1.Combined with systematic pharmacology and metabonomics to explore the mechanism of Baicalein in the treatment of hyperuricemia
Jingzhen LIANG ; Yingjie GAO ; Wenqian YE ; Bingyan WEI ; Zhaoyang CHEN ; Fan YANG
Chinese Journal of Comparative Medicine 2024;34(9):1-11
		                        		
		                        			
		                        			Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.
		                        		
		                        		
		                        		
		                        	
2.Efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with advanced hepatocellular carcinoma
Long CHENG ; Yue ZHANG ; Yushen LIU ; Zhaoqing DU ; Zhaoyang GUO ; Yangwei FAN ; Ting LI ; Xu GAO ; Enrui XIE ; Zixuan XING ; Wenhua WU ; Yinying WU ; Mingbo YANG ; Jie LI ; Yu ZHANG ; Wen KANG ; Wenjun WANG ; Fanpu JI ; Jiang GUO ; Ning GAO
Journal of Clinical Hepatology 2024;40(10):2034-2041
		                        		
		                        			
		                        			Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(<65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P>0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P>0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged<65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.
		                        		
		                        		
		                        		
		                        	
3.Establishment and evaluation of a predicative model in diagnosing unilateral primary aldosteronism
Yangjie ZENG ; Fan YANG ; Yijie WANG ; Zhaoyang TIAN ; Menglian LI ; Ping LI ; Dalong ZHU
Chinese Journal of Endocrinology and Metabolism 2023;39(10):870-875
		                        		
		                        			
		                        			Primary aldosteronism(PA) is a common cause of secondary hypertension, with adrenal vein sampling(AVS)being the gold standard for etiological typing diagnosis. This retrospective study analyzed data from patients diagnosed with PA who underwent AVS or unilateral adrenalectomy at Nanjing Drum Tower Hospital′s Endocrinology Department from July 2018 to August 2021. Using multivariate logistic regression analysis, factors associated with unilateral aldosterone hypersecretion were identified. Based on these factors, a predictive model for diagnosing unilateral primary aldosteronism(UPA)was established: age <40 years, plasma aldosterone concentration(PAC)>15 ng/dL, adrenal CT indicating an unilateral typical adenoma, and spontaneous hypokalemia. This predictive model could help 14% of PA patients avoid unnecessary AVS procedures.
		                        		
		                        		
		                        		
		                        	
4.The diagnostic significance of tumor diameter and unenhanced CT attenuation value in distinguishing benign from malignant adrenal masses
Menglian LI ; Ziwei ZHANG ; Mengsi LIU ; Yangjie ZENG ; Zhaoyang TIAN ; Fan YANG ; Ping LI
Chinese Journal of Endocrinology and Metabolism 2023;39(12):1016-1022
		                        		
		                        			
		                        			Objective:To explore the pathological characteristics of adrenal masses based on various tumor diameter and unenhanced computed tomography(CT) attenuation value, and evaluate the value of the two parameters in the assessment of the benign and malignant nature of adrenal masses.Methods:The data of 1 367 patients who underwent adrenalectomy in Nanjing Drum Tower Hospital from January 2017 to October 2022 were retrospectively collected. The adrenal masses were divided into four groups according to tumor diameter and unenhanced CT attenuation value, and the clinical and histopathological characteristics of the four groups were compared respectively. Logistic regression was used to analyze the correlation between tumor diameter, non-contrast CT attenuation value and malignant adrenal masses, and receiver operating characteristic(ROC) curve was used to assess the diagnostic value of both in benign and malignant adrenal masses.Results:The proportion of adrenocortical carcinoma and other malignant tumors increased with the rise of tumor diameter or unenhanced CT attenuation value. After adjusting for age and gender, tumor diameter( OR=1.624, 95% CI 1.464-1.803, P<0.001) and unenhanced CT attenuation value( OR=1.108, 95% CI 1.079-1.138, P<0.001) were predictors of malignant adrenal masses. The tumor diameter and unenhanced CT attenuation value in diagnosing malignant adrenal masses had area under the ROC curve(AUC) of 0.838 and 0.892, respectively. With the optimal cut-off values of >3.4 cm and >30 HU, the sensitivity was 75.5% and 83.7%, and the specificity was 80.5% and 84.4%, respectively. The combination of tumor diameter >3.4 cm and unenhanced CT attenuation value >20 HU had an AUC of 0.927, with a sensitivity of 71.4% and a specificity of 90.1% in diagnosing malignant adrenal masses. Conclusions:Tumor diameter and unenhanced CT attenuation value has important significance in the differential diagnosis of benign and malignant adrenal masses. A combination of tumor diameter (>3.4 cm) and unenhanced CT attenuation value (>20 HU) demonstrates best diagnostic efficiency. Clinical application of this combined index can effectively diagnose malignant adrenal masses while avoiding unnecessary investigations or surgery.
		                        		
		                        		
		                        		
		                        	
5.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.
		                        		
		                        		
		                        		
		                        	
6.Serum endothelin-1 level in children with osteosarcoma and its correlation with lung metastasis
Zhaoyang FAN ; Caixing YIN ; Shiwan YU ; Lihua YAN ; Wenfeng XIAN ; Yongxi LIU
Chinese Journal of Applied Clinical Pediatrics 2021;36(15):1172-1175
		                        		
		                        			
		                        			Objective:To investigate the serum levels, diagnosis and prognosis value of endothelin-1(ET-1) in children suffering from lung metastasis of osteosarcoma.Methods:A total of 84 children with osteosarcoma, 67 children with lung metastasis of osteosarcoma and 35 healthy people from January 1, 2013 to January 1, 2018 in Second People′s Hospital of Nanyang were retrospectively included.The serum level of ET-1 was measured by performing enzyme linked immunosorbent assay(ELISA) methods and the influencing factors of serum ET-1 levels in children with lung metastasis of osteosarcoma were conducted by Logistic regression analysis.The clinical value of ET-1 in the prediction of the incidence of lung metastasis in children with osteosarcoma was analyzed by receiver operating characteristic (ROC) curve.Forty-five children with lung metastasis of osteosarcoma were followed up for 18 months and the prognosis value of serum ET-1 levels in children with lung metastasis of osteosarcoma was evaluated by Kaplan-Meier survival analysis. Results:The serum ET-1 level in children with lung metastasis of osteosarcoma was 97.23 (65.13, 134.98) ng/L and significantly higher than osteosarcoma group 60.21 (43.12, 74.63) ng/L and healthy control group 34.45 (12.01, 63.03) ng/L, respectively ( Z=-5.671, -4.92, all P<0.05), with significant differences. Logistic regression analysis proved that lung bilateral involvement ( OR=3.449), numbers of lung metastases (more than 3)( OR=3.449), average diameter of lung metastases (more than 5 cm) ( OR=6.501) and extrapulmonary metastasis ( OR=4.369) were independent risk factors for elevated serum ET-1 levels in children developing lung metastasis of osteosarcoma.The predictive value of ET-1 in the incidence of lung metastasis in children with osteosarcoma was significant (area under ROC curve: 0.841). When the cut-off value was 94.27 ng/L, the sensitivity and specificity were 88.5% and 92.6%, respectively.Survival analysis revealed that higher levels of ET-1 was correlated with poor prognosis ( OR=3.287, 95% CI: 1.119-9.547). Conclusions:The serum levels of ET-1 in children with lung metastasis of osteosarcoma are significantly elevated.ET-1 is a serological marker for the differential diagnosis of lung metastasis of osteosarcoma.Moreover, the higher levels of ET-1 are correlated with poor prognosis in children with lung metastasis of osteosarcoma.
		                        		
		                        		
		                        		
		                        	
7.Effect of occupational factors on pre-diabetes mellitus among iron and steel workers
Yajing LIAO ; Chuxuan XU ; Chongqi MA ; Zhenwei QIN ; Yajiao SU ; Hongru ZHU ; Xiaotong ZHANG ; Chan LI ; Xiaoming LI ; Zhaoyang WANG ; Juxiang YUAN ; Hongmin FAN
Chinese Journal of Epidemiology 2020;41(6):929-933
		                        		
		                        			
		                        			Objective:To investigate the prevalence of pre-diabetes mellitus (PDM) and the impact of occupation-related factors on PDM, among workers from a steel company in Tangshan city, Hebei province.Methods:Clustering sampling method was used to select a steel company and to carry out occupational health-related physical checkup programs for eligible workers who had working in this company for longer than one year. The study began in February and ended up in June, 2017. Workers who were with FPG level as ≤6.9 mmol/L, and free from diabetes, were selected as the subjects for this study. Questionnaires were used and physical examinations and FPG testing conducted.Results:The total number of subjects in this study was 4 173, of which 2 648 appeared as pre-diabetic, with the prevalence rate as 63.4 %. Increase of the PDM prevalence was in parallel with the length of service, among the workers. The risk for the pre-diabetes in those who worked more than 8 hours per day was 1.696 times higher than those who worked less than or equal to 8 h/d (95 %CI:1.517-1.937). Compared with those workers without exposures to heat, noise or carbon monoxides, the proportion of pre-diabetes appeared higher in workers exposed to heat, noise or CO with OR=1.782 (95 %CI: 1.205-2.636), 1.815 (95 %CI: 1.209-2.794) and 1.653 (95 %CI: 1.158-2.361), respectively. Risks for those who were exposed to heat or noise were higher than those who were free from exposure to any occupational hazards ( OR=2.098, 95 %CI: 1.296-3.397). Prevalence rates of pre-diabetes in those who were exposed to heat, noise or CO, were higher than that those who were not. Conclusion:Working hours and exposures to heat, noise or CO appeared as influential factors on PDM.
		                        		
		                        		
		                        		
		                        	
8.A case-control study on effect of occupational factor exposures on carotid atherosclerosis in steel workers
Zhenwei QIN ; Yajiao SU ; Haitao WANG ; Hongru ZHU ; Xiaotong ZHANG ; Chan LI ; Xiaoming LI ; Zhaoyang WANG ; Juxiang YUAN ; Hongmin FAN
Chinese Journal of Epidemiology 2020;41(11):1836-1842
		                        		
		                        			
		                        			Objective:To investigate the effect of occupational factor exposures on carotid atherosclerosis (CAS) in steel workers.Methods:A frequency matched case-control study was conducted by age and factory proportion. A total of 1 033 workers with carotid atherosclerosis diagnosed by ultrasonography examination from February to June 2017 were selected as case group, and 1 033 workers without carotid atherosclerosis indicated by physical examination at the same time were selected as control group. The basic information of the workers, such as diet pattern, lifestyle, serum biochemical index and occupation history, were collected. The effects of occupational hazards on carotid atherosclerosis were analyzed by univariate and multivariate logistic regression analyses. The combined effects of various occupational hazards on carotid atherosclerosis were evaluated by environmental risk score (ERS).Results:High temperature, noise, occupational stress and night shift days increased the risk of CAS. With the increase of cumulative high temperature and noise exposure, occupational stress and night shift days, the risk of CAS increased (trend text: χ2=37.53, P<0.01; χ2=16.98, P<0.01; χ2=13.93, P<0.01; χ2=5.59, P<0.05). After adjustment of covariates, compared with P 20 group, the risk of carotid artery in P 40, P 60, P 80 and P 100 groups were as follows: high temperature 1.61 (1.19-2.18), 1.69 (1.25-2.30), 1.84 (1.36-2.49), 2.43 (1.77-3.34); noise 1.70 (1.15-2.52), 1.68 (1.20-2.35), 1.80 (1.34-2.42), 2.23 (1.53-3.26); occupational stress 1.39 (1.04- 1.86), 1.41 (1.06-1.89), 1.45(1.09-1.95), 1.48 (1.10-1.98); night shift days 1.58 (1.08-2.33), 1.66 (1.12-2.47), 1.55 (1.04-2.31), 1.76 (1.17-2.64). The results of the environmental risk score showed that the risk of carotid atherosclerosis increased with the increase of ERS (ERS trend text χ2=51.61, P<0.01); RCS results showed that there was a linear relationship between ERS and CAS in steel workers( P<0.01). Linear dose-response relationship existed between ERS and CAS (nonlinear test P>0.05). Conclusions:High temperature, noise, occupational stress and night shift days were related to carotid atherosclerosis. Linear dose-response relationship existed between ERS and CAS in steel workers.
		                        		
		                        		
		                        		
		                        	
9.Study on the influence of sleeve height and implant length on accuracy of static computer-assisted implant surgery
Qingfu WANG ; Zhengdi HE ; Haiyang YU ; Xiaohai QIU ; Yanying WANG ; Jing HAN ; Jing YANG ; Xiaodi SUN ; Xiaoban LI ; Zhaoyang LI ; Hui FAN ; Jian ZHANG
Chinese Journal of Stomatology 2020;55(11):902-907
		                        		
		                        			
		                        			Objective:To evaluate the influence of the sleeve lengths and implant lengths on accuracy of static computer-assisted implant surgery (sCAIS).Methods:Twenty-eight models of bilateral mandibular single tooth loss were included. Fifty-five implants were placed under the guidance of sCAIS (Straumann Bone Level 4.1 mm×10 mm). According to the height of metal sleeve of static guide plate, 55 implants were divided into 11 groups (free hand group, 1 mm group, 2 mm group, 3 mm group, 4 mm group, 5 mm group, 6 mm group, 7 mm group, 8 mm group, 9 mm group, 10 mm group), with 5 implants in each group. Eight research models were included. Group with 5 mm sleeve guides were used to place implants of different length, (Straumann Bone Level width 4.1 mm, height was 8 mm, 10 mm and 14 mm), 5 implants in each group. Eighteen patients with mandibular single tooth loss were included in the Department of Oral Implantology, Tianjin Stomatological Hospital from October 2018 to June 2019. There were 10 males and 8 females, 18-46(33.7±7.9) years old. A total of 18 implants were implanted and divided into 3 groups (free hand group, 3 mm group and 5 mm group) with 6 implants in each group. Digital software was used to compare the implant positions before and after implantation. Non-parametric Kruskal-Wallis test or one-way ANOVA were used to analyze the results.Results:There was no significant difference in implant vertical deviation between different sleeve height groups (1-10 mm) and free hand group, but the neck deviation in free hand group[(1.04±0.13) mm] was significantly higher than that in different sleeve height groups (1-10 mm) ( P<0.05). The tip deviations of free hand group, 1 mm group and 2 mm group [(1.32±0.43), (0.83±0.10) and (0.78±0.11) mm, respectively] was significantly higher than that of 10 mm group [(0.31±0.14) mm]( P<0.05). The angle deviation of free hand group and 1 mm group (3.99°±0.85° and 2.59°±0.69°), respectively] was significantly higher than that of 10 mm group (0.61°±0.03°) ( P<0.05). The tip deviations of implants in the 14 mm group [(0.83±0.22) mm] was significantly higher than that in the 8 mm and 10 mm groups [(0.44±0.07) and (0.49±0.06) mm, respectively]. Clinical studies showed that there was no significant difference in neck deviation, tip deviation and angle deviation between 3 mm group and 5 mm group ( P>0.05), but deviations were significantly lower than those in free hand group ( P<0.05). Conclusions:The length of the sleeves has significant influence on the accuracy of the surgical guide. There was no significant difference in accuracy of the implant guide with 3 mm or 5 mm metal sleeves. The vitro study has some limitations and needs further systematic research.
		                        		
		                        		
		                        		
		                        	
10.Gigantol inhibits the proliferation, migration and invasion of osteosarcoma cells by NF-κB/PRL-3 pathway
FAN Zhaoyang ; XIAN Wenfeng ; LIU Yongxi ; ZHANG Chao
Chinese Journal of Cancer Biotherapy 2019;26(10):1095-1100
		                        		
		                        			
		                        			To study the inhibitory effect of gigantol on proliferation, migration and invasion of human osteosarcoma U20S cells and to explore the mechanism. Methods: After being treated with different concentrations (10, 25, 50, 75, 100, 150 µmol/L) of gigantol for 24 and 48 h, the proliferation of U20S cells was detected by CCK-8 assay. Transwell assay was used to detect the effects of 25 µmol/L and 50 µmol/L gigantol on the migration and invasion abilities of U20S cells. The lipopolysaccharide (LPS) was used to induce inflammatory reaction in U20S cells before gigantol treatment; qPCR and WB were used to detect the mRNA and protein expressions of NF-κB (p65), TNF-α, IL-6 and PRL-3, respectively. Results: Different concentrations of gigantol could all inhibit the proliferation of sarcoma U20S cells at different time (P<0.05 or P<0.01). The 25 µmol/L and 50 µmol/L of gigantol could significantly inhibit the migration and invasion of osteosarcoma U20S cells (all P<0.01); at the same time, it could inhibit the protein expressions of NF-κB, TNF-α, IL-6 and PRL-3 (P<0.05 or P<0.01). After LPS induction, the mRNA and protein expressions of NF-κB, TNF-α, IL-6 and PRL-3 in U20S cells were significantly increased (all P<0.01); however, the consequent treatment with gigantol (25 and 50 µmol/L) reversed the effects of LPS on U20S cells obviously (P<0.05 or P<0.01). Conclusion: Gigantol can inhibit the proliferation, migration and invasion of osteosarcoma U20S cells, and its mechanism may be related to the regulation of NF-κB/PRL-3 signaling pathway. 
		                        		
		                        		
		                        		
		                        	
            
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