1.Inhibitory effect of gossypol on migration of gastric carcinoma cell lines through Akt/β-catenin passway
Dan YANG ; Li WANG ; Zhu LI ; Zhaoyang LIU ; Chang LIU ; Li GUO ; Jia FU ; Rong QI ; Junping WANG
Chinese Pharmacological Bulletin 2015;(6):860-864
Aim To investigate the inhibitory effects of gossypol on migration in gastric carcinoma cell lines and its mechanisms. Methods Gastric carcinoma cells were treated with gossypol at different concentra-tions. The effects of gossypol on cells proliferation were measured using the MTT assay. The migration of gas-tric carcinoma cells was detected by transwell assay. The activation of Akt/β-catenin pathway and the ex-pressions of pathway related proteins ( p-Akt,β-cate-nin, cyclin D1, MMP-2, E-cadherin and vimentin ) were detected by Western blot. Results Gossypol treatment could significantly inhibit the proliferation of gastric carcinoma cells in a dose-dependent manner. Transwell assay showed that the migration ability of
gastric carcinoma cells was significantly decreased. The inhibitory effect of gossypol on cells migration was more significant than the effect of gossypol on cells prolifera-tion. Compared with the control group, treatment with gossypol significantly suppressed the expressions of p-Akt,β-catenin, cyclin D1, MMP-2 and vimentin pro-tein, whereas the expression of E-cadherin was signifi-cantly up-regulated in gastric carcinoma cells in a dose-dependent manner. Conclusion These results demonstrate that gossypol represses cell migration of gastric carcinoma cells through the down-regulation of the activity of Akt/β-catenin pathway.
2.Efficacy and safety of PD-1 inhibitors combined with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer
Congwei WANG ; Qizhe WU ; Yuankang FENG ; Bo FU ; Zhaoyang LIU ; Zhengguo ZHANG ; Jinjian YANG ; Zhankui JIA
Chinese Journal of Urology 2023;44(11):806-811
Objective:To compare the efficacy and safety of programmed death-1(PD-1)inhibitors in combination with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer.Methods:A retrospective analysis was performed on the clinical data of 77 cases of metastatic bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2022. According to the different clinical treatment regimens, they were divided into two groups. Patients treated with PD-1 inhibitors combined with gemcitabine and cisplatin (GC) regimen were referred to as IGC group, and patients who received GC chemotherapy alone were referred to as GC group. There were 24 cases in IGC group, including 18 males and 6 females, with a median age of 60 (56, 67) years old. Seventeen cases had a history of smoking. Fifteen cases had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 9 cases had a score of 1. Twenty-three cases suffered distant metastasis (stage M 1). Two cases suffered lymph node metastasis only, 6 cases with liver metastasis, 8 cases with lung metastasis, and 8 cases with bone metastasis. There were 53 cases in GC group, including 45 males and 8 females, with a median age of 63 (55, 69) years old. Thirty-one cases had a history of smoking. Thirty cases had an ECOG score of 0 and 23 cases had a score of 1, 48 cases suffered stage M 1, 2 cases suffered lymph node metastasis only. Nineteen cases suffered liver metastasis. Twenty-seven cases suffered lung metastasis. And 23 cases suffered bone metastasis. There was no statistically significant difference in the above general information between the two groups ( P>0.05). Kaplan-Meier method was used to plot the survival curves, and the difference of median progression-free survival (mPFS) and median overall survival (mOS) between the two groups was compared by log-rank test. Finally, the difference in adverse reactions between the two groups was compared. Results:The objective response rate (ORR) was 41.7% and the disease control rate (DCR) was 87.5% in the IGC group.As a comparison, the ORR was 43.4% and the DCR was 83.0% in the GC group. The differences in ORR ( P=0.887) and DCR ( P=0.871) between the two groups were not statistically significant. All patients were followed up for 3 to 45 months, with a median follow-up time of 24 (14, 43) months. The mPFS was 7.0 (95% CI 5.7-8.3) months in the GC group and 8.0 (95% CI 3.0-13.1) months in the IGC group, and the difference was statistically significant between the two groups ( P=0.026). The mOS of patients in the GC group was 16.0 (95% CI 14.4-17.6) months, the mOS was not yet reached in the IGC group, and patients in the IGC group had longer mOS with a statistically significant difference ( P=0.022). All patients experienced treatment-related adverse reactions. Grade 3-4 adverse reactions occurred in 8 cases (33.3%) in the IGC group and in 16 cases (30.2%) in the GC group, and no adverse reaction-related deaths were observed( P=0.992). The most common adverse reactions in both groups were anemia, including 18 cases (75.0%) in IGC group and 38 cases (71.7%) in GC group. There were 4 cases (16.7%) of grade 1-2 hypothyroidism in the IGC group but no patients with hypothyroidism were found in the GC group, and the difference was statistically significant ( P=0.012). There were 8 cases (33.3%) and 4 cases (7.5%) of grade 1-2 skin adverse reactions in the IGC and GC groups, respectively, and the difference was statistically significant ( P=0.011). The immune-related adverse reactions of PD-1 inhibitors in IGC group were 1 case of hyperthyroidism (4.2%), 4 cases of hypothyroidism (16.7%), 1 case of adrenal insufficiency (4.2%), and 1 case of immune colitis (4.2%). Conclusions:Compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy for metastatic bladder cancer can effectively prolong the mPFS and median mOS. The adverse reactions of the two groups were tolerable, and there was no significant difference in the incidence of grade 3-4 adverse reactions. In general, PD-1 inhibitors combined with chemotherapy in the treatment of metastatic bladder cancer is safe and feasible, but attention should be paid to the immune-related adverse reactions of PD-1 inhibitors.
3.Application value of psTg combined with lymph node ratio in prognosis of papillary thyroid cancer patients treated with 131I
Zhaoyang JIA ; Deyu LI ; Sen WANG ; Guang YANG ; Kai CHEN ; Lijun WANG ; Wei FAN ; Hui YANG ; Wenliang LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(7):407-411
Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.
4.Remnant cholesterol is associated with triglyceride and glucose index in young and middle-aged patients with ischemic stroke
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):910-914
【Objective】 To investigate the association between remnant cholesterol (RC) and triglyceride and glucose (TyG) index in young and middle-aged patients with ischemic stroke. 【Methods】 A total of 268 patients were divided into two groups, namely low TyG index group (n=134) and high TyG index group (n=134). Characteristics of the study population and metabolism risk factors (TC, TG, HDL-C, LDL-C, UA) were collected from biochemical test results. Spearman correlation analysis was used to analyze the correlation between metabolism risk factors and TyG index. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for RC and TyG index. 【Results】 Compared with the low TyG index group, significant differences were observed for BMI, history of diabetes, history of hypertension, SBP, DBP, FBG, TC, TG, LDL-C, RC, UA, and TyG index in high TyG index group. No significant differences were observed in age, gender, smoking status, or drinking status, HDL-C between the two groups. Spearman correlation analysis indicated that significant linear associations were observed between BMI, SBP, DBP, FBG, TC, TG, HDL-C, LDL-C, RC, UA and TyG index. Logistic regression analysis revealed that the RC, BMI, hypertension, diabetes, TC, LDL-C, and UA were significantly associated with the risk of increased level of TyG index. After adjusted analysis by RC, BMI, hypertension, diabetes, TC, LDL-C, and UA, only RC was significantly associated with an increased risk of increased level of TyG index. 【Conclusion】 Remnant cholesterol was associated with an increased risk of elevated TyG index level in young and middle-aged patients with ischemic stroke.
5.Association between impaired sensitivity to thyroid hormones and ischemic stroke in euthyroid population with hypertension and sex difference in this association
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):763-768
【Objective】 To investigate the associations between thyroid hormone sensitivity indices in euthyroid patients with hypertension and the risk of ischemic stroke, as well as gender difference in this association. 【Methods】 We selected 760 hypertensive patients admitted to the Geriatric Neurology Department and outpatient clinic in The Second Affiliated Hospital of Xi’an Jiaotong University between April 2021 and May 2022. We collected their basic characteristics, blood biochemical parameters, thyroid indices, and brain magnetic resonance imaging information. All the patients were divided into two groups based on the clinical manifestations and brain magnetic resonance imaging: hypertension combined with ischemic stroke (n=526) and control (n=234) groups. Independent sample t-tests or non-parametric tests were used to compare the differences in thyroid hormone sensitivity indicators between the two groups. Spearman correlation analysis was used to analyze the correlation between serum thyroid indices and ischemic stroke. Multivariate conditional Logistic regression analysis was made to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid indices and ischemic stroke. 【Results】 There were statistically significant differences between the two groups in terms of age, gender, TC, LDL-c, HDL-c, systolic blood pressure, FT3/FT4, TFQI, and PTFQI (all P<0.05). However, there was no statistically significant difference between the two groups in weight, smoking, drinking, history of diabetes, TG, FBG, diastolic blood pressure, TSHI, or TT4RI (all P>0.05). The results of Spearman correlation analysis showed a negative correlation between FT3/FT4 and ischemic stroke (P<0.05), but a positive correlation of TFQI and PTFQI with ischemic stroke (P<0.05) in euthyroid patients with hypertension. Logistic regression analysis showed that FT3/FT4 was significantly associated with ischemic stroke in euthyroid patients with hypertension (P=0.001), with OR (95% CI) of 0.001 (0.000, 0.058). After stratifying by gender, Logistic regression analysis found that FT3/FT4, TFQI, and PTFQI were associated with an increased risk of ischemic stroke in female patients, with OR (95% CI) of 0.000 (0.000, 0.001), 3.132 (1.415, 6.930), and 3.010 (1.406, 6.445), respectively. 【Conclusion】 Lower serum FT3/FT4 ratio is associated with an increased risk of ischemic stroke in euthyroid patients with hypertension, and the significant association of TFQI and PTFQI with the risk of ischemic stroke is found in females.
6.Impaired sensitivity to thyroid hormones is associated with ischemic stroke in young and middle-aged euthyroid population
Youyou ZHANG ; Ruirui JIA ; Dong CHEN ; Fuhua GONG ; Long WANG ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):938-943
【Objective】 To investigate the association of thyroid indices with the prevalence of ischemic stroke in young and middle-aged euthyroid population. 【Methods】 For this retrospective study, 620 euthyroid patients aged from 18 to 65 years were divided into ischemic stroke group (n=308) and non-ischemic stroke group (n=312). The characteristics of the study population; serum thyroid indices, i.e., free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), were collected from biochemical test results. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid indices and ischemic stroke. 【Results】 Compared with non-ischemic stroke group, significant differences were observed in age, gender, weight, smoking status, drinking status, history of hypertension and diabetes, SBP, DBP, FBG, TC, HDL-C, LDL-C, FT3, FT4, FT3/FT4, TFQI, and PTFQI in ischemic stroke patients (all P<0.05). No significant differences were observed for TG, TSH, TSHI, or TT4RI between the two groups (all P>0.05). Logistic regression analysis revealed that lower FT3 [OR (95% CI) =0.722 (0.547~0.955) , P=0.022] and FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.001] , FT4 [OR (95% CI) =1.099 (1.011~1.194) , P=0.026] were significantly associated with an increased risk of ischemic stroke. After stratified analysis by hypertension, FT4 [OR (95% CI) =1.133 (1.021~1.257) , P=0.019] , lower FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.003] , TFQI [ OR (95% CI) =1.854 (1.026~3.350) , P=0.041] , and PTFQI [OR (95% CI) =1.871 (1.065~3.288) , P=0.029] were significantly associated with an increased risk of ischemic stroke in patients combined with hypertension, while after stratified analysis by diabetes, we only found that lower FT3/FT4 ratio [OR (95% CI) =0.730 (0.559~0.953) , 0.704 (0.536~0.944) , P=0.021] and FT4 [OR (95% CI) =1.170 (1.025~1.335) , P=0.026] were significantly associated with an increased risk of ischemic stroke in patients combined with diabetes. 【Conclusion】 FT3, FT4, and FT3/FT4 ratio are associated with an increased risk for ischemic stroke in young and middle-aged euthyroid population; TFQI and PTFQ are associated with an increased risk for ischemic stroke in patients combined with hypertension.
7.Diagnosis and treatment recommendations of dialysis patients with SARS-CoV-2 infection for primary care clinicians
Rongguo FU ; Zhao CHEN ; Lining JIA ; Li WANG ; Jin HAN ; Lifang TIAN ; Xianghui CHEN ; Linting WEI ; Fuqian LEI ; Jiamei LU ; Xiaoqin MA ; Li ZHAO ; Shizhuo WEI ; Jing LIU ; Zhaoyang DUAN ; Jie GAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):353-360
End-stage renal disease (ESRD) patients undergoing outpatient hemodialysis (HD) and home peritoneal dialysis (PD) are high risk population of severe and critical types caused by SARS-CoV-2 infection. In order to improve the quality of diagnosis and treatment in dialysis patients with SARS-CoV-2 infection, we wrote this recommendation for primary care clinicians. During the epidemic period of SARS-CoV-2 infection, all patients should be instructed to strengthen self-management. Once the SARS-CoV-2 infection was found in dialysis patients, early stratified management should be carried out within 72 hours after the first positive nucleic acid or antigen test results, which includes early antiviral therapy, early recognition, and transferring severe patients from community or primary hospital to a referral hospital promptly. Guidance for dietary and sports rehabilitation after SARS-CoV-2 infection should also be started as soon as possible.