Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

Objective To observe the effects of growth differentiation factor-15(GDF-15)on collateral circulation and cardiac function in rats with acute myocardial infarction(AMI)in relation to the nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods An AMI rat model was constructed by ligating the left anterior descending coronary artery.After modeling,the rats were divided randomly into Sham,Model,and GDF-15 groups(n=12 rats per group).Rats in the GDF-15 group were injected intraperitoneally with recombinant GDF-15 protein,and the other two groups were injected with the same amount of normal saline twice a week for 8 consecutive weeks.Cardiac function was detected by echocardiography.Pathological damage to rat myocardial tissue was detected by hematoxylin and eosin staining and the collateral circulation was observed by CD31 immunohistochemical staining.Vascular endothelial growth factor(VEGF)mRNA expression was detected by quantitative polymerase chain reaction.Transcriptomic sequencing of heart tissues in the model and GDF-15 groups was performed and differentially expressed genes(DEGs)were screened.Pathway enrichment analysis of the DEGS was carried out according to the Kyoto Encyclopedia of Genes and Genomes(KEGG).Nitric oxide(NO),reactive oxygen species(ROS),and cGMP were detected using kits,and VEGF,endothelial nitric oxide synthase(eNOS)monomer,p-eNOSser1177monomer,eNOS dimer,and PKG protein were detected by Western blot.Results Left ventricular end-systolic diameter(LVEDs)and left ventricular end-diastolic diameter(LVEDd)were increased(P＜0.001),and left ventricular ejection fraction(LVEF)and the short-axis shortening rate(FS)were decreased in the Model group compared with the Sham group(P＜0.001).Myocardial cell necrosis was more severe,vascular density in the infarcted area was decreased(P＜0.05),but VEGF mRNA and protein levels were no change(P＞0.05),and levels of NO,eNOS dimer,cGMP,and PKG protein were decreased(P＜0.05),and expression levels of ROS,eNOS monomer,and p-eNOSser1177 monomer were increased(P＜0.05).LVEDs and LVEDd decreased(P＜0.05),LVEF and FS increased(P＜0.01),myocardial cell necrosis was relieved,vascular density in the infarcted area increased significantly(P＜0.0001),and VEGF mRNA levels increased(P＜0.0001),compared with the Model group.Transcriptomic sequencing identified 324 DEGs,including 230 up-regulated and 94 down-regulated genes.According to KEGG enrichment analysis,the cGMP-PKG signaling pathway showed the most significant difference in the T20 pathway.VEGF,NO,eNOS dimer,cGMP,and PKG protein levels were all increased(P＜0.05),while ROS,eNOS monomer,and p-eNOSser1177 monomer were decreased in the GDF-15 group(P＜0.05).Conclusions GDF-15 can promote collateral circulation in ischemic myocardium and improve cardiac function by inhibiting eNOS decoupling and activating the NO/cGMP/PKG pathway.

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.

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.

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.

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.

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.

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.

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.

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.