1.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
2.Nomogram model based on multiparametric MRI combined with clinical features in identifying benign and malignant BI-RADS 4 lesions
Han ZHOU ; Wan TANG ; Zhiheng LI ; Xiaoyan CHEN ; Yao FU ; Renhua WU ; Yan LIN
Chinese Journal of Radiology 2024;58(4):388-393
Objective:To investigate the efficacy of the nomogram model based on multiparametric MRI combined with clinical features for differential diagnosis of benign and malignant breast imaging reporting and data system (BI-RADS) 4 lesions.Methods:This study was a cross-sectional study. Clinical and imaging data of 56 patients (66 lesions) with pathologically confirmed BI-RADS 4 breast lesions from January 2020 to June 2022 at Second Affiliated Hospital of Shantou University Medical College were retrospectively analyzed. The patients were all females aged 42 (17, 71) years old. All patients underwent the breast MRI, including T 1WI, T 2WI, diffusion-weighted imaging, diffusion kurtosis imaging (DKI), and dynamic-enhanced MRI (DCE-MRI), and the patient clinical characteristics, imaging characteristics as well as relevant MRI quantitative parameters were recorded. Comparisons of the indicators of benign and malignant BI-RADS 4 lesions were performed by sample t-test , Mann-Whitney U, or χ 2 test. The least absolute shrinkage and selection operator regression was utilized to further select indicators with statistically significant differences in univariate analyses, and finally, nomogram models were constructed and reclassified all the lesions. Results:Of the 66 lesions in 56 patients, 24 lesions were found in 24 malignant patients and 42 lesions in 32 benign patients. The differences in age, body mass index, and menopausal status between benign and malignant patients were statistically significant (all P<0.05); the differences in tumor longest diameter, type of lesion enhancement, time-single intensity curve type, mean diffusivity and mean kurtosis (MK) between benign and malignant lesions were statistically significant (all P<0.05). After feature selection, MK ( OR=27.952, 95% CI 1.301-600.348, P=0.033), age ( OR=1.140, 95%CI 1.040-1.249, P=0.005), and the type of lesion enhancement ( OR=0.045, 95%CI 0.006-0.316, P=0.005) were the independent influences in predicting BI-RADS 4 malignant lesions. Using this to construct a nomogram model, its area under the curve for predicting BI-RADS 4 malignant lesions was 0.946, and the accuracy of reclassifying 66 BI-RADS 4 lesions as benign versus malignant was 86.36% (57/66). Conclusion:The nomogram model constructed with MK from DKI parameters, the type of lesion enhancement from DCE-MRI, and age is valuable in diagnosing the benign and malignant nature of BI-RADS 4 lesions.
3.TCM constitution distribution and clinical features of patients with hepatitis B cirrhosis and dysplastic nodules
Mengbing FANG ; Cheng LIU ; Yu ZHANG ; Jiayi ZENG ; Zhiheng CHEN ; Sheng LI ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2024;40(5):961-967
Objective To investigate the characteristics of TCM constitution distribution in hepatitis B cirrhosis patients with dysplastic nodules(DN),and to provide a basis for the prevention and treatment of precancerous lesions of liver cancer.Methods This study was conducted among 113 hepatitis B cirrhosis patients with DN,105 hepatitis B cirrhosis patients with regenerative nodules(RN),and 70 hepatitis B cirrhosis patients with small hepatocellular carcinoma(sHCC)who were hospitalized in Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2015 to March 2023.Related data were collected,including age,sex,liver function Child-Pugh class,TCM constitution type,and laboratory markers.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups;the chi-square test was used for comparison of categorical data between groups,and the Bonferroni correction method was used for further comparison between two groups.Results The main TCM constitution types of hepatitis B cirrhosis patients with DN were Qi-deficiency constitution(27 patients,23.89%),blood-stasis constitution(26 patients,23.01%),and phlegm-dampness constitution(23 patients,20.35%).There were significant differences between the three groups in the proportion of patients with phlegm-dampness constitution or damp-heat constitution(χ2=6.822 and 6.383,both P<0.05);the hepatitis B cirrhosis patients with RN had the highest proportion of patients with phlegm-dampness constitution(30.48%),followed by those with DN(20.35%)and those with sHCC(14.29%),while the hepatitis B cirrhosis patients with sHCC had the highest proportion of patients with damp-heat constitution(27.14%),followed by those with DN(16.81%)and those with RN(12.38%).There were significant differences between the hepatitis B cirrhosis DN patients with different TCM constitution types in sex,age,Child-Pugh class,prealbumin,albumin(Alb),aspartate aminotransferase,total bilirubin(TBil),total bile acid,and alpha-fetoprotein(all P<0.05).Compared with the male hepatitis B cirrhosis DN patients,female patients showed a significantly higher proportion of patients with Qi-deficiency constitution(χ2=4.895,P=0.027).Among the patients with Qi-deficiency constitution,the patients with Child-Pugh class A liver function accounted for a significantly lower proportion than those with Child-Pugh class B liver function(χ2=6.380,P=0.012),while among the patients with phlegm-dampness constitution,the patients with Child-Pugh class A liver function accounted for a significantly higher proportion than those with Child-Pugh class B liver function(χ2=8.515,P=0.004).The patients with phlegm-dampness constitution had significantly higher levels of prealbumin and Alb than those with the other four constitutions(all P<0.05),as well as significantly lower levels of TBil and total bile acid than those with damp-heat constitution(P<0.05);the patients with Yin-deficiency constitution had a significantly lower level of Alb than those with qi-deficiency constitution,blood-stasis constitution,or phlegm-dampness constitution(all P<0.05);the patients with Yin-deficiency constitution had a significantly lower proportion of patients with abnormal alpha-fetoprotein than those with non-Yin-deficiency constitutions(χ2=4.448,P=0.035).Conclusion Hepatitis B cirrhosis patients with DN mainly have the TCM constitution types of Qi deficiency,blood stasis,and phlegm dampness.The patients with phlegm-dampness constitution seem to have a low probability of carcinogenesis,while those with damp-heat constitution and Yin-deficiency constitution have a relatively high risk of carcinogenesis.
4.Prediction of different expression status of human epidermal growth factor receptor 2 in breast cancer based on multi-parameter MRI habitat imaging
Zhiheng LI ; Xiaoyan CHEN ; Xiaolei ZHANG ; Han ZHOU ; Yao FU ; Renhua WU ; Yan LIN
Chinese Journal of Radiology 2024;58(9):909-915
Objective:To investigate the value of multi-parameter MRI habitat imaging in differentiating human epidermal growth factor receptor 2 (HER2) expression in breast cancer.Methods:This study was cross-sectional. A retrospective analysis was conducted on the clinical and imaging data of 86 cases of primary invasive breast cancer confirmed by pathology at the Second Affiliated Hospital of Shantou University from August 2018 to July 2023. All patients were female, aged 33 to 74 (51±10) years. All patients underwent breast MRI examinations, including T 1WI, T 2WI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. The fuzzy C-means clustering algorithm was applied to cluster analysis of the volume ratio of the extracellular extravascular space (V e), the rate constant (K ep), the volume transfer constant (K trans), and the apparent diffusion coefficient (ADC) for all lesions. Different habitat subregions were segmented based on breast cancer. Blood perfusion of the lesion was quantified through mean values of K trans and K ep, and cell proliferation was evaluated by the mean values of ADC and V e in each subregion. Additionally, the percentage of each subregion′s volume in relation to the total lesion volume was calculated. The Mann-Whitney U test was used to compare the differences in the volume percentages of various habitat subregions between different HER2 expression status. The diagnostic performance of statistically significant parameters in determining HER2 status was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:Among the 86 patients with invasive breast cancer, 27 were HER2 positive and 59 were HER2 negative. Among the HER2 negative patients, 37 had low and 22 had zero HER2 expression. The volume percentages of habitat subregions 1, 2, and 3 showed statistically significant differences between HER2 positive and HER2 negative patients ( Z=2.90, P=0.004; Z=-2.04, P=0.042; Z=-2.19, P=0.029), with AUC values of 0.696, 0.638, and 0.648, respectively, for predicting HER2 positive expression. The volume percentage of habitat subregion 2 showed a statistically significant difference between low and zero HER2 expression patients ( Z=2.85, P=0.004), with an AUC value of 0.724 for predicting low versus zero HER2 expression. Conclusions:The volume percentage of habitat subregion 1 effectively distinguishes HER2 status, and the volume percentage of habitat subregion 2 effectively distinguishes between low and zero HER2 expression patients. It has significant clinical implications for identifying potential candidates for HER2-targeted therapy.
5.Over the top reconstruction combined with modified Lemaire technique in the treatment of anterior cruciate ligament injury with pivot-shift positive
Xianxiang XIANG ; Ruixin LI ; Jia LIU ; Zhiheng WEI ; Jue GONG ; Chunhui LI ; Wanqing QI ; Mengyang JIA ; Weiyi CHEN ; Ying YANG ; Weiming WANG
Chinese Journal of Orthopaedics 2024;44(7):438-446
Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.
6.A national multi-center prospective study on the perioperative practice of enhanced recovery after surgery for choledochal cysts in children
Ming YUE ; Jiexiong FENG ; Yan′an LI ; Yuanmei LIU ; Zhigang GAO ; Qi CHEN ; Hongwei XI ; Qiang YIN ; Chengji ZHAO ; Yuzuo BAI ; Wanfu LI ; Libin ZHU ; Weibing TANG ; Hongqiang BIAN ; Huizhong NIU ; Zhiheng GUO ; Heying YANG
Chinese Journal of General Surgery 2024;39(11):827-832
Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.
7.Expression of miR-204 and SIRT1 in colorectal cancer and their clinical significance
Liyong HUANG ; Jiaming WU ; Yuping PENG ; Jin LI ; Zhiheng CHEN
China Modern Doctor 2024;62(22):58-62
Objective To investigate the expression of miR-204 and silence information regulator 1(SIRT1)in colorectal cancer and their clinical value.Methods Cancer tissue specimens and paracancer tissue specimens of 60 patients with colorectal cancer treated in Department of Gastrointestinal Surgery of Affiliated Hospital of Jiaxing University from May 2018 to June 2020 were collected as study objects.Real time fluorogenic quantitative polymerase chain reaction was used to detect the gene expression of miR-204 and SIRT1,and the correlation between miR-204 and SIRT1 gene expression was compared by Pearson analysis.Immunohistochemical SABC method was used to detect SIRT1 protein expression,and relationship between different SIRT1 protein expression and clinicopathological features was compared.Kaplan-Meier method was used to analyze the survival difference of colorectal cancer patients with different SIRT1 protein expression.Results The mRNA expression of miR-204 gene in cancer tissues was significantly lower than that in paracancer tissues(P<0.05),and the mRNA expression of SIRT1 gene was significantly higher than that in paracancer tissues(P<0.05).Pearson correlation analysis showed that miR-204 was negatively correlated with SIRT1 mRNA expression in both paracancer tissues and cancer tissues(r=-0.647,-0.737,P<0.05).The expression of SIRT1 protein was correlated with the differentiation level,invasion level,lymph node metastasis and TNM stage of colorectal cancer(P<0.05),but not with patient age,gender,tumor size and tumor site(P>0.05).Kaplan-Meier analysis showed that the survival rate of patients with positive expression of SIRT1 in cancer tissues was significantly lower than that of patients with negative expression of SIRT1(χ2=5.001,P=0.025).Conclusion The expression of miR-204 is down-regulated and SIRT1 expression is up-regulated in colorectal cancer tissues,which may jointly promote the metastasis and invasion of colorectal cancer and affect the prognosis of patients through mutual influence.
8.Validity and reliability of the Chinese version of children’s trust in general nurses scale
Qingqing CHONG ; Dan CHEN ; Zhiheng ZHAN ; Jing CHEN ; Enfang SHAN ; Xianwen LI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(11):1032-1037
Objective:To translate the Children's trust in general nurses scale (CTGNS) into Chinese, and conduct item response theory (IRT) analysis and reliability and validity evaluation.Methods:Following Brislin's translation model, the CTGNS was translated, back-translated, and cross-culturally adapted to form the Chinese version of the CTGNS.A total of 502 pediatric inpatients from a pediatric hospital in Nanjing city were surveyed from July to August 2022.The Samejima graded response model in IRT was used to calculate the difficulty and discrimination parameters of each item, while item characteristic curves were plotted.The reliability and validity of the Chinese version CTGNS were evaluated.SPSS 26.0, Mplus 8.0 and MULTILOG 7.03 softwares were used for data analysis.Results:The item discrimination of the Chinese version CTGNS ranged from 0.088 to 2.730.The difficulty parameters ranged from -4.667 to 26.094 and increased with increasing difficulty levels without any reverse thresholds.The item characteristic curves exhibited sound shapes for all items except for item 9.Based on the selection criteria of the corresponding parameters, 8 items were retained.The revised Chinese version CTGNS (8 items) consisted of 3 dimensions.The content validity index (CVI) of each item ranged from 0.833 to 1.000, and the total scale CVI was 0.960.The Cronbach's α coefficient for the overall scale was 0.822, and the Cronbach's α coefficients for each dimension ranged from 0.752 to 0.852.The test-retest reliability of the scale was 0.87.Exploratory factor analysis yielded 3 common factors with a cumulative variance contribution rate of 73.468%.Confirmatory factor analysis indicated a good model fit( χ2/ df=2.674, RMSEA=0.082, SRMR=0.046, CFI=0.964). Conclusion:The revised Chinese version CTGNS demonstrates sound reliability and validity and can be used as an assessment tool for measuring children's trust in nurses.
9.Shoulder arthroscopic balance point compaction with cross suture-bridge technique for treatment of avulsion fracture of the greater tuberosity of the humerus
Xianxiang XIANG ; Ruixin LI ; Jia LIU ; Jue GONG ; Zhiheng WEI ; Chunhui LI ; Mengyang JIA ; Weiyi CHEN ; Ying YANG ; Weiming WANG
Chinese Journal of Trauma 2023;39(11):999-1005
Objective:To investigate the efficacy of shoulder arthroscopic balance point compaction with cross suture-bridge technique inr the treatment of avulsion fracture of the greater tuberosity of the humerus.Methods:A retrospective case series study was conducted on 14 patients with avulsion fracture of the greater tuberosity of the humerus treated in Affiliated Xinhua Hospital of Dalian University from March 2021 to March 2022, including 8 males and 6 females; aged 30-58 years [(40.2±10.5)years]. Among them, 5 patients had fracture in the left shoulder and 9 in the right shoulder. The fracture was classified as the avulsion type according to Mutch classification. All the patients were treated with shoulder arthroscopic balance point compaction with cross suture-bridge technique. The anteroposterior X-ray of the shoulder joint was taken at 1 week, 3 months, and 6 months after surgery to evaluate fracture reduction and fixation. The operative time and intraoperative blood loss were recorded. Fracture healing was evaluated by shoulder MRI at 6 months after surgery. The visual analog score (VAS), Constant shoulder joint score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (active abduction angle, active lateral external rotation angle, and active lateral internal rotation) preoperatively, at 3, 6 months after surgery and at the last follow-up were compared. The postoperative complications were observed.Results:All the patients were followed up for 12-15 months [(12.5±0.8)months]. The operative time and intraoperative blood loss were (67.0±10.5)minutes and (20.0±3.8)ml. The anteroposterior X-ray of the shoulder joint showed good reduction and fixation at 1 week, 3 months and 6 months after surgery. MRI T1 image at 6 months after surgery showed locally evenly distributed high signal, suggesting that the fracture was healed well. The values of VAS were (3.2±0.4)points, (2.5±0.5)points, and (0.7±0.3)points at 3, 6 months after surgery and at the last follow-up, which were lower than (7.2±0.6)points preoperatively; the values of Constant joint shoulder score were (53.2±5.3)points, (81.1±4.4)points, and (92.8±5.3)points, which were higher than (42.3±7.6)points preoperatively; the values of ASES score were (55.6±3.6)points, (77.1±3.2)points, and (90.8±3.5)points, which were higher than (45.8±4.2)points preoperatively; the active abduction angles were (60.5±2.5)°, (107.8±6.6)°, and (168.5±3.5)°, which were higher than (18.3±3.3)°preoperatively; the active lateral external rotation angles were (25.8±2.5)°, (30.8±2.2)°, and (63.8±2.8)°, which were higher than (15.6±3.2)°preoperatively ( P<0.05 or 0.01). The level of active internal rotation was L 5, L 1, and T 10, which was better than S 3 before surgery. The VAS, Constant shoulder joint score, ASES score, active abduction and active external rotation were significantly improved at the last follow-up compared with those at 3, 6 months after surgery (all P<0.05), with markedly improved level of active internal rotation. No major complications such as infection, instability of the shoulder joint or acromial impingement were found after surgery. Conclusion:Shoulder arthroscopic balance point compaction with cross suture-bridge technique for the treatment of avulsion fracture of the greater tuberosity of the humerus has advantages of decreased intraoperative blood loss, good reduction and healing, shoulder pain relief, early restoration of shoulder function and mobility, and few complications.
10.Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3β/STAT3 signaling axis.
Xiaolan LI ; Songhua HE ; Wei LIANG ; Weiquan ZHANG ; Xin CHEN ; Qiaofeng LI ; Xin YANG ; Yanying LIU ; Dan ZHU ; Li LI ; Buming LIU ; Zhiheng SU ; Jie CHEN ; Hongwei GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(2):113-126
Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKTSer473 and p-GSK3βSer9, and decreased the expression of p-STAT3Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice
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Animals
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Male
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Humans
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Mice, Inbred NOD
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Mice, SCID
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Marsdenia
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3 beta
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Molecular Docking Simulation
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Phosphatidylinositol 3-Kinases
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Tandem Mass Spectrometry
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Prostatic Neoplasms
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Apoptosis
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STAT3 Transcription Factor

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