The purpose of this study was to investigate the pharmacokinetic interaction between sunitinib and ramipril in rats. Eighteen male SD rats were divided into three groups, with each group being assigned to orally receive sunitinib, ramipril, sunitinib and ramipril, respectively, for ten days. Blood samples were collected at dif-ferent times after first-day and tenth-day administration. The concentrations of ramiprilat and sunitinib in rat plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated and statistically analyzed. Compared with the administration of ramipril alone, after a single-dose combined administration, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ remained unchanged. These results indicated that the ab-sorption rate of ramiprilat increased and the elimination rate decreased, but total absorption degree was not changed. After multiple-dose administrations, CL of ramiprilat decreased and AUC0-∞ increased obviously. It sug-gested that accumulation of ramiprilat occurred in body and the drug elimination became slower. No obvious difference of sunitinib pharmacokinetic behavior was found when it was given in combination with ramipril after a single-dose administration or multiple-dose administration. Sunitinib decreased the elimination of ramiprilat after co-administration in company with drug accumulation in body after multiple-dose co-administration. The study showed that there were pharmacokinetic interactions between sunitinib and ramipril in SD rats.

OBJECTIVE: To evaluate the curative effect of continuous positive airway pressure(CPAP) combined with modified oral appliance (MOA) in the treatment of severe OSAHS. METHOD: The research chose 120 male patients with severe OSAHS. They were treated with CPAP and MOA (30 cases), CPAP (30 cases), and MOA (30 cases) respectively. At the same time, the rest 30 cases without any treatment were in control group (matching factors: age, gender, IBM). After 3 months treatment, the characteristics of PSG and respiratory machine wear condition were observated in four groups. RESULT The ESS score in CPAP and MOA group was significantly lower than that in other groups (P < 0.05); After 3 months treatment, the AHI, awake index (AI), and Ni (non-rapid eyemovement sleep1, N1) and N2 (non-rapid eye movement sleep2, N2) period of total sleep time (TST) percentage in CPAP assisted MOA group and CPAP group were significantly lower than that in MOA group and control group (P < 0.05); Sleep efficiency, ESS score, average blood oxygen saturation (MSaO₂), the lowest oxygen saturation (LSaO₂), slow wave sleep phases (SWS) and rapid eyemovement sleep (REM) accounted for the proportion of TST increased significantly (P < 0.05); There was no significant difference between CPAP assisted MOA group and CPAP group in AHI, MSaO₂, AI, sleep efficiency, N1, N2, SWS and REM percentage of TST and ESS score. The LSaO₂ and average machine time in CPAP assisted MOA group were significantly greater than that in CPAP group (P < 0.05), but 90% pressure and average air leakage were significantly lower in the CPAP group (P < 0.05) CONCLUSION: The curative effect of CPCR combined with modified oral appliance was better than CPCR or MOA alone in the treatment of severe OSAHS.
Continuous Positive Airway Pressure ; Humans ; Male ; Oximetry ; Sleep ; Sleep Apnea, Obstructive ; therapy

ObjectiveTo investigate the methylation status in the promoter region of secreting frizzled related protein 2 (SFRP2) gene in patients with myelodyplastic sydrome (MDS) and to initially explore the relationship between the methylation of this gene and prognosis/survival time.MethodsMSP method was applied to examine the promoter methylation of SFRP2 gene in 43 bone marrow or peripheral blood samples of MDS patients.As controls,70 normal peripheral blood samples from volunteers of general outpatients were examined.Then some of the patients were followed up.ResultsIn 43 patients of MDS,10 samples (23.3 ％)showed SFRP2 gene methylation,and all of them were semi-methylation status.In 70 controls,no sample showed SFRP2 gene methylation.The frequency of SFRP2 gene methylation in MDS patients was significantly higher than that in controls (x2 =17.86,P ＜0.0001).Of the 10 SFRP2 gene methylation samples,5 were bone marrow samples and 5 were peripheral blood samples.In this group of patients,3 patients were diagnosed as RA,1 patient was diagnosed as RAS,2 patients were diagnosed as RCMD,3 patients were diagnosed as RAEB and 1 patient was diagnosed as MDS-U.There was no significant difference between the different sample source (bone marrow or peripheral blood) for the results of the methylation status (x2 =0.912,P ＞0.05).Either no significant difference between the different sex,age,type,chromosome and WPSS score (all P ＞0.05).The progress of disease didn' t influence the methylation rate (P ＞0.05).16 patients accepted follow-up and 11patients died,3 patients went to AML.2 died patients showed SFRP2 gene methylation.The survival analyses showed no relationship between the methylation of this gene and survival time(x2 =0.022, P ＞0.05).ConclusionIn this MDS group,there is a high level of methyl-modification in SFRP2 gene.The methylation of SFRP2 may be one of the molecular mechanisms that contribute to the progress of patients with MDS.The peripheral blood sample maybe a better substitute in detection of SFRP2 with MDS.

OBJECTIVE: To explore the changes of serum interleukin-6 (IL-6) level in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and OSAHS associated type 2 diabetes mellitus (T2DM) and their significance. METHOD: All observed subjects were divided into 3 groups: 20 cases of normal subjects, 35 cases of simple OSAHS patients, 48 cases of OSAHS associated T2DM patients, IL-6 concentrations of serum were measured by the enzyme-linked immunosorbent. RESULT: IL-6 level was higher in the group of OSAHS with T2DM than the group of OSAHS and the healthy control group (P < 0.05); IL-6 level was higher in the simple OSAHS group than the healthy controls. CONCLUSION IL-6 and other inflammatory factors may involved pathological physiological process in OSAHS patients sugar metabolic abnormalities; and is associated with the development of OSAHS associated with type 2 diabetes.
Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; complications ; Humans ; Interleukin-6 ; blood ; Sleep Apnea, Obstructive ; blood ; complications

OBJECTIVE: To observe the clinical effect of nasal surgical expansion as basical surgical treatment of patients with OSAHS. METHOD: A total of 320 patients with OSAHS were retrospectively analyzed. The patient was diagnosed by PSG. The electronic nasopharyngolarygnoscope exam airway CT, and MRI were applied to determining the nasal plane block. According to the concrete reasons, the nasal endoscopic nasal septum corrective surgery and open surgery were carried out, respectively. Nasal sinus neoplasm resection of off shoring, inferior turbinate fracture surgery or inferior turbinate back-end 1/3 line expansion and low temperature plasma ablation of nasal surgery, respectively. Pittsburgh sleep quality index (PSQI), snore outcome survey (SOS), epworth sleepiness score (ESS), the lowest arterial oxygen saturation (LSaO2) and AHI, time and ratio of slow wave sleep (SWS) stage and rapid eye movement (REM) stage were applied to comparing the curative effect between pre-operation and post-operation periods. RESULT: Snoring, sleep apnea, subjective mental symptoms of all patients with OSAHS were improved after operation; PSQI, SOS and ESS score were improved compared to pretreatment (P < 0.05); according to the 2009 OSAHS diagnosis and curative effect evaluation standard, 38 cases cured, 189 cases had obvious effect, 93 cases effective, and the total effective rate was 100%; there was statistical difference between the pre-operative period and 6 months post-operative in PSQI, SOS and ESS, LSaO2, AHI and proportion of REM (P < 0.05); sleep structure was improved, time and proportion of SWS were increased after the operation (P < 0.05). CONCLUSION Solving the problem of nasal airway obstruction is the first step in surgical treatment of patients with OSAHS.
Endoscopy ; Humans ; Nasal Obstruction ; Nasal Septum ; surgery ; Nasal Surgical Procedures ; Oximetry ; Paranasal Sinus Neoplasms ; surgery ; Paranasal Sinuses ; pathology ; Reconstructive Surgical Procedures ; Retrospective Studies ; Sleep Apnea, Obstructive ; surgery ; Sleep Stages ; Sleep, REM ; Snoring ; Turbinates ; surgery

OBJECTIVE: To investigate the significance of tumor necrosis factor-alpha (TNF-α) and plasma endothelium (ET) in pathophysiologic process of patients with obstructive sleep apnea hypopnea syndrome(OSAHS) with type 2 diabetes mellitus (T2DM). METHOD: All observed subjects were divided into 4 groups. A number of 80 patients with OSAHS, 65 cases of OSAHS with T2DM patients, 20 patients with T2DM, and 32 cases of healthy control group were observed in this study. The serum levels of TNF-α and ET were detected by double antibody sandwich ELISA, the content of TNF-α and ET were compared between OSAHS group and OSAHS + T2DM group. It were also compared before and after treatment of CPAP or surgery. RESULT: TNF-α level is higher in OSAHS+T2DM group than that in the OSAHS group, T2DM group and the control group (P < 0.05); TNF-α level in OSAHS group and the T2DM group are higher than that in the control group (P < 0.05), but there was no difference in TNF-α level between the OSAHS group and the T2DM group. There was also no difference in ET level of the four groups. There were significant differences of TNF-α before and after treatment of CPAP or surgery in OSAHS group and OSAHS+T2DM group (P < 0.05). But there was no significant differences of ET before and after treatment of CPAP or surgery in the OSAHS+T2DM group (P > 0.05). CONCLUSION TNF-α may be involved in the development of OSAHS and T2DM, while ET may have little effect on the occurrence and development of OSAHS and T2DM.
Antibodies ; Diabetes Mellitus, Type 2 ; blood ; complications ; Endothelins ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Sleep Apnea, Obstructive ; blood ; complications ; Tumor Necrosis Factor-alpha ; blood

Objective:To investigate the value of multi-parametric analysis based on dual-layer detector spectral CT (DLCT) in predicting the initial recurrence risk for papillary thyroid carcinoma (PTC).Methods:From November 2021 to October 2022, 102 PTC patients confirmed by pathology were retrospectively collected at the First Affiliated Hospital of Nanjing Medical University in this cross-sectional study. There were 25 males and 77 females, with an age of (42±13) years old. The initial recurrence risk assessment for PTC patients was categorized into a low-risk group (75 cases) and an intermediate-high-risk group (27 cases). Clinical data, including age, gender, body mass index, history of nodular goiter, history of Hashimoto thyroiditis, and preoperative thyroid function, were collected. Tumor morphological features, including size, location, shape, aspect ratio, the degree of thyroid capsule contact, calcification, and cystic change, were evaluated. Quantitative DLCT parameters, including iodine concentration (IC), standardized iodine concentration (NIC), effective atomic number (Z eff), standardized effective atomic number (NZ eff), electronic density (ED), CT values under different energy levels (40-200 keV, 30 keV intervals) and slope of energy spectrum curve (λ HU) both in the arterial and venous phase were measured. The differences in clinical, morphological features, and spectral CT quantitative parameters between the two groups were compared using independent sample ttest, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analyses were used to construct three models based on clinical and morphological features, quantitative DLCT parameters and their combination, respectively. The receiver operating characteristic curve was used to evaluate the predictive performance of these models for the initial recurrence risk of PTC patients, and the area under the curve (AUC) was compared using the DeLong test. Results:Significant differences were found in gender, lesion long diameter, lesion short diameter and calcification between the low-risk group and intermediate-high-risk groups ( P<0.05). The arterial phase IC, arterial phase Z eff, arterial phase λ HU, arterial phase CT 40 keV, venous phase NIC and venous phase NZ eff in intermediate-high-risk group were significantly lower than those in the low-risk group ( P<0.05). The logistic regression analysis revealed that the clinical model included gender ( OR=2.895, 95% CI 1.047-8.002, P=0.040) and lesion long diameter ( OR=1.142, 95% CI 1.042-1.251, P=0.004), with an AUC of 0.720, sensitivity of 63.0%, and specificity of 78.7% in predicting the initial recurrence risk of PTC patients. The DLCT quantitative parameter model included arterial phase IC ( OR=0.580, 95% CI 0.370-0.908, P=0.017), venous phase NIC ( OR=0.077, 95% CI 0.011-0.536, P=0.010), and venous phase NZ eff ( OR=0.002, 95% CI 0.001-0.103, P=0.009), with an AUC of 0.774, sensitivity of 71.9%, and specificity of 70.0%. The AUC of the combined model was 0.857, with a sensitivity of 74.1%, and specificity of 88.0%, outperforming the clinical model ( Z=2.92, P=0.004) and the DLCT quantitative parameter model ( Z=2.07, P=0.046). Conclusion:Multi-parametric analysis based on DLCT can help predict the initial recurrence risk for PTC, and combining it with clinical and morphological features, the predictive accuracy can be improved.

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.

Objective:To explore the diagnostic value of radiomics based on arterial-venous mixed images derived from dual-energy CT (DECT) data in diagnosis of cervical lymph nodes (LNs) metastasis of papillary thyroid cancer (PTC).Methods:From June 2017 to December 2018, eighty-four patients with preoperatively DECT scanning and pathologically confirmed PTC (129 non-metastatic LNs and 97 metastatic LNs) in the First Affiliated Hospital of Nanjing Medical University were included in this study. The clinical and imaging data of all patients were retrospectively analyzed. The training cohort consisted of 62 PTC cases with 156 LNs (91 non-metastatic LNs and 65 metastatic LNs). An independent validation cohort consisted of 22 PTC patients with 70 LNs (38 non-metastatic LNs and 32 metastatic LNs). Semi-automatic LNs segmentation was conducted on arterial-venous mixed images derived from DECT using Syngo.via Frontier Radiomics software. Totally 1 226 radiomics features were extracted from arterial-venous mixed images for each LN. The least absolute shrinkage and selection operator (LASSO) regression was applied for radiomics features selection and signature building. The logistic regression modeling was used to construct diagnostic models based on the CT image features of LNs (model 1), the radiomics signature (model 2) and the combination of the CT image features and radiomics signature (model 3). An intuitive nomogram was plotted for model 3. The ROC curve analyses and area under the curve (AUC) were performed to evaluate the diagnostic efficiency of the three models, with the performances compared using the Delong test.Results:Model 1 was developed with LNs shape, degree of enhancement, pattern of enhancement, calcification and extra nodal extension. Three arterial phase radiomics features were selected and used to establish radiomics signature using LASSO regression (model 2). Model 3 was developed with LNs size, shape, degree of enhancement and radiomics signature. In both the training and validation cohort, model 3 showed the best diagnostic performance (AUC=0.965, 0.933), followed by model 2 (AUC=0.947, 0.910), and both these two models significantly outperformed model 1 (AUC=0.850, 0.846) (training cohort, Z=4.066 and 3.758, P both<0.001; validation cohort, Z=2.871 and 1.998, P=0.017 and 0.042) respectively. Conclusion:The radiomics model based on arterial-venous mixed images derived from DECT data can realize effective diagnosis of LNs metastasis in patients with PTC; and the combination model of radiomics signature with CT image features can further improve the diagnostic accuracy.

Objective:To investigate the value of magnetization transfer imaging (MTI) and fat suppression T 2WI (FS-T 2WI) in predicting the clinical activity of Graves ophthalmopathy (GO). Methods:From October 2020 to July 2021, 64 GO patients were prospectively enrolled in the First Affiliated Hospital of Nanjing Medical University. According to the clinical activity score (CAS), the patients were divided into active group (CAS≥3, 39 patients and 78 eyes) and inactive group (CAS<3, 25 patients and 50 eyes). The coronal MTI and FS-T 2WI were scanned for pre-treatment assessment. Magnetization transfer ratio (MTR) of extraocular muscles, and signal intensity ratio (SIR) between extraocular muscles and temporalis were measured, respectively. The independent-sample t-test was used to compare the MTR and SIR between two groups. The correlations between MRI parameters and CAS were analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the value of each and combined parameters for predicting the clinical activity of GO. The DeLong test was used to compare the area under the curve (AUC). Results:The MTR of active group and inactive group were 0.45±0.04 and 0.51±0.04, respectively, the difference was statistically significant ( t=7.62, P<0.001). The SIR were 3.4±0.6 and 2.6±0.5, respectively, and the difference was also statistically significant ( t=-8.20, P<0.001). MTR was negatively correlated with CAS ( r=-0.46, P<0.001), while SIR was positively correlated with CAS ( r=0.63, P<0.001). The AUC of MTR, SIR and the combination of MTR and SIR for predicting the clinical activity of GO were 0.840, 0.845 and 0.905, respectively. The combination of MTR and SIR showed higher performance than MTR or SIR alone, and the differences were statistically significant ( Z=2.61, P=0.009; Z=2.15, P=0.032). Conclusions:The quantitative parameters of MTI and FS-T 2WI, namely MTR and SIR, can be used to evaluate the clinical activity of GO. Integrating MTI and FS-T 2WI can improve the diagnostic efficiency.