Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

Aim To investigate the effect of adenosine on the autophagy and proliferation of hepatocellular carcinoma cells, and improve the curative effect of a-denosine on hepatocellular carcinoma. Methods HepG2 cells were incubated with adenosine, CCK-8 method was used to study the changes of cell prolifera-tion,Western blot was used to study the expression of LC3-Ⅱ and LC3-Ⅰ, and MDC staining was used to observe the number of autophagosomes. Results HepG2 cells were incubated with adenosine(1.0~4.0 mmol·L-1) for 48 h,the proliferation of HepG2 cells were detected at the different time points (12,24,48 h),and the result showed the proliferation was signifi-cantly inhibited by adenosine (P < 0.01). HepG2 cells were incubated with adenosine (0.2,0.5,1.0, 2.0,4.0 mmol·L-1) for 24 h,the ratio of LC3-Ⅱ/LC3-Ⅰ decreased significantly in low concentration of adenosine group (0.2, 0.5 mmol·L-1, P <0.05;1.0 mmol·L-1,P<0.01),and the ratio of LC3-Ⅱ/LC3-Ⅰ increased significantly in higher concentration of adenosine group (4.0 mmol·L-1, P <0.05). HepG2 cells were incubated with adenosine(1.0 mmol·L-1) for 24 h, the ratio of LC3-Ⅱ/LC3-Ⅰ de-creased significantly at 6,12 and 24 h detecting point, the number of autophagosomes were reduced, the low-est ratio of LC3-Ⅱ/LC3-Ⅰ and autophagosomes were observed at 12 h detecting point(P<0.01). Conclu-sions Adenosine inhibits the proliferation of hepato-cellular carcinoma cells,the low concentration of aden-osine inhibits the autophagy,while the high concentra-tion of adenosine increases the autophagy, which is of great significance to reduce multi-drug resistance and improve the therapeutic effect of anti-hepatoma drugs.

Objective To evaluate the pharmacokinetics and safety of single micro dose in travenous temozolomidein Chinese health male volunteers or standard treatment in glioma patients.Methods 14 healthy subjects of phase 0 research were assigned to take a single microdose of 2 mg · m-2 intravenous temozolomide.24 glioma patients of phase Ⅰ research were assigned to take 150 mg · m-2 intravenous temozolomide.These rumconcentrations of temozolomide were assayed with LC-MS/MS.Results Fourteen healthy subjects pharmacokinetic parameters wereCmax (0.14 ± 0.03) μg · mL-1,tmax (80.40 ± 12.60) min,t1/2 (114.00±6.00) min,AUC0-24h (25.80 ±4.72) μg · mL-1 · min,AUC0-x (26.20 ±4.79) μg · mL-1 · min.Twenty-one glioma patients were included in the pharmacokinetic analysis,pharmacokinetic parameters were Cmax (7.92 ± 1.50) μg · mL-1,tmax (87.90 ± 5.38) min,t1/2 (108.00 ± 5.25) min,AUC0-24h (1530.00 ±270.00) μg · mL-1 · min,AUC0-∞ (1550.00 ±273.00) μg · mL-1 · min.All the 14 healthy volunteers and 24 glioma patients were included in the safety analysis.No adverse events were detected in health volunteers.6 gliomapatients experienced 7 adverse events related to temozolomide.There were no serious adverse events in two early clinical reseach.Conclusion Pharmacokinetic parameters of phase 0 research of intravenous temozolomide reflected the characteristics of the drug distribution and elimination in some extent.It is significative to follow-up clinical trials.

Objective To evaluated the pharmacokinetics and safety of single microdose imatinib mesylate in Chinese health volunteers.Methods Eight subjects were randomly assigned to take orally a single microdose of 4 mg imatinib mesylate.The serum concentrations of ima-tinib were assayed with LC-MS/MS.Results The following pharmaco-kinetic parameters were calculated by WinNolin 6.3 software.Cmax (12.70 ±6.61 ) ng · mL-1, tmax ( 1.94 ±0.94 ) h, AUC0-24 h (90.10 ±37.70)ng· mL-1· h, t1/2 ( 10.40 ± 5.01 ) h, CL/F (47.20 ±33.40)L· h-1, V/F ( 541.00 ± 128.00 ) L, MRT (7.21 ±1.30)h.No adverse events and serious adverse events were detected.Conclusion Pharm-acokinetic parameters of phase 0 research of imatinib mesylate reflected the characteristics of the drug distribution and elimination in some extent.It was significant to protect subjects in phase 0 research by taking microdose imatinib mesylate.

OBJECTIVETo assess the role of small ubiquitin-like modifier 4 (SUMO4) gene polymorphisms (rs237025, rs237024 and rs600739) in the susceptibility to coronary artery disease (CAD) with and without type 2 diabetes mellitus (T2DM) in Chinese Han ethnic population in Beijing.

METHODSIn this case-control study, 558 subjects with angiography-proven CAD were divided into two groups according to the WHO 1999 criteria: 369 with normal glucose tolerance (CAD group) and 189 with T2DM (T2DM+ CAD group). Meanwhile 500 healthy subjects free of T2DM and CAD were selected as normal controls (control group). Allelic and genotypic distributions of the three single nucleotide polymorphisms (SNPs) were determined with polymerase chain reaction-high resolution melting curve (PCR-HRM) and gene sequencing. Clinical and biochemical data were compared among carriers of different genotypes through a stratified analysis.

RESULTSNo significant difference was found in the distribution of genotypes and alleles of each SNP between different groups (P> 0.05). Nevertheless, stratified analysis indicated a significant difference in plasma triglycerides (rs237025) and body mass index (rs600739) among individuals of different genotypes from the T2DM+ CAD group (P= 0.020 and P= 0.049, respectively). Multiple comparison also indicated that GG genotype of rs237025 had a higher level of plasma triglycerides than AA genotype (P< 0.01).

CONCLUSIONNo association between SUMO4 gene polymorphisms and CAD with and without T2DM was detected. Such polymorphisms may not be a risk factor for Chinese Han ethnic patients in Beijing.

Aged ; Case-Control Studies ; Coronary Artery Disease ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Small Ubiquitin-Related Modifier Proteins ; genetics

OBJECTIVETo investigate CT findings and incidence rate of gastric bare area involvement (GBAI), left adrenal gland involvement (LAGI) and perirenal space involvement (PSI) in acute pancreatitis, and to also explore the value of these appearances in predicting complications and mortality of patients.

METHODSCT imaging data of 575 patients with AP diagnosed by clinic from October 2009 to April 2011 were analyzed retrospectively. There were 339 male and 236 female patients, aging from 16 to 93 years with a mean of (51 ± 16) years. Involvement with or without gastric bare area, left adrenal gland, perirenal space were focused, and the relationship were analyzed between these CT findings and complications and mortality of patients.

RESULTSAmong 167 patients (29.0%) with GBAI, 132 had complications and 16 died. The sensitivity and specificity of GBAI for predicting complications were 45.4% and 87.7%, respectively, and 84.2%and 72.8% for predicting mortality. In all 107 patients (18.6%) with LAGI, 81 had complications and 18 died. The sensitivity and specificity of LAGI for predicting complications were 27.8% and 90.8%, respectively, and 94.7% and 84.0% for predicting mortality. Among 335 patients (58.3%) with PSI, 201 had complications and 19 died. The sensitivity and specificity of PSI for predicting complications were 69.1% and 52.8%, respectively, and 100% and 43.2% for predicting mortality. Of all patients, 210 (36.5%) owned two or more positive CT findings among GBAI, LAGI, and PSI. One hundred ninety-eight of these patients had complications and 19 died, that predicted the sensitivity and specificity for complications were 68.0% and 95.8%, respectively, and 100% and 65.6% for mortality. The risk of complications in the patients with GBAI or LAGI was increased than normal gastric bare area or left adrenal gland 5.9 or 3.8 times respectively, and the risk of death was improved 14.3 or 94.5 times respectively. The risk of complications in those patients with two or more positive findings increased by 48.3 times. By analyzing receiver operating characteristic (ROC) curve, the combination of GBAI, LAGI, and PSI was the best way to predict the complications of AP. The area under the ROC was 0.819.

CONCLUSIONSThe CT imaging could effectively indicate the signs of GBAI, LAGI and PSI of AP. The GBAI. LAGI and PSI were related with the severity and prognosis of AP, and these findings could be clinical indicators for evaluating prognosis of AP.

Acute Disease ; Adolescent ; Adrenal Glands ; diagnostic imaging ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney ; diagnostic imaging ; Male ; Middle Aged ; Pancreatitis ; complications ; diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Stomach ; diagnostic imaging ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo compare with the clinical applications of routine-subtraction and dual-energy subtraction cervical arteries computed tomographic angiography (CTA) for cervical arteries imaging.

METHODSScanning was performed in 45 patients with clinically suspected cervical arteries disease with dual-source CT. The data of two different energy were collected only at one scanning. The data post processing include: conventional bone-removal digital subtraction (routine-subtraction) was performed with plain and 80 kV enhanced scanning. Volume render (VR) and maximum intensity projection (MIp) reconstruction were finished. Direct bone-removal digital subtraction (dual-energy subtraction) was performed with 80 and 140kV enhanced scanning that have different energy, and saving the data of subtraction. VR and MIp reconstruction were finished. The image quality, which was divided into four grades, was compared between these two groups. The effective radiation dose was also compared.

RESULTSFor normal vessels, no abnormality was found in 24 of 45 cases, with the common carotid artery and its branches clearly displayed with both two methods. The image quality was not significantly different between dual-energy subtraction CTA and routine subtraction CTA (P>0.05) . For stenotic vessels, 45 stenotic vessels in 21 cases were clearly displayed clearly with both two methods (P>0.05) . The effective radiation dose was decreased by 17.3 % for dual-energy subtraction CTA when compared with routine-subtraction CTA (P<0.01) .

CONCLUSIONSBoth routine-subtraction and dual-energy subtraction CTA can clearly display normal and stenotic vessels. The radiation exposure dose is relatively lower in dual-energy CTA. The dual-energy subtraction CTA has better effectiveness when used for non-cooperation patients.

Adult ; Aged ; Aged, 80 and over ; Angiography, Digital Subtraction ; methods ; Carotid Artery Diseases ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Radiation Dosage ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; methods

Objective To evaluate the accuracy of dual-source CT coronary angiography (DSCTCA) for the depiction of functionally relevant coronary artery lesion ( FRCAL) , by using myocardial perfusion imaging (MPI) with single photon emission computed tomography(SPECT). Methods DSCTCA,99Tcm-MIBI SPECT myocardial perfusion imaging (MPI) and conventional coronary angiography (CCA) were performed in 59 patients with clinical suspected CAD . Coronary artery diameter narrowing of 50% or greater at DSCTCA was defined as stenosis and was compared with MPI findings. CCA was served as a reference standard for DSCTCA. Results (1) Agreement between DSCTCA and CCA was good (kapaa = 0.93 for patient-based analysis, Kappa = 0. 88 for vessel-based analysis) . (2) DSCTCA revealed stenoses in 86 segments corresponding to 60 arteries in 34 patients. (3) MPI revealed 19 reversible,21 partially reversible, and 5 fixed defects in 25 patients. (4) About 65.0% (39/60) of all the narrowed coronary arteries were determined to be FRCAL Sensitivity, specificity, accuracy, positive predictive values and negative predictive values, respectively, of DSCTCA in the detection of all MPI defects were 92.0%, 67.6%, 78.0%, 67. 6% and 92. 0% on a per-patient basis and 86. 7% , 89. 0% , 88. 6% , 65. 0% and 96. 6% on a perartery basis. (5) ROC analysis showed that predictive value of DSCTCA in FRCAL was similar with those of CCA (AUCs = 0. 80, 0. 82). Conclusions DSCTCA can evaluate FRCAL indirectly. When DSCTCA results are negative,it can help ruled out patients with FRCAL The positive DSCTCA results should combin MPI in predictor of myocardial ischemia.

OBJECTIVE: To explore the value of transthoracic echocardiography (TTE) in transcatheter closure of atrial septal aneurysm (ASA) combined with secoundum-type atrial septal defect (ASD). METHODS: Fourteen patients (3 males and 11 females) who had ASA combined with secoundum-type ASD were diagnosed by TTE or transesophageal echocardiography. The ASA projected to the right atrium in all patients. The width of basilar part was 13 approximately 24 (18.5+/-3.9) mm, and the vertical extent was 7 approximately 11(9.7+/-1.8) mm. Ten patients combined with single hole ASD and 4 patients with multiple hole ASD. Blood shifting from the left atrium to the right atrium was displayed in color Doppler in all patients. All patients were treated by transcatheter closure under the guiding of X fluoroscopy and TTE, and examined with TTE during the follow-up. RESULTS: Transcatheter closure was successfully performed by 14 occluders in all patients. No residual shunt was detected immediately by TTE after the procedure in all patients. During the 6 approximately 12 month follow-up, no residual shunt or occluder shifting was found, the dimensions of the heart became normal in 11 patients (79%) and were significantly decreased in 4. CONCLUSION Transcatheter closure is feasible in patients with ASA combined with secoundum-type ASD, and extra attention must be paid to the specialty. TTE is very important in case selection before transcatheter closure, and it may be used to monitor and guide the procedure during transcatheter closure.
Adult ; Atrial Septum ; Balloon Occlusion ; methods ; Cardiac Catheterization ; Echocardiography ; Female ; Heart Aneurysm ; complications ; therapy ; Heart Septal Defects, Atrial ; complications ; therapy ; Humans ; Male ; Middle Aged ; Ultrasonography, Interventional ; Young Adult