The current quantitative methods of bilirubin have disadvantages such as high cost and low sensitivity. Due to the negative correlation between the level of serum bilirubin and the risk of cardiovascular diseases, a fluorescent ratiometric film sensor was developed aiming at bilirubin detection at low level concentration. Blue-emitting and red-emitting gold nanoclusters were assembled into the same film using layer-by-layer self-assembly technology. Detection of bilirubin was achieved based on the intensity ratio of the two nanoclusters. Bilirubin exposure causes fluorescent quenching of the film. The fluorescence intensity ratio of the two cluster probes had quantitative relationship versus bilirubin concentration. Based on this film sensor, a portable fluorescence detection system was designed for the ratiometric sensing of bilirubin. The hardware of the system was mainly composed of main control chip STM32F407, TSL237 and TSL238T optical frequency sensor. A light-avoiding dark room and detection light path were designed through three-dimensional printing to reduce the interference from ambient light and improve detection accuracy. Experimental results showed that the proposed detection system had strong anti-interference, good stability and accuracy. The linear coefficient of bilirubin detected by this system was 0.987. The system presented good results in reproducible experiments and possessed a good linear relationship with the data obtained by standard spectrofluorometer. The portable system is expected to detect serum bilirubin at low levels.
Bilirubin ; Fluorescence ; Fluorescent Dyes ; Gold ; Metal Nanoparticles ; Spectrometry, Fluorescence/methods*

Objective:To investigate the stiffness characteristic of triple-negative human breast cancer at different size in a implantation nude female mice model using shear wave elastography(SWE) and to compare the clinical pathologic features of tumors with elasticity variables.Methods:Human breast cancer MDA-MB-231 cells were injected into 30 nude female mice and 27 transplanted tumors were successfully found in nude female mice. Ultrasound and SWE were longitudinally performed on maximum diameter plane of 21 tumours in 21 nude mice. The elastic parameters of maximal elasticity(Emax), mean elasticity (Emean) and standard deviation of elasticity(Esd) were recorded. The mice were divided into 3 groups according to the tumor size. They were group A with tumor size less than or equal to 5 mm, group B with tumor size greater than 5 mm and less than or equal to 10 mm, group C with tumor size larger than 10 mm and smaller than or equal to 15 mm. Compared with pathology, the relationships between Ki67 of transplanted tumor and elastic parameters were analyzed.Results:As the transplanted tumors increased, the values of Emax, Esd, Ki67 all increased. The lesions maximal size, Emax, Esd, Ki67 were significant higher in group B ( P<0.001, P=0.006, P=0.002, P=0.026) and group C ( P<0.001, P<0.001, P<0.001, P=0.028) than group A. The other parameters were not significantly different among the groups(all P>0.05). The size of transplanted tumors was significantly and positively correlated with Emax ( rs=0.673, P=0.001), Esd ( rs=0.661, P=0.001), and Ki67 ( rs=0.509, P=0.018). Conclusions:SWE Emax and Esd can reflect the tumor tissue stiffness change and biological activity during the tumor growth.

Objective: To evaluate the risk factors in terms of clinical characteristics and sonographic features regarding solitairy thyroid papillary carcinoma (PTC) for the lateral cervical lymph node metastasis(LLNM) and then to establish nomogram model. Methods: All patients were confirmed to be solitary PTC in paraffin wax pathology after thyroidectomy in Fudan University Shanghai Cancer Center from January to September 2016. Meanwhile, the status of lateral cervical lymph node metastasis was determined referring to postoperative pathology. Clinical characteristics including gender, age, preoperative thyroid stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), central lymph node metastasis (CLNM) and sonographic features of the PTC lesion including maximum tumor diameter, location, aspect ratio, relation with thyroid capsule, echo, margin, acoustic halo, microcalcification were evaluated for the association with lateral cervical lymph node metastasis using univariate and multivariate logistic regression analyses. Then the nomogram model was established and its application value was evaluated using ROC. Results: Out of 1 174 patients, 125 patients (10.6%) presented lateral neck lymph node metastasis and 10 patients presented skipping metastasis.Univariate analysis showed gender, preoperative Tg and TGAb, CLNM, maximum tumor diameter, location, close to the thyroid tumor capsule, echo, aspect ratio, acoustic halo, microcalcification were associated with LLNM(P<0.05). Binomial logistic regression analysis indicated CLNM, maximum tumor diameter of larger than 10 mm, superior or multiple location, microcalcification were independent risk factors of LLNM. The AUC of the nomogram model was 0.865, the sensitivity was 88.0%, the specificity was 75.2%, and the accuracy was 76.6%. Conclusions As for patients with single focal PTC, CLNM, larger lesions, microcalcification, superior location are associated with lateral neck lymph node metastasis. The nomogram model can be tried for clinical application.

Objective To evaluate the risk factors in terms of clinical characteristics ,serological indicators and sonographic features regarding thyroid papillary carcinoma ( PTC) for the central neck lymph node metastasis . Methods One thousand one hundred and seventy‐four patients accepted thyroid cancer surgery at Fudan University Shanghai Cancer Center from January to September 2016 were enrolled . All patients were confirmed to be solitary PTC in paraffin wax pathology after thyroidectomy .M eanwhile ,the status of central neck lymph node metastasis was determined referring to postoperative pathology . All features of the PTC lesion in terms of clinical ,serological and sonographic features were evaluated for the association with central neck lymph node metastasis using univariate and multivariate logistic regression analysis . Meanwhile ,a nomogram model was established for the determined risk factors . Results Out of 1 174 patients ,469 patients ( 39 .9% ) presented central neck lymph node metastasis ,univariate analysis showed that age , gender , preoperative thyroglobulin ( Tg ) and thyroid peroxidase antibody ( T POAb ) , maximum diameter ,location ,close to the thyroid capsule ,AP/T R ,echo ,acoustic halo ,and presence of microcalcification were related with CLNM ( P ＜ 0 .05 ) . M ultivariate logistic regression analysis demonstrated that less than 55 years‐old , male , Tg higher than 20 eg/L , T POAb less than 1 kU/L , maximum diameter larger than 10 mm ,and presence of microcalcification were independent risk factors for CLNM . T he nomogram was established based on independent risk factors determined by the logistic regression with the AUC 0 .714 ,specificity 73 .1% ,and sensitivity 59 .7% . Conclusions For patients with single focal PTC lesion , younger age , male , higher Tg , lower T POAb , and larger lesions containing microcalcificatin on ultrasound are associated with central neck lymph node metastasis .

Objective To explore the ultrasound-guided diffuse optical tomography (DOT) distribution difference and clinical characteristics of T 1-T3 breast carcinoma. Methods Four hundred and forty-seven breast cancer patients with 455 breast lesions were enrolled.The lesion maximal diameter and total hemoglobin concentration(THC) were obtained by ultrasound-guided DOT before breast surgery biopsy.The patients age,body mass index(BMI),and the distances from lesion to skin and nipple were measured,lymph node status were also assessed.According to the 7th Edition of the AJCC Cancer Staging, all tumors were divided into T1( ≤ 2 cm),T2(2 cm < lesion ≤ 5 cm),and T3( > 5 cm) three groups according to maximum diameter on ultrasound.Results Out of 455 breast cancer lesions,148 lesions were stage T1,251 lesions were stage T2,56 lesions were T3.The age,lesion size,lesion THC and the distances between lesions and nipples of breast cancer patients were found that there were significant differences among T1,T2 and T3(all P = 0.000). With T stages increasing,the age of breast cancers patients decreased,the distance between lesions and nipples decreased,the THC increased.THC of breast cancer T 2 [(221.0 ± 56.0)μmol/L] and T3[(233.1 ± 54.0)μmol/L] were significant higher than that of T1 [(181.6 ± 70.4)μmol/L](all P = 0.000).There were all no significant difference for BMI and the distancefrom lesion to skin among different stages T( P > 0.05).With T stages increasing,the ratio of lymph node metastasis increased(T1 26.4%,T2 49.8%,T3 55.4%; P =0.000).Conclusions With breast cancer T stages increasing,T HC increases,the age of the patients decreases,lymph node metastasis rate increases.

Objective To investigate the clinical value of conventional ultrasonographic ( US),US-guided diffuse optical tomography ( US-guided DOT ) and both combined to assess treatment response of breast cancer to neoadjuvant chemotherapy( NAC). Methods Eighty-eight breast cancer patients,totally 93 lesions were included in the study. Pre-and post-last chemotherapy,size,and total hemoglobin concentration ( THC) of each lesion were measured by conventional US and US-guided DOT before biopsy,the change of lesion Size( ΔSize) and the change of THC( ΔTHC) were calculated respectively.Based on the guidelines to evaluate the response to treatment in solid tumors,the responses to NAC were classified into complete response, partial response, static disease, progressive disease groups. The histological response to chemotherapy were categorised as partial pathological response and complete pathological response using Miller and Payne system. Results Of 93 breast cancers,the overall response rate was 81.7%,the cPR rate was 24.7%. According to ROC curve analysis,when ΔSize 42.6% and ΔTHC 23.9% as cutoff values to evaluate the complete response and partial response,the area under the curve ( AUC ) were 0.666 and 0.751,respectively,the AUC of US and US-guided DOT combined in parallel and in series were 0.680 and 0.737 respectively.When ΔSize 64.5% and ΔTHC 27.2% as cutoff values to evaluate complete pathologial response,the AUC were 0.690 and 0.728 respectively,the AUC of US and US-guided DOT combined in parallel and in series were 0.693 and 0.726 respectively. Conclusions US-guided DOT and US can be used to predict breast cancers response to NAC,US and US-guided DOT combined in parallel and in series can not improve response prediction comparing with US or US-guided DOT alone.

Objective To retrospectively study the anisotropy of shear wave elastography (SWE)quantitative parameters of breast lesions,and the correlation with histopathology.Methods A total of 281 consecutive women with 281 breast lesions (179 malignant,102 benign) were included,who underwent conventional ultrasound (US) and 2D SWE before surgical excision.Three acquisitions each for transverse and longitudinal planes were obtained,and maximum elasticity (Emax),mean elasticity (Emean),standard deviation (Esd) of the whole lesion and ratio between the elasticity in the mass and the fatty tissue (Eratio)were recorded.Anisotropic difference (AD) and anisotropy factors (AF) were calculated,and correlation with histopathology was analyzed.Results The average Emax,Emean and Esd of transverse planes were significantly higher than those of longitudinal planes.AF showed positive correlation with quantitative elasticity (Emax,Emean,Esd and Eratio) (P =0.000),and was significantly higher in malignant lesions than that in benign besions (P =0.000).AUC of AF was significantly higher than that of AD (P ＜0.001).AF was significantly higher in invasive ductal carcinoma than that in ductal carcinoma in situ.Higher AF was associated with higher histopathological grades of invasive ductal carcinoma (P =0.000),and correlated with ER/PR(+).Conclusions Anisotropy of SWE is an indicator of malignancy of breast lesions,and is of predictive value for prognosis in breast cancer.

Objective To investigate the value of ultrasound-guided diffuse optical tomography (US-guided DOT) to predict clinical efficacy of breast cancer neoadjuvant chemotherapy (NAC).Methods Eighty-eight breast cancer patients with 93 lesions were included.Pre-and post-last chemotherapy,the size,total hemoglobin concentration (THC) of each lesion were measured by ultrasonography (US) and US-guided DOT.Based on the guidelines to evaluate the response to treatment in solid tumors,the lesions of treated breast cancer patients were divided into 4 types of responses to NAC:complete response (CR),partial response (PR),stable disease (SD),and progressive disease (PD).Efficient groups include CR and PR groups.Results As expected,no significant difference was found in size and THC for untreated lesions (all P ＞0.05).However,for the treated lesions(P =0.001),THC,pre-vs post-treatment size changes (△Size％) (P =0.002) and THC changes (△THC％) (P ＜0.001) were significantly varied among CR,PR,SD,PD groups.When compared with pre-treated,tumor sizes after treatment were changed significantly in all CR(P ＜0.001),PR(P ＜0.001),SD (P =0.023) and PD (P =0.001),while significant change of THC was only found in CR(P ＜0.001),PR(P ＜0.001) and SD (P =0.002).When △THC％ =23.9％ as the threshold for prediction of NAC efficiency,the area under the curve of ROC was 0.75,and the sensitivity was 73.7％,specificity was 76.5 ％,positive predictive value was 93.3 ％,negative predictive value was 39.4％,accuracy was 74.2％.Conclusions △size％ changes in consistent with △THC％ among the intergroups,but their changes levels are different,the highest change percent appears in CR,gradually decreased in PR,SD groups.△THC％ will contribute to predict preoperative clinical NAC efficacy.

Objective To retrospectively study the quantitative features and diagnostic value of 3-dimensional shear wave elastography (3D-SWE) in breast lesions.Methods A total of 198 consecutive women with 198 breast lesions (125 malignant,73 benign) were included,who underwent conventional ultrasound (US) and 3D-SWE before surgical excision.Quantitative parameters of transverse planes,sagittal planes and coronal planes were calculated,including maximum elasticity (Emax-w),mean elasticity (Emean-w),standard deviation (Esd) of the whole lesion and ratio between the stiffest elasticity (Emean-s)in the lesion and the fatty tissue (Eratio).Area under ROC curve(AUC) for combination of quantitative parameters and US were calculated.Results The AUC,sensitivity and specificity for US were 0.919,88.0％ and 78.1 ％,respectively.In the total 198 lesions,Emax-w,Emean-w,Esd,Eratio and Emean s were significantly lower in coronal planes than those in transverse and sagittal planes (all P ＜0.001).AUC for combination of each quantitative parameter and US were significantly higher than those of US (all P ＜0.05),except Emean-w of transverse plane,while there was no significant difference among the three orthogonal plane (P＞0.05).Sensitivity significantly increased by combining US with Emean-s,Eratio (transverse,sagittal and coronal planes),Emean-w (coronal and sagittal planes) or Esd (coronal and transverse planes) (all P＜0.05).Combination of US and Emean w of coronal plane yielded significantly higher sensitivity than those of transverse and sagittal planes.Conclusions Combination of quantitative features of 3D-SWE and US can significantly increase diagnostic accuracy and sensitivity in breast lesions.Emean-w of coronal plane yields the highest sensitivity.

Objective To investigate the relationship of greyscale ultrasonographic signs and clinical pathological characteristics with axillary lymph node metastasis in invasive breast cancer.Methods Three hundred and thirty-five patients with pathologically confirmed breast cancer were retrospectively analyzed,which categorized into 2 groups,including lymph node metastasis group and lymph node non-metastasis group.The clinical and pathological characteristics included age,primary tumor size,histological grade,and molecular subtypes.The ultrasonographic features were examined including orientation,shape,margin,echo pattern,posterior acoustic feature,and calcification.Chi-Square test and Logistic regression analysis were performed to analyze the relationship of clinical pathological characteristics and greyscale ultrasonographic signs with axillary lymph node metastasis.Results Age (＜45 years),primary tumor size (≥2 cm),histological grade(Ⅲ grade),molecular subtype (Luminal B),and number of margin angulation (＞ 10) contributed to axillary lymph node metastasis in 335 cases,according to univariate analysis (P ＜0.05).Multivariate Logistic regression analysis showed age (OR =0.573,P =0.019),the primary tumor size (OR=2.359,P =0.001),histological grade (OR=0.529,P =0.008),and number of marginangulation (OR =1.889,P =0.031) were risk factors of axillary lymph node metastasis in breast cancer.Conclusions Univariate and multivariate analyses show the correlation between ultrasonographic features and axillary lymph node involvement.Combining with clinical pathological data,it can provide a predictor of axillary lymph node metastasis.