determined by size exclusion chromatography; the monosaccharide composition of SCHE-1 was determined by HPLC pre-column derivatization. Methylation analysis of SCHE-1 was conducted by NaOH method. RESULTS: Compared with negative control group, the activity of RAW264.7 cells was enhanced significantly in SCHE-1 groups and LPS group, which also significantly increased the levels of IL-1β, IL-6 and TNF-α in cell culture fluids (P<0.01). SCHE-1 was an effective component with immunopotentiating activity. The neutral sugar content of SCHE-1 was 40.05%, the uronic acid was 35.62%, and the protein was 8.89%. SCHE-1 was a mixture, molecular weight of which was 62-6 119 Da; monosaccharide was mainly composed of galacturonic acid, arabinose (Ara) and galactose (Gal). The results of methylation analysis showed that the backbone was composed of 1→3, 1→4 and 1→6 linked Gal, and branches were on the O-6 position of the 1→3 linked Gal, and the non-reducing terminals were Ara. CONCLUSIONS: SCHE-1 may be the effective component of immuno potentiating activity, and main component of SCHE-1 is polysaccharide. SCHE-1 may regulate the immune function by activating macrophages to release IL-1β, IL-6 and TNF-α.

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