SignificanceTo ensure precise tumor localization and subsequent pathological examination, a metal marker clip (MC) is placed within the tumor or lymph node prior to neoadjuvant chemotherapy for breast cancer. However, as tumors decrease in size following treatment, detecting the MC using ultrasound imaging becomes challenging in some patients. Consequently, a mammogram is often required to pinpoint the MC, resulting in additional radiation exposure, time expenditure, and increased costs. Dual-modality imaging, combining photoacoustic (PA) and ultrasound (US), offers a promising solution to this issue.AimOur objective is to localize the MC without radiation exposure using PA/US dual-modality imaging.ApproachA PA/US dual-modality imaging system was developed. Utilizing this system, both phantom and clinical experiments were conducted to demonstrate that PA/US dual-modality imaging can effectively localize the MC.ResultsThe PA/US dual-modality imaging can identify and localize the MC. In clinical trials encompassing four patients and five MCs, the recognition rate was ∼80%. Three experiments to verify the accuracy of marker position recognition were successful.ConclusionsWe effectively localized the MC in real time using PA/US dual-modality imaging. Unlike other techniques, the new method enables surgeons to pinpoint nodules both preoperatively and intraoperatively. In addition, it boasts non-radioactivity and is comparatively cost-effective.

Background: Breast cancer in China is usually identified at a later-stage compared to developed countries, and efforts have been made to improve early detection over the past years. This cross-sectional study aimed to determine the current situation of breast cancer detection and screening in a cohort of Chinese breast cancer patients. Methods: Three hundred and ten consecutive female breast cancer patients newly diagnosed and treated in Beijing Tsinghua Changgung Hospital between 2015 and 2021 were recruited. Clinicopathological data were retrieved from the patient's medical records and every individual completed surveys assessing demographics, mode of detection, screening behavior and barriers to screening. Results: Among the 310 patients, 72.6% had self-detected diseases (mostly through identification of a breast lump), 24.5% were ultrasound screening-detected, 0.3% were mammographic screening-detected and others were identified through clinical breast examination (CBE) (1.0%) or chest computed tomography (CT)/magnetic resonance imaging (MRI) (1.6%). Detection by screening was associated with earlier stages of breast cancer compared to self-detection, yet, 32.2% of self-detected diseases were at stage 0-I. A total of 166 (53.5%) patients had a screening history, with ultrasonography being mostly used and provided by employers. Leading self-perceived barrier to breast cancer screening was lack of awareness, followed by lack of access. And screening participation was associated with a younger age, higher education, being currently working, residence in urban area, and a high family income. Conclusions: Self-detection still remains a major way of breast cancer detection in Beijing, but it is not necessarily associated with a late-stage disease. The suboptimal screening rate with disparity in screening behavior can be mostly attributed to lack of awareness of the public and insufficient screening providers.

Assessing the metastatic status of axillary lymph nodes is a common clinical practice in the staging of early breast cancers. Yet sentinel lymph nodes (SLNs) are the regional lymph nodes believed to be the first stop along the lymphatic drainage path of the metastasizing cancer cells. Compared to axillary lymph node dissection, sentinel lymph node biopsy (SLNB) helps reduce morbidity and side effects. Current SLNB methods, however, still have suboptimum properties, such as restrictions due to nuclide accessibility and a relatively low therapeutic efficacy when only a single contrast agent is used. To overcome these limitations, researchers have been motivated to develop a non-radioactive SLN mapping method to replace or supplement radionuclide mapping. We proposed and demonstrated a clinical procedure using a dual-modality photoacoustic (PA)/ultrasound (US) imaging system to locate the SLNs to offer surgical guidance. In our work, the high contrast of PA imaging and its specificity to SLNs were based on the accumulation of carbon nanoparticles (CNPs) in the SLNs. A machine-learning model was also trained and validated to distinguish stained SLNs based on single-wavelength PA images. In the pilot study, we imaged 11 patients in vivo, and the specimens from 13 patients were studied ex vivo. PA/US imaging identified stained SLNs in vivo without a single false positive (23 SLNs), yielding 100% specificity and 52.6% sensitivity based on the current PA imaging system. Our machine-learning model can automatically detect SLNs in real time. In the new procedure, single-wavelength PA/US imaging uses CNPs as the contrast agent. The new system can, with that contrast agent, noninvasively image SLNs with high specificity in real time based on the unique features of the SLNs in the PA images. Ultimately, we aim to use our systems and approach to substitute or supplement nuclide tracers for a non-radioactive, less invasive SLN mapping method in SLNB for the axillary staging of breast cancer.

Photoacoustic imaging (PAI, also called optoacoustic imaging) combines light excitation and ultrasound detection for deep-tissue imaging with light absorption contrast. PAI can map the distribution of endogenous chromophores such as oxy-hemoglobin, deoxy-hemoglobin, lipids, water, and melanin. PAI performs especially well for structural and functional imaging of blood vessels. Its centimeter-deep imaging depth and ultrasound-defined resolution make it well suited for clinical application, where systems employing a linear array ultrasound probe are most commonly used due to simplicity, flexibility, and easy integration with standard ultrasonic imaging. The existing linear array based imaging systems typically employ optical fiber bundles for light delivery, such a scheme enjoys mechanical flexibility, optical stability, and simple light coupling. However, major drawbacks associated with fiber illumination include suboptimal transmission efficiency and a lack of control of the illumination pattern. Articulated arms provide an alternative light delivery option which potentially offer high transmission efficiency, stable and flexible operation, and low cost. Despite its wide applications in cosmetology, articulated arms for light delivery were understudied in the PAI community. In this paper, we reported the fabrication and experimental evaluation of an articulated arm specifically designed for linear-array-based PAI. Without losing the flexibility provided by the linear probe. Moreover, the articulated arm can be equipped with spatial positioning devices to perform three-dimensional reconstructions.

Recurrent ovarian cancer is commonly associated with lymphatic metastasis, however, supraclavicular lymph node is a rare site for metastasis. Few studies have investigated whether local debulking surgery would benefit patients with supraclavicular lymph node metastasis. We report two such cases, review the literature and discuss the potential for local debulking surgical treatment for this rare scenario. Both cases were diagnosed with recurrent ovarian cancer, with the first having left supraclavicular lymph node metastasis, while the second had right supraclavicular lymph node metastasis. Cervical lymphadenectomy was performed to relieve local symptoms in both cases followed by chemotherapy. The first case died of hepatic hilar metastasis 6 months after the surgery while the second case has to date (January 2020) survived without any recurrence 12 months postoperatively. A comprehensive search in the PubMed, Embase, and Cochrane databases was performed. According to the limited study and our cases, we conclude the lymphanectomy appears to provide potential benefit to patients with oligometastasis like right supraclavicular lymph node metastasis.

Photoacoustic imaging (PAI) is a biomedical imaging modality that can provide structural, functional, and molecular information. In PAI, laser pulses illuminate the tissue, and transient light absorption leads to instant thermal expansion and succeeding ultrasound emission. Since oxy- and deoxyhemoglobin are the major light-absorbing chromophores in biological tissue, PAI has very high contrast and is intrinsically suitable for the imaging of blood vessels. Meanwhile, superb microvascular imaging (SMI) is an emerging ultrasound imaging technique for angiography. In comparison to traditional color Doppler and power Doppler techniques which rely on the suppression of low-velocity components, SMI works by an intelligent algorithm that renders small vessels with low flow velocity visible. To date, there is no work to compare PAI and SMI in terms of vascular imaging capabilities. In this paper, we provide our recent evaluation results in imaging depths, speeds, sensitivities, and resolutions of these two modalities through phantom experiments and in-vivo studies. We used PAI and SMI to image the human forearm, and our preliminary data show that PAI is superior in imaging speeds, and sensitivities for superficial blood vessels. We acknowledge that more work needs to be done to compare the two techniques in diverse clinical applications more quantitatively, and we hope our work can pave the way for such systematic studies.

Thyroid cancer is a frequently diagnosed malignancy and the incidence has been increased rapidly in recent years. Despite the favorable prognosis of most thyroid cancer patients, advanced patients with metastasis and recurrence still have poor prognosis. Therefore, the molecular mechanisms of progression and targeted biomarkers were investigated for developing effective targets for treating thyroid cancer. Eight chip datasets from the gene expression omnibus database were selected and the inSilicoDb and inSilicoMerging R/Bioconductor packages were used to integrate and normalize them across platforms. After merging the eight gene expression omnibus datasets, we obtained one dataset that contained the expression profiles of 319 samples (188 tumor samples plus 131 normal thyroid tissue samples). After screening, we identified 594 significantly differentially expressed genes (277 up-regulated genes plus 317 down-regulated genes) between the tumor and normal tissue samples. The differentially expressed genes exhibited enrichment in multiple signaling pathways, such as p53 signaling. By building a protein-protein interaction network and module analysis, we confirmed seven hub genes, and they were all differentially expressed at all the clinical stages of thyroid cancer. A diagnostic seven-gene signature was established using a logistic regression model with the area under the receiver operating characteristic curve (AUC) of 0.967. Seven robust candidate biomarkers predictive of thyroid cancer were identified, and the obtained seven-gene signature may serve as a useful marker for thyroid cancer diagnosis and prognosis.

Objective:To investigate the effect of actin related protein 2/3 complex subunit 2 (ARPC2) gene silencing on the biological characteristics of papillary thyroid carcinoma (PTC) TPC-1 cells through lentivirus-mediated RNA interference.Methods:TPC-1 cells infected with nonsense short hairpin RNA (shRNA) sequence lentivirus (shCtrl) was used as the control group. TPC-1 cells infected with ARPC2 shRNA interference sequence lentivirus (shARPC2) was used as the experimental group, in which the expression of ARPC2 gene was specifically interfered. The effects of silencing the expression of ARPC2 gene on the proliferation of TPC-1 cells were detected by using methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, Western blot and colony formation test. Flow cytometry and Western blot were conducted to detect the effect of silencing ARPC2 gene on TPC-1 cells apoptosis and related proteins.Results:shARPC2 could efficiently infect TPC-1 cells, and the expression efficiency of green fluorescent protein was over 85%. Compared with the control group, TPC-1 proliferation was inhibited in the experimental group. The ratio of S-phase cells in the experimental group was reduced compared with that in the control group [(14.79±0.21)% vs. (21.13±0.33)%, t = 27.77, P < 0.05]. The ratio of G 1 and G 2/M-phase cells in the experimental group was increased compared with that in the control group [G 1 phase: (67.57±0.08)% vs. (62.06±0.36)%, t=25.56, P < 0.05; G 2/M phase: (17.64±0.12)% vs. (16.91±0.17)%, t=6.154, P < 0.05]. Meanwhile, the expressions of cell cycle-related proteins CDK2, CyclinE and CyclinD were reduced in the experimental group. The number of clone formation in the experimental group was less than that in the control group, the difference was statistically significant [(10±2) vs. (161±6), t=9.011, P < 0.05]. In addition, the apoptotic ratio of cells in the experimental group was higher than that in the control group [(8.60±0.77)% vs. (4.08±0.40)%, t=9.011, P < 0.05]. Western blot showed that the expressions of anti-apoptotic factors p21 and bcl-2 were reduced in the experimental group, while the expression of pro-apoptotic factor bax was increased. Conclusion:The interference with the expression of ARPC2 regulated by shRNA can inhibit the proliferation, and promote the apoptosis of PTC TPC-1 cells, indicating that ARPC2 may be a possible biological new target for the treatment of PTC.

目的 分析中、低危分化型甲状腺癌行甲状腺全切除术后接受放射性碘(131I)治疗对短期临床转归的影响.方法 选取2015年1月至2018年12月在清华大学附属北京清华长庚医院/清华大学临床医学院行甲状腺全切除术且术后静态评估为中、低危的分化型甲状腺癌患者92例,按术后是否接受放射性131I治疗分为接受131I治疗组和未接受131I治疗组,其中接受131I治疗组29例,未接受131I治疗组63例.动态随访至少2次,包括术后早期(基线)随访1次,临近研究截止时(2019年2月)再随访1次.根据2次随访时的血清甲状腺球蛋白水平及影像学等资料进行治疗效果评价和动态复发风险评估.结果 中位随访时间为12(2～48)个月.基线随访时接受131I治疗组病情较重,两组间静态复发风险、肿瘤大小及淋巴结转移数有显著差异(P<0.05).经过治疗后,近期随访时的接受和未接受131I治疗组完全缓解率分别为69.0％(20/29)、76.2％(48/63),组间差异无显著性(P=0.463).近期随访时的动态复发风险分层评估显示,两组的良好反应率、不确定反应率、生化不完全反应率和结构不完全反应率差异无显著性(P=0.160).基线状态下未达到良好反应的患者接受131I治疗后,其动态复发风险评估获得的改善较未接受131I治疗者明显提升(P=0.004).在接受131I治疗组内,与治疗前相比,131I治疗后完全缓解率显著升高(P=0.004),动态风险分层显著降低(P=0.015),血清甲状腺球蛋白水平显著降低(P=0.001).92例患者在甲状腺全切除术后,基线状态下即达到完全缓解的比例为56.5％(52/92),且肿瘤较小或转移淋巴结数目较少的亚组完全缓解率较高.结论 甲状腺全切除术后静态评估为中、低危的分化型甲状腺癌患者中,符合131I治疗适应证者虽然其基线状态下病情较重,但接受131I治疗后其短期临床转归与未接受131I治疗的患者趋于一致.肿瘤大小及转移淋巴结数目是影响甲状腺全切除手术疗效的因素.

目的 分析影响乳腺内病灶Marker放置和取出的影像学因素.方法 选择我科2018年1月-2019年2月收治的乳腺癌行新辅助治疗且乳腺病灶内放置标记夹并最终接受手术治疗的患者,根据其影像学资料及标记夹放置和取出的手术记录,比较单独及联合应用超声、X线摄影及磁共振对标记夹的放置、识别和取出的成功率的影响.结果 共11例患者入组,新辅助治疗开始前乳腺内病灶在超声、X线和磁共振检查上的检出率分别为100.0％(11/11)、72.7％(8/11)和100.0％(11/11),组间无统计学差异(P>0.05);治疗过程中,超声、X线和磁共振至少有1次识别出标记夹的检出率为0.0％(0/11)、100.0％(11/11)和45.5％(5/11),各组间均有统计学差异(P<0.05);1例在术中仅凭超声检出标记夹并导丝定位(仅凭超声定位成功率9.1％);5例拟行保乳手术者在通过X线立体定位植入导丝(X线定位成功率为100.0％);所有标本离体后X线下证实标记夹包含在标本内.结论 乳腺癌新辅助治疗乳腺病灶内标记夹放置选用超声引导下穿刺成功率高,时机在第2周期治疗开始前为宜,治疗后肿瘤接近或达到临床完全缓解且拟行保乳手术者,可优先选用X线引导定位标记夹.