An open-label, randomized, multicentre phase II/III trial (ZGDH3) has demonstrated that compared with sorafenib, donafenib significantly prolonged the overall survival (OS) of patients with advanced hepatocellular carcinoma (HCC). It also showed a better survival benefit than sorafenib in the prespecified subgroup analysis. This article aimed to further explore whether the baseline characteristics of patients other than the predefined subgroups were related to the better OS benefit of donafenib.

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 (P=0.107) and differed significantly between groups I and III (P=0.000) and between groups II and III (P=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.

BACKGROUND:The measurement of plasma catecholamines (CAs) including dopamine (DA), epinephrine (E), and norepinephrine (NE) and their derivatives including metanephrine (MN), normetanephrine (NMN), vanillylmandelic acid (VMA), and homovanillic acid (HVA) has been used in the diagnosis of pheochromocytoma and paraganglioma (PPGL) and primary hypertension (PH) but are typically detected individually when clinical testing. In this study, pre-column derivatization with dansyl chloride (DNS-Cl) combined with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously quantify HVA, VMA, MN, NMN, DA, E, and NE in the plasma from patients with PPGL and PH.METHODS:Plasma samples were extracted by acetonitrile and derivatized with DNS-Cl, followed by reverse phase separation and triple quadruple detection. Quantification of the CAs and their derivatives in 10 PPGL, 10 PH, and 100 healthy subjects was performed by UPLC-MS/MS analysis.RESULTS:All the values of detected CAs/derivatives were in the linearity ranges of the fitted curves. The expression levels of the seven CAs in the PPGL and PH patients were significantly higher than the healthy controls, suggesting increased CA production in the former. There were significant differences in plasma NE, NMN, and VMA levels between the PPGL and PH patients, but there was no significant difference in plasma E, MN, DA, and HVA. A discriminant analysis showed that 90% of the final cases were classified correctly based on the detected CAs/derivatives.CONCLUSIONS:Our results show that the combined detection of the seven CAs/derivatives could be used for the clinical diagnosis of PPGL and PH.

Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced or metastatic gastric cancer (GC) in China. We performed a real world study to observe the current status, efficacy and safety of apatinib treatment in clinical practice, and preliminarily define patients (pts) who could benefit from apatinib. Methods: From September 2017, pts (age ≥18 yrs) with pathologically or histologically diagnosed GC who were given apatinib treatment met the inclusion criteria. The target sample size is 1000. Results: As of April 2018, 651 pts from 37 centers were eligible. There are 491 (75.4%) males and 160 (24.6%) females. The median age was 62.5 yrs. The majority pts were at stage IV (399, 61.3%), had prior surgery (370, 56.8%) and chemotherapy (341, 52.4%). Pts with ECOG PS 0–2 were 520 (79.9%), and ECOG PS 1 was most common (403, 61.9%). Metastases were detected in 370 (56.8%) pts, which mainly were hepatic and pulmonary metastases. Pts received apatinib monotherapy or in combination with chemotherapy. The dose of apatinib in most pts (70.0%) was 500 mg qd. Apatinib was used in perioperative treatment for 269 (41.3%) pts. 382 (58.7%) pts with unresectable locally advanced, recurrent, or metastatic disease received apatinib as different lines of systemic therapy; among whom, 284 pts were evaluable for response, and 113 pts obtained complete clinical efficacy and safety assessment. 12 achieved partial response, 79 had stable disease and 22 got progressive disease. Thus, the objective response rate (ORR) and disease control rate (DCR) were 10.6% and 80.5%. 78.8% pts reported adverse events (AEs). The incidence of grade 3-4 AEs was 22.1%. Main apatinib-related AEs were hypertension (20.3%), and hand-foot syndrome (26.5%). There were tendencies showed that prognostic factors related with higher ORR were lines of apatinib (≤2, 11.3%; >2, 9.5%) and duration of medication (< 90 days, 7.1%; 90-120 days, 6.7%; >120 days, 11.9%). Conclusions: In the real world, GC pts receiving apatinib therapy are mainly elderly men, stage IV, and ECOG PS 1. Apatinib is confirmed to be effective and safe for GC pts. Further analysis is needed to identify pts who obtain benefits from apatinib treatment. Clinical trial identification: NCT03333967. Legal entity responsible for the study: The First Affiliated Hospital of Anhui Medical University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Objective. To synthesize 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) with a synthesis module and investigate PET-CT imaging to monitor PSMA expression during prostate cancer (PCa) progression and tumor growth in mice bearing subcutaneous PCa xenografts. Method. The radiochemical purity and stability of 68Ga-PSMA-11 were determined via radio-HPLC. The PCa cell lines of different PSMA expression levels (PC3, VCAP±, CWR22RV1+, and LNCaP++) were selected to mimic the PCa progression. 68Ga-PSMA-11 biodistribution was studied by dissection method and in vivo imaging with micro PET-CT. The expression levels of PSMA in tumor cells and tissues were analyzed by immunofluorescence, flow cytometry, and western blot. The correlation between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results. The radiochemical purity of 68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2 h. The equilibrium binding constant (Kd) of 68Ga-PSMA-11 to LNCaP, CWR22Rv1, PC-3, and VCAP cells was 4.3 ± 0.8 nM, 16.4 ± 1.3 nM, 225.3 ± 20.8 nM, and 125.6 ± 13.1 nM, respectively. Results of tumor uptake (% ID and % ID/g or % ID/cm3) of 68Ga-PSMA-11 in biodistribution and micro PET imaging were LNCaP > CWR22RV1 > PC-3 and VCAP due to different PSMA expression levels. It was confirmed by flow cytometry, western blot, and immunofluorescence. Tumor uptake (% ID/cm3) of 68Ga-PSMA-11 increased with the tumor anatomical volume in quadratic polynomial fashion and reached the peak (when tumor volume was 0.5 cm3) earlier than tumor uptake (% ID). Tumor uptake (% ID/cm3) of 68Ga-PSMA-11 based on functional volume correlated well with the PSMA expression in a linear manner (y=9.35x+2.59, R2=0.8924, and p<0.0001); however, low dose 2-PMPA causes rapid renal clearance of increased tumor/kidney uptake of 68Ga-PSMA-11. Conclusions. The 68Ga-PSMA-11 PET-CT imaging could invasively evaluate PSMA expression during PCa progression and tumor growth with % ID/cm3 (based on functional volume) as an important index. Low dose 2-PMPA preadministration might be a choice to decrease kidney uptake of 68Ga-PSMA-11.

The traditional median filtering method uses a fixed filter window size method to remove the impulse noise in a fingerprint image. If the filtering window size is small, the traditional median filtering method will not filter out the impulse noise completely. If the filtering window size is large, the fingerprint image may become blurred. To solve the problem, a method based on adaptive median filter is proposed for fingerprint image enhancement processing and impulse noise removal in the paper. The use of adaptive median filtering to remove the impulse noise of the fingerprint image mainly involves three steps. First, the size of the adaptive median filter window is initialized, and it is judged whether the center pixel of the filter window in the fingerprint image is impulse noise. Second, the size of the filter window is determined based on the median value, the maximum value, and the minimum value within the filter window. Finally, median filtering is performed on the fingerprint image under the filter window size obtained in the previous steps, and the filter output value is used instead of the window center pixel value. The method is tested on rolled fingerprint images contaminated by impulse noise and fingerprint images contaminated by impulse noise from a crime scene. Experimental results show that the method based on adaptive median filter for fingerprint image enhancement outperforms the traditional median filtering method in filtering impulse noise performance.

32P high-dose rate brachytherapy allows high-dose radiation delivery to target lesions with less damage to adjacent tissues. The early evaluation of its therapeutic effect on tumours is vital for the optimization of treatment regimes. The most commonly used 32P-CP colloid tends to leak with blind therapeutic area after intratumour injection. We prepared 32P-chromic phosphate-polylactide-co-glycolide (32P-CP-PLGA) seeds with biodegradable PLGA as a framework and investigated their characteristics in vitro and in vivo. We also evaluated the therapeutic effect of 32P-CP-PLGA brachytherapy for glioma with the integrin αvβ3-targeted radiotracer 68Ga-3PRGD2. 32P-CP-PLGA seeds (seed group, SG, 185 MBq) and 32P-CP colloid (colloid group, CG, 18.5 MBq) were implanted or injected into human glioma xenografts in nude mice. Scanning electron microscopy (SEM) of the seeds, micro-SPECT imaging, and biodistribution studies were performed at different time points. The tumour volume was measured using a caliper, and 68Ga-3PRGD2 micro-PET-CT imaging was performed to evaluate the therapeutic effect after 32P intratumour administration. The delayed release of 32P-CP was observed with biodegradation of vehicle PLGA. Intratumoural effective half-life of 32P-CP in the SG (13.3 ± 0.3) d was longer than that in the CG (10.4 ± 0.3) d (P < 0.05), with liver appearance in the CG on SPECT. A radioactivity gradient developed inside the tumour in the SG, as confirmed by micro-SPECT and SEM. Tumour uptake of 68Ga-3PRGD2 displayed a significant increase on day 0.5 in the SG and decreased earlier (on day 2) than the volume reduction (on day 8). Thus, 32P-CP-PLGA seeds, controlling the release of entrapped 32P-CP particles, are promising for glioma brachytherapy, and 68Ga-3PRGD2 imaging shows potential for early response evaluation of 32P-CP-PLGA seeds brachytherapy.

目的 分析南京地区女性不同基因型HPV的感染情况和分型特点.方法 收集门诊9515例女性宫颈脱落细胞标本,采用PCR--导流杂交法对标本行21种HPV基因分型检测,包括高危型15种(16、18、31、33、35、39、45、51、52、53、56、58、59、66、68型)和低危型6种(6、11、42、43、44、CP8304型),分析感染率和基因型分布.结果 HPV感染率:20～29岁为29.43％(407/1383),30～39岁为26.16％(741/2833),40～49岁为25.23％(809/3207),≥50岁为27.90％(565/2025).HPV总感染率为26.80％;其中,高危型HPV感染率为23.71％,低危型HPV感染率为6.34％.HPV感染的前5位基因型分别为52、16、58、CP8304和53型.单一基因型HPV感染率为18.43％,前5位的基因型分别为16、52、58、CP8304和53型.混合基因型HPV感染率为8.37％,前5位的基因型组合为16+52型、52+CP8304型、52+53型、53+58型和16+58型.结论 南京地区女性21种基因型HPV感染率为26.80％,主要HPV感染基因型为52、16、58、CP8304和53型.

Objective To verify the performance characteristics of the human SLCO1B1 & APOE gene detection kit (PCR-fluorescent probe technique).Methods The verification protocol for the human SLCO1B1 & APOE gene detection kit manufactured by Wuhan YZY Medical Science and Technology Co.,Ltd.was designed by referring to the requirements of professional standard and pertinent literatures,and its accuracy,specificity,lowest detection limit and anti-interference ability were compared with those of sequencing technique (gold standard).Results The results coincidence of 20 clinical samples from fluorescence PCR and sequencing technique was 100％,which met the requirement of accuracy.Forty clinical samples with wild type loci determined by fluorescence PCR were verified by sequencing and no any mutation was detected,which met the requirement of specificity.The lowest detection limit of the kit was 10 ng/μL.Three interfering substances,including hemoglobin,bilirubin and triglyceride,were individually added into the blood samples with known genotype,and the results determined by the kit were coincident with that without interfering substances,which met the requirement of anti-interference ability.Conclusion The verification parameters of the human SLCO1B1 & APOE gene detection kit are basically consistent with the manufacturer's statement,indicating that the kit meets the requirements of the relevant quality management and may be applied to the detection of clinical samples.

Objective This paper aims to propose a novel method of ROI extraction which was used in renal dynamic imaging. Methods A total of 30 clinical dynamic renograms were introduced. The renal image was initially performed by morphological reconstruction followed by intensity-pair and Gaussian smoothing filter, which could sharpen the edge of kidney and suppress the noise. Then, adaptive Otsu threshold method was applied to segment the rough renal area. Finally, the morphological operation and boundary tracking were adopted to remove the irrelevant parts and extract the contour of renal. Results There was high correlation between physicians' manual contours and these by our approach. For area error analysis, the mean true positive area overlap, the mean false negative, the mean false positive and the boundary error were 91%, 13.4%, 9.3% and 1.6 pixels, respectively. Our approach acquired larger Dice index (0.9061±0.0196) and lower computing time (2.1477±0.2835) s than other methods. Conclusion The proposed method is a feasible approach for ROI extraction in renal dynamic imaging, which can obtain more efficient, accurate and robust results.

The current study aimed to investigate whole-brain three-dimensional arterial spin labeling imaging (3D ASL) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI), in regards to their diagnostic value of preoperative glioma grade. The parameter values obtained after correction will be correlated with the diagnostic value of 3D ASL and DSC-PWI perfusion. In the current study, 50 patients with gliomas confirmed by pathology were used, including 27 low-grade gliomas (LGGs) and 23 high-grade gliomas (HGGs). Prior to surgery all patients underwent 3 Tesla magnetic resonance imaging (MRI), 3D ASL, DSC-PWI and conventional enhanced MRI scans to obtain original 3D ASL and DSC-PWI images, and the tumor regions with the most obvious parenchyma perfusion and contralateral normal white matter were selected. In these areas, the ASL-relative cerebral blood flow (ASL-rCBF), DSC-relative cerebral blood flow (DSC-rCBF) and DSC-relative cerebral blood volume (DSC-rCBV) parameter values were then obtained after correction for individual differences. The results of the present study show that ASL-CBF, DSC-CBF, DSC-CBV values and ASL-rCBF, DSC-rCBF, DSC-rCBV values increased as the grade of the glioma being imaged increased, and there was a marked difference between the HGGs and the LGGs. ASL-rCBF was significantly positively correlated with DSC-rCBF (r=0.580, P<0.01). In addition, ASL-rCBF was significantly positively correlated with DSC-rCBV (r=0.431, P<0.01). Receiver operating characteristic (ROC) curves were applied to compare the two perfusion parameters of DSC-PWI and 3D ASL in the diagnosis of glioma grade. ASL-rCBF had the highest area value under the ROC curve (0.836). The areas under the ROC curve of DSC-rCBF and DSC-rCBV were analyzed using the Z test, but the difference was not statistically significant. When ASL-rCBF, DSC-rCBF and DSC-rCBV were cutoff at 2.24, 1.85 and 1.68, the sensitivity of HGG diagnosis was 83.2, 91.3 and 91.3%, and the specificity was 77.7, 63.9 and 66.7%, respectively.

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, P<0.05), while no significance was observed between the administration group and its control group of PC-3 tumor (P >0.05).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 .

Objective To investigate the value of integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3P-RGD2) as a radiotracer in dectecting osteolytic bone metastases. Methods This is a retrospective study involving a cohort of 69 consecutive patients including 59 with lung cancer and 10 with other cancers. Patients were required to receive whole body scan (WBS) and regional SPECT/CT imaging with 99mTc-3P-RGD2 (RGD imaging) and 99mTc-MDP (MDP imaging) as a radiotracer successively within days. Final diagnosis was based on comprehensive assessment of all available data including case history, CT, MRI, SPECT/CT, PET/CT, histopathology and 6-12 months follow-up. Visual observation and semiquantitative analysis (T/N: tracer uptake ratio of osteolytic metastases to normal bone) of 99mTc-3P-RGD2 or 99mTc-MDP imaging were performed and their detective values for osteolytic metastases were compared. Results A total of 131 osteolytic metastatic lesions were retrospectively studied. Osteolytic metastases mainly presented as “hot region”, occasionally as “cool or normal region” on RGD imaging. The detection sensitivity of RGD WBS for osteolytic metastases was significantly higher than that of 99mTc-MDP WBS (80.9% vs. 46.6%, p<0.01). The sensitivity increased to 96.2% (126/131) when combining with SPECT/CT. 99mTc-3P-RGD2 imaging also promoted the detection of unknown primary tumor, lymph node metastases and offered information for clinical staging. T/N of 99mTc-3P-RGD2 in lung adenocarcinoma osteolytic metastases showed no statistical difference compared with that in squamous-cell carcinoma (6.84±3.46 vs. 7.33±3.22, t = 0.39, p = 0.71). Whereas, it was higher in osteolytic metastases from lung cancer than that from thyroid cancer (7.05±3.01 vs. 4.11±2.67, p = 0.03). Conclusion 99mTc-3P-RGD2 peptide imaging showed great potential for detection of osteolytic bone metastasis due to high expression level of integrin αvβ3 on osteoclast and most tumor cells.

There is no standard treatment strategy for patients with advanced squamous cell lung carcinoma who experienced progression with one or more lines of chemotherapy. Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown confirming antitumor activity and manageable toxicities in gastric cancers and other solid tumor. Moreover, clinical trials of S-1 on squamous cell lung carcinoma shows curative effect and lighter adverse reactions. This prospective study tried to investigate the efficacy and safety of apatinib plus S-1 as second- or third-line treatment in patients with advanced squamous cell lung carcinoma. In this open-label single-arm study(ChiCTR-OPC-16009048), patients were treated oral apatinib, at a dose of 250-500 mg daily, and S-1, at a dose of 60mg/m2 daily D1-14, repeat every 3 weeks, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Treatment was continued until disease progression or unacceptable toxicity occurs. From August 19, 2016 to May 31, 2017, 16 patients were enrolled. In 16 patients, there were 7 patients available for efficiency evaluation and 12 patients available for safety evaluation. Computed tomography (CT) scan evaluation revealed that partial response (PR) occurred in 1 of 7 patients and other 6 showed stable disease (SD). However with 2 patients of 6 patients showed stable disease (SD), the tumor demonstrates central cavitation. Hypertension is one of the most frequent adverse reactions, which appeared in 3 of 12 patients who were getting to be normal under oral antihypertensive agent. Others like hand-foot syndrome, proteinuria, diarrhea and fatigue appeared in 1 of 12 patients respectively and could be better controlled. No treatment-related hemorrhage occurred. Apatinib plus S-1 exhibits superior activity and acceptable toxicity for evaluable patients with advanced squamous cell lung carcinoma. The research team will continue the study.

目的 探讨南京及周边地区冠心病患者CYP2C19基因多态性的相关分布,分析性别和年龄与CYP2C19基因多态性的关系.方法 选取2015年5月至2016年4月期间在南京市第一医院拟使用氯吡格雷抗血小板治疗的冠心病患者共2997例.男性1963例,女性1034例;患者平均年龄66.3±11.4岁,＜65岁患者1284例,≥65岁患者1713例.采用“等位基因特异PCR”结合荧光探针技术检测CYP2C19基因多态性,并分别统计不同性别和不同年龄与基因多态性发生频率的关系.结果 本研究共检测到CYP2C19六种基因型:CYP2C19*1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3,其基因频率分别为38.5％、41.1％、6.3％、11.1％、2.7％、0.3％,共对应三种代谢表型:快代谢型(*1/*1),占38.5％;中间代谢型(*1/*2、*1/*3),占47.4％;慢代谢型(*2/*2、*2/*3、*3/*3),占14.1％.等位基因CYP2C19*1、CYP2C19*2、CYP2C19*3的频率分别为62.2％、33.0％和4.8％.不同性别和不同年龄基因多态性差异无统计学意义.结论 南京及周边地区冠心病患者CYP2C19基因多态性分布与中国其他地区人群研究结果基本一致,与性别和年龄无相关性.