Positive rate and accuracy of ultrasound-guided fine-needle aspiration cytology for detecting suspected thyroid carcinoma nodules of different sizes / 南方医科大学学报

OBJECTIVE@#To analyze the accuracy and positive rate of ultrasound-guided fine-needle aspiration (US-FNA) cytology for detecting suspected thyroid cancer nodules of different sizes.@*METHODS@#A total of 591 patients with 594 suspected malignant thyroid nodules received examinations with US-FNA cytology. Based on their size, the nodules were divided into group I (4-5 mm), group II (6-10 mm), group III (>10 mm). With the results of pathology as the standard, we analyzed the results of US-FNA cytology for detecting thyroid carcinoma in terms of its accuracy, indeterminate rate, positive predictive value and negative predictive value for nodules of different sizes.@*RESULTS@#The positive rates in group I, group II and group III were 39.2% (40/102), 48.2% (172/357) and 65.2% (88/135), respectively, similar between groups I and II (=0.107) and differed significantly between groups I and III (=0.000) and between groups II and III (=0.001). The accuracy, indeterminate rate, positive predictive value and negative predictive value in the 3 groups were 95.5% (21/22), 97.1% (100/103), and 94.4% (51/54); 2.9% (3/102), 2.8% (10/357), and 1.5% (2/135); 100%, 100%, and 98%; 66.7%, 57.1%, and 33.3%, respectively, showing no significant differences among the 3 groups.@*CONCLUSIONS@#The size of the thyroid nodules can affect the positive rate but does not have significant effects on the accuracy, indeterminate rate, positive predictive value or negative predictive value of US-FNA cytology.

Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.

Study on 99 Tcm-3P4-RGD2 microSPECT/CT imaging to anti-angiogensis therapeutic effect / 中华放射医学与防护杂志

Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy .Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice.Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group . MicroSPECT/CT imaging was performed with 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-3P4-RGD2 , expressed as percentage of injected dose (%ID) or %ID per gram (%ID/g) were measured and calculated based on microSPECT/CT.Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point .Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration ( t=5.81, P0.05).The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration ( t=10.48, P<0.05), and it decreased to a value less than control ( t =3.26, P <0.05) at 3 d after Avastin administration and continually reduced at longer time after administration .PC-3 tumor had less uptake of 99 Tcm-3P4-RGD2 in both Avastin administration group and its control group .The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel .Linear relationship was verified between tumor uptake (%ID/g ) and integrin β3 expression (y=0.499 1x-0.243 8, R2 =0.811 7).Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .

Experimental study on microSPECT-CT bremsstrahlung imaging in solid tumor mesenchymal implantation of 32 P-chromic phosphate-paclitaxel-poly-L-lactic acid sustained-release seeds / 重庆医学

Objective To investigate the value of single photon emission computed tomography (CT) imaging and transmis‐sion CT imaging (microSPECT‐CT ) bremsstrahlung imaging for the solid tumor mesenchymal implantaion of 32 P‐chromic phos‐phate‐paclitaxel‐poly‐L‐lactic acid (32 P‐CP‐PSP‐PLLA) sustained release seeds and to investigate the 32 P in vivo biodistribution and degradation sustained release churacteristics .Methods The animal model of prostate cancer subcutaneously transplanted tumor was established .32 P‐CP‐PSP‐PLLA sustained‐release seeds were intratumorally implanted by the mediation of microSPECT‐CT brems‐strahlung imaging and the 32 P distribution in bearing tumor mouse was verified by the imaging and biological distrubtion tests .The ultrastructural changes of 32 P seeds were observed by the scanning electron microscope .Results The MicroSPECT/CT brems‐strahlung imaging could effectively guide the intratumoral implantation operation of the 32 P sustained‐release seeds with clear visu‐alization .Partial sustained‐release 32 P was remained in the tumor tissues with little distribution in important organs of spleen and liver ,which was proved by the biodistribution results .The particle surface and inside micropores and tunnels formation ,their pro‐gressive increase ,fusion and connection were found by the electronic microscope after the 32 P sustained‐release seeds intratumoral implantation .Conclusion The MicroSPECT/CT bremsstrahlung imaging can effectively monitor the 32 P sustained‐release seeds and their in vivo biodistribution and lays a foundation for the sustained‐release seeds prostatic targeted implantation .

Study of microSPECT-CT imaging of mice orthotopic glioma with 99Tcm-Galacto-RGD2 / 中华放射医学与防护杂志

Objective To investigate the synthesis, in vivo biodistribution of 99Tcm-HYNIC-PEG4-E[PEG4-c (RGDfk)] 2 (99 Tcm-Galacto-RGD2), and its potential usage for targeted imaging of mice orthotopic glioma.Methods 99Tcm-Galacto-RGD2 was synthesized straightforward and its radiochemical purity and stability and distribution in mice were analyzed.MicroSPECT-CT imaging was done in a mice orthotopic glioma model, which had been set up with U87MG cells, after administration of 99Tcm-Galacto-RGD2.Region of interest (ROI) of glioma was drawn on SPECT-CT section images to quantify tumor uptake (％ ID/cm3).Glioma was harvested for pathological examination.Linear-regression was used to analyze the relationship between integrin αvβ3 and tumor uptake (％ID/cm3).Results The radiochemical purity of 99Tcm-Galacto-RGD2 was (97.7 ±0.8)％ and stable in vitro.Hynic-Galacto-RGD2 could specifically bind to integrin αv β3 of tumor cells with a IC50 of (18 ± 3) nmol/L.After tail vein injection, 99Tcm-Galacto-RGD2 was rapidly discharged from the blood, liver, kidneys and had a relative low concentration in normal brain tissue.MicroSPECT-CT imaging demonstrated that, after 60 min of injection, this drug was well uptaken by glioma tumor than that after 30 min (t =7.13 ,P ＜0.05), and the tumor to normal brain tissue (T/B) uptake ratio of 99Tcm-Galacto-RGD2 was 13.92± 3.43.Injection of HYNICGalacto-RGD2 2 min prior to 99Tcm-Galacto-RGD2 injection extensively reduced the uptake of radioactive drug in tumor tissue (t =11.36, P ＜ 0.05).Bland-Altman analysis showed that tumor volume based on SPECT-CT imaging measurement had almost same value with the tumor reference volume (95％ CI =-11.94％-11.92％).In addition, the tumor uptake of 99Tcm-Galacto-RGD2 and cellular integrin αvβ3 expression level had a linear relationship (R2 =0.896).Conclusions Stable 99Tcm-Galacto-RGD2 can be synthesized easily and is applicable for microSPECT-CT imaging analysis of orthotopic glioma in mice together with the evaluation of integrin αvβ3 level in tumor.

Retrograde subintimal angioplasty for treatment of occlusive diseases in the long segment of the infrapopliteal artery / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the clinical efficacy of retrograde puncture subintimal angioplasty (SIA) for treatment of occlusive diseases in the long segment of the infrapopliteal artery.</p><p><b>METHODS</b>The clinical data of 50 patients with occlusive diseases in the long segment of the infrapopliteal artery were retrospectively analyzed. The patients were divided into control group (n=25) and study group (n=25) and received antegrade SIA and retrograde puncture SIA with long balloon after the failed antegrade SIA, respectively. The ankle brachial index (ABI) and the temperature of the infrapopliteal skin before and after the operation were compared between the two groups.</p><p><b>RESULTS</b>The technical success rate was 100% in the 50 patients, who showed obviously improved ischemic symptoms without serious complications. The ABI of the study group increased from 0.31 ± 0.12 before the treatment to 0.47 ± 0.09 at 24 h, 0.56 ± 0.06 at 1 week, 0.63 ± 0.07 at 3 months, 0.58 ± 0.06 at 6 months, and 0.49 ± 0.03 at 12 months after the treatment, and the skin temperature increased from 28.13 ± 2.45 before the operation to 33.87 ± 1.24, 34.16 ± 0.44, 34.19 ± 0.25, 32.45 ± 0.25, and 31.05 ± 0.21 at the corresponding time points after the treatment, respectively, showing significant improvements after the operation (P<0.05). ABI, skin temperature and the patency rate were similar between the two groups at each of the postoperative time points (P>0.05).</p><p><b>CONCLUSION</b>Retrograde puncture SIA is safe and effective for treatment of arteriosclerosis obliterans in the infrapopliteal arteries with a high clinical success rate and a low complication rate after the failure of antegrade SIA.</p>

Expressions of interferon-inducible genes in patients with systemic lupus erythematosus and their assoc-iation with disease activity / 中华风湿病学杂志

Objective To investigate the expression levels of interferon-inducible genes (IFIT1,IFIT4,OAS1,OASL,ISG15) in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus(SLE).and the relations between these genes expression levels and disease activity are explored.Methods Sybr green dye based real-time quantitative PCR method was used to detect the expression levels (indicated as-△△Ct value) of WIT1,IFIT4.OAS1,OASL and ISG15 in 76 patients with SJJE and 54 controls.Their expression levels were compared with erythroeyte sedimentation rate (ESR),serum C reactive protein (CRP),complement C3,C4.antinuclear antibody (ANA).anti-double stranded DNA antibody.The associations between the expression levels of IFIT1,IFIT4,OASI.OASL,ISG15,ESR,CRP,complement C3,C4,ANA,anti-double stranded DNA antibody and SLEDAI scores in patients with SLE were analyzed.Results ① The expression levels of WIT1,IFIT4,OAS1,OASL and ISG15 in the SLE patients were significantly higher than those of the normal controls (P＜0.01).The expression levels of IFIT1,IFIT4,OAS1,OASL and ISG15 in active SLE patients were higher than those of inactive SLE patients (P＜0.05).The real time expression levels of IFIT1,IFIT4,OAS1.OASL and ISG15 showed positive correlations with each other (r＞0.5,P＜0.05) in patients with SLE.② The expression levels of IFIT1,IFIT4,OAS1,OASL and ISG15 were positively correlated with the SLEDAI scores (r＞0.5,P＜0.05).③ There was no correlation between ESR,CRP,complement C3,C4,ANA and the expression levels of IFIT1,IFIT4,OAS1,OASL,ISG15,SLEDAI scores except anti-double stranded DNA antibody (r＞0.5.P＜0.05).Conclusion The expression levels of IFIT1,IFIT4,OAS1,OASL and ISG15 in patients with SLE are significantly higher than those of the normal controls,and positively associated with SLEDAI scores,so they are helpful in evaluating SLE disease activity and severity.IFIT1,IFIT4,OAS1,OASL and ISG15 genes may be the potential treating targets for SLE.

The utility of ~(99m)Tc-Sandostatin somatostatin receptor imaging in the evaluation of lung cancer / 医学研究生学报

Objective: To determine the noninvasive imaging efficacy of 99mTc-sandostatin scintigraphy for lung cancer. Methods: 57 consecutive patients with pulmonary nodules(PN) were studied with 99mTc-sandostatin scintigraphy.Planar imaging was obtained after injection of (991.6?187.59) MBq of 99mTc-sandostatin at 1.5-4 hour with GE Dual-head gamma camera(Millennium VG, Hawkeye ;General Electric Medical Systems) . SPECT images of the chest were performed at 4-6 h post injection. All scintigraphically detected lesions were confirmed by histopathological analysis and/or by other imaging modalities.Tumor to normal tissues ratios (T/N) were calculated . Results: Out of 57 patients ,47 were malignant tumors; 12 with small cell lung cancer (SCLC), 35 with non- small cell lung cancer (NSCLC). 10 had benign lesions. The sensitivity , specificity and accuracy of 99mTc-Sandostatin in detection of lung cancer were 95.7%, 90%, 94.7%, respectively. In two patients (pts) with pulmonary squamous cell cancer 99mTc-Sandostatin imaging was false negative. In 10 pts. with benign PN, 9 pts. was true negative, but one patient with tubercolama was false positive. T/N ratio was 3.43?0.66, 2.24?0.31 in SCLC and NSCLC respectively. The T/N ratio was higher in small cell lung cancer than NSCLC(t = 4.072 ,P

Influences on Serum Insulin and Glucose by Different Fasting Time in Alloxan Diabetic Mice / 中国药科大学学报

AIM　The purpose is to study the influences on serum insulin and glucose by different fasting time in alloxan (ALX)-induced diabetic mice. METHODS　Normal mice of serum glucose were determined at different fasting time. According to different fasting time (0 h, 6 h, 12 h, 18 h and 24 h), mice were divided into 5 diabetic experimental model (DEM) groups induced by ip ALX 200 mg/kg and 1 control group. Serum glucose (SG) and body weight were determined at experimental d0, d3, d8 and d13 and serum insulin concentration (SIC) at experimental d13. The death rate and succeeding rate were also observed during experimental time. RESULTS　Along with prolonged fasting time, SG、death rate and succeeding rate were increased in DEM mice, SG of normal mice, and SIC and body weight of DEM mice were decreased. Results showed that the optimal fasting time of ALX-induced diabetic mice was 12～18 h a lower death rate and impairment to pancreatic islets. Fasting 18h diabetic mice had higher succeeding since during this time rate、lower death rate and longer hyperglycemia time. CONCLUSION　This study indicated SG of mice in vivo had a protective effect against impairment action of pancreatic islets by ALX.

Changes in the expression of endothelin system in rats with chronic heart failing / 中国病理生理杂志

AIM: To study the changes of endothelin system during chronic heart failure (CHF) and imply the relationship between endothelin system and the course of CHF by observing the mRNA expression of endothelin receptors (ET_AR and ET_BR) and PreproET_1 in early stage and later stage of CHF caused by left coronary artery ligation. METHODS: The mRNA expression of ET_A, ET_B receptors and PreproET_1 were detected by RT-PCR technique. The plasma concentrations of ET_1 and ANP were determined by RIA method. RESULTS: The plasma concentrations of ET_1 and ANP, and the mRNA expression of ET receptors and PreproET_1 in the lefe ventricle increased significantly in early stage (myocardial infarction 10 d). While the plasma concentrations of ET_1 and ANP in later stage (myocardial infarction 70 d) were higher than those in the early stage. However, the mRNA expression of ET_AR, ET_BR and PreproET_1 decreased significantly. The mRNA expression of ET_AR in myocardial infarction (MI) 70 d rats had no difference with those in sham-operated rats, and the mRNA expression of ET_BR and PreproET_1 in MI 70 d rats was lower significantly than those in MI 10 d rats, but significantly higher than those in sham-operated rats. CONCLUSION: The changes of ET receptors and PreproET_1 mRNA expression are involved in the cardiac function modulation during the different stages in chronic heart failure. [