The management pattern of axillary lymph nodes (ALN) in early-stage breast cancer patients with sentinel lymph node (SLN) micro-metastasis (SLNMM) and the prognosis are currently unclear in China. This study aimed to analyze the choice of clinical management and prognosis of patients with early-stage breast cancer combined with SLNMM in China. This multicenter retrospective study included T1-3N0M0 female breast cancer patients who have undergone surgery and with SLNMM (including isolated tumor cells) from July 2019 to April 2023 at 5 centers in southern China. Characteristics of breast cancer, management patterns, and ALN metastasis were collected. The prognosis outcome included local recurrence (LR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). A total of 339 patients were included, with a mean age of 52.44±11.73 years. The baseline data showed a tumor length diameter of 2.20 (Interquartile range 1.60, 2.90) cm. Micrometastases were detected by intraoperative freezing in 196 (57.8%) patients, whereas 143 (42.2%) were negative intraoperatively and only detected by postoperative pathology. A total of 136 (40.1%) patients received ALN dissection (ALND) and 111 (33.1%) patients received radiotherapy. LR was observed in 4 (1.2%) patients, and DM was observed in 6 (1.8%) patients. With the median follow-up time of 26.73 (range 0.40, 57.13) months, median DFS and median OS were not reached. The 3-year DFS and 3-year OS were 97.2%, and 99.5%, respectively. This study found that there are differences in the management of ALN in SLNMM patients of China, based on various surgical procedures for breast cancer. However, the rate of LR was low, thus omitted ALND might be a feasible ALN management option.Table: 93Pn (%)N=339Clinical staging T1155 (46.1) T2170 (50.6) T311 (3.3)Molecular subtype Luminal A143 (42.4) Luminal B138 (40.1) Her-2 over-expression34 (10.1) Triple-negative22 (6.5)Number of sentinel lymph node micrometastases ITC15 (4.4) 1-2319 (94.1) ≥35 (1.5)Non-sentinel lymph node metastases20 (5.9)Patients with mastectomy295 (87.0)Underwent ALND125 (42.4)Radiotherapy only46 (15.6)Observation only124 (42.0)Patients with breast-conserving37 (10.9)Underwent ALND8 (21.6)Radiotherapy only25 (67.6)Observation only3 (10.8)Patients with breast reconstruction7 (2.1)3-years DFS (%)97.2%3-years OS (%)99.5%ITC: Isolated tumor cells; ALND: Axillary lymph node dissection; DFS: Disease-free survival; OS: Overall survival. Open table in a new tab

The High Intensity heavy-ion Accelerator Facility (HIAF) is being constructed to generate intense beams of primary and radioactive ion for a wide range of research fields. Hence, a Monolithic Active Pixel Sensor (MAPS) named Nupix-A2 has been developed in a 130-nm High Resistivity CMOS process. The Nupix-A2 can simultaneously measure the particle hit' energy, arrival time, and position. It consists of a 128 × 128 pixel array, a digital-to-analog converter array, and a digital control module. The Nupix-A2 can measure energy deposition from 300 e- to over 50 ke- and time duration from 13 μs to 140 μs. This sensor also offers full readout mode and fast readout mode. In full-readout mode, all pixels measure arrival time and energy, suitable for real-time beam monitoring and image reconstruction. In fast-readout mode, only particle hit's positions are detected and read out. This paper presents the design of the Nupix-A2.

Various interventions were used to control the COVID-19 pandemic and protect population health, including vaccination, medication and nonpharmaceutical interventions (NPIs). This study aims to examine the cost-effectiveness of different combinations of NPIs (including social distancing, mask wearing, tracing-testing-isolation, mass testing, and lockdown), oral medicine (Paxlovid), and vaccination (including two-dose and three-dose vaccination) under the Delta and Omicron pandemic in China. We constructed a Markov model using a SIRI structure with a one-week cycle length over one-year time horizon to estimate the cost-effectiveness of different combinations in China from societal perspective. Effectiveness of interventions, disease transition probabilities and costs were from published data, quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios (ICER) and net monetary benefits were calculated for one-year time horizon. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. Scenario analysis was developed to examine different situations under the Omicron pandemic. Under the Delta pandemic, implementing the combination of social distancing, mask wearing, mass testing and three-dose vaccination was the optimal strategy, with cost at $11165635.33 and utility of 94309.94 QALYs, and had 60% probability of being cost-effective compared with other strategies. Three-dose vaccination combinations were better than two-dose combinations. Under the Omicron pandemic, antigen testing was better than nucleic testing by avoiding cross infections; second, adding Paxlovid or lockdown to the combined intervention strategies could increase limited health outcomes at huge cost and thus were not cost-effective; last, encouraging patients to stay at home can save societal costs compared with concentrated quarantine at hospitals. Three-dose vaccination and self-quarantine of asymptomatic and mild cases can save total costs. Under the Omicron pandemic outbreak, antigen testing is a better way to control the pandemic, and adding Paxlovid or lockdown to intervention combinations is not cost-effective.

Ischemic stroke is a brain disease with high incidence. To reduce disability rate of patients, accurate diagnosis of ischemic stroke is required. Electrical impedance tomography (EIT) is a non-invasive imaging method. With this method, conductivity distribution which reflects pathological variation of brain can be reconstructed. However, reconstruction of conductivity distribution is an ill-conditioned inverse problem which leads to poor reconstructed images and affects accuracy of diagnosis. In this paper, a novel method based on DenseNet is proposed for the diagnosis of ischemic stroke. Unlike the traditional image-based detection method, ischemic stroke is be diagnosed by directly processing measured voltage data which avoids the ill-posed reconstruction process. In order to verify the performance of the proposed DenseNet method, the effects of noise, inclusions with different shapes, change of head shape and contact impedance variation are quantitatively analyzed and evaluated. In addition, the performance of the proposed method is tested by animal experimental data. The results show that the proposed method shows better performance than the diagnosis methods based on fully connected and shallow convolution neural networks. Detection of ischemic stroke based on the proposed method is implemented by directly processing boundary measurement. This avoids solving inverse problem which is required in the image-based detection method. Ischemic stroke can be more accurately diagnosed by the proposed method.

The Monolithic Active Pixel Sensor (MAPS) is a good candidate for the inner tracking system of the Electron–Ion Collider in China (EicC). Hence, a MAPS with a pixel pitch of ∼30 µm is being designed. Two 130 nm CMOS processes have been proposed as candidates for this MAPS design. The first one is a commercial standard twin-well low-resistivity (<50 Ω cm −3 ) process, and the other one is a quadruple-well high-resistivity (>1 kΩ cm −3 ) process. A 3-dimensional TCAD model of the pixels has been established to evaluate the Minimum Ionizing Particles (MIPs) induced charge collection in these two processes. This paper will discuss the study of charge collection efficiency, charge collection time, and charge sharing among pixels.

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

OBJECTIVE:To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS).METHODS:Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting.RESULTS:RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).CONCLUSION:MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.

A Monolithic Active Pixel Sensor (MAPS) is currently being designed in a new 130nm high-resistivity (> 1 k Omega.cm) CMOS process for full image beam monitoring in the carbon-ion therapeutic facility. The charge sensing node collects the charge deposited by the carbon ions that pass through the MAPS. A 3-dimensional TCAD model of the pixel has been established to study the carbon-ion induced process in the MAPS. This paper will discuss the thickness of the depletion layer, the charge collection efficiency, the charge collection time, and the characteristics of NMOS devices with different bias voltages and carbon-ion hitting locations.

Purpose/Objective(s) To investigate the feasibility of removable fiducial marker implantation with the intelligent navigation bronchoscopy technology in a frameless robotic radiosurgery system tracking. Materials/Methods CT scans of an inflatable anti-corruption pig lung were acquired, and two simulated tumor lesion sites were designed in the left and right lung lobes by intelligent navigation software, respectively. According to the principle of fiducial marker implantation, 24 removable fiducial markers were implanted around each simulated tumor lesion via bronchus after intelligent guiding. Simulating the end-expiratory state, the pig lung was scanned again to obtain CT images of the implanted removable fiducial markers and the number of successfully implanted fiducial markers was recorded. Six deliverable treatment plans were designed using the planning system, and then the pig lung plans were delivered based on the simulated respiratory movements. After the treatment, the implanted removable fiducial markers were retrieved through bronchoscopy, and the number of successful retrievals was recorded. The rigid body error and translation error were extracted and analyzed from the log file. Results No removed fiducial markers slipped and fell off during the experiment. 24 removable fiducial markers were successfully implanted under bronchoscopic intelligent magnetic navigation guidance, with a 100% implantation success rate (24/24) and 100% removable success rate (24/24). The fiducial marker tracking rate was 83.33% (20/24), with 4 fiducial markers being too far away from the simulated tumor location to be used during the tracking process. The data from the log file displayed that the mean rigid body error for 6 groups was 1.45 mm, the mean translation error was 1.78 mm. Conclusion The technology of bronchoscopy intelligent navigation and implantation of removable fiducial marker is feasible, and the tracking accuracy of the frameless robotic radiosurgery system can meet the clinical requirements, which has a good clinical application and teaching application prospect.

Tumor spread through air spaces (STAS) has been identified as an invasive pattern in lung adenocarcinoma (ADC), but the correlations between clinicopathologic features and STAS and the prognostic value of STAS have not been well studied in all stages of ADC with a lager sample size. The purpose of this study was to investigate these correlations and evaluate the prognostic value of STAS in patients with ADC after radical surgery.

The verification of exposure to nerve agents is a serious challenge, especially in cases of soman (GD) poisoning. Protein adducts are reliable biomarkers, that provide forensic information and evidence during incidents of terrorism or sporadic poisoning. Mass spectrometry, coupled with a proteomics approach, was established for the forensic analysis of GD-based protein adducts. The fragmentation pathways of GD-based protein adducts were investigated for the first time using electrospray ionization tandem mass spectrometry. Three abundant natural loss product ions, [M+2H-54]2+ (loss of two carbon cations), [M+2H-72]2+ (loss of tert-butyl and methyl moieties), and [M+2H-84]2+ (loss of the pinacolyl moieties), were observed in each of the GD-labeled adducts, and the product ions were independent of protein structure and exposure route. A unique mechanism for the formation of product ions involving GD-protein adducts is proposed here. These findings support the development of a simple and precise forensic analysis technique to rapidly verify GD poisoning using these three GD-related product ions.

Objective: To evaluate the value of whole exome sequencing (WES) in prenatal clinical application. Methods: A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed. Results: Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results. Conclusions: WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

This paper describes a 5-bit cyclic column-parallel ADC for Monolithic Active Pixel Sensor. The column-parallel ADC combines the dedicated sample phase and the signal conversion phase into a single phase. Moreover, it has a high tolerance to the offset of the comparators in the ADC by generating 1.5 bit in every stage. Each column-parallel ADC covers a small area of 100 μm × 200 μm, consumes 4.5 mW at 3.3 V supply and provides the sampling rate of 10 MS/s with the dynamic range of 1000 mV. The results show that the ADC has a signal-to-noise and distortion ratio (SNDR) of 28.47 dB. Its DNL and INL are −0.039/0.055 LSB and −0.048/0.095 LSB, respectively.

The prognostic and clinical significance of single hormone receptor expression in breast cancer has not been clearly established. The goal of this study was to conduct a meta-analysis to compare the clinical outcomes of patients with ER+PR− tumours and ER−PR+ tumours to those of patients with ER+PR+ tumours. A systematic review of the literature was conducted to identify studies that compared the clinical outcome of patients with ER+PR− tumours or ER−PR+ tumours with those of patients with ER+PR+ tumours. A total of 18 studies met the inclusion criteria and included 217,485 women. Standard methods for meta-analysis were used, including fixed-effect models. Patients with ER+PR− tumours or ER−PR+ tumours had significantly worse DFS (HR 1.60, 95% CI 1.44–1.77 and HR 2.27, 95% CI 1.67–3.09), BCSS (HR 1.43, 95% CI 1.33–1.53 and HR 1.82, 95% CI 1.68–1.98) and OS (HR 1.38, 95% CI 1.28–1.47 and HR 1.48, 95% CI 1.17–1.89) than those of patients with ER+PR+ tumours. In subgroup analyses, patients who had ER+PR− tumours experienced a higher risk of recurrence than patients with ER+PR+ tumours in the HER2− (HR 1.57, 95% CI 1.32–1.87), LN − (HR 2.07, 95% CI 1.44–2.86) and endocrine therapy (HR 1.65, 95% CI 1.45–1.89) subgroup. Patients who had HER2− and ER−PR+ tumours had an increased risk of recurrence compared with patients who had HER2− and ER+PR+ tumours (HR 3.10, 95% CI 1.92–5.10). Among patients with hormone receptor-positive breast cancer, patients with either ER+PR− tumours or ER−PR+ tumours have a higher risk of recurrence and a shorter survival time than those with ER+PR+ tumours. Patients with both types of breast cancer need additional or better treatments.

OBJECTIVE Embryonic stem cells (ESCs) mainly originate from totipotent cells in early-stage of mammalian embryo and could proliferate in a manner of un-limitation. This study aimed to investigate roles of Axin2 in proliferation of ESCs and explore the associated mechanisms. MATERIALS AND METHODS Axis inhibition protein 2 (AXIN2) over-expression (LV5-AXIN2) and AXIN2 RNA interfere (LV3-AXIN2-RNAi) vectors were structured and transfected into H9 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to evaluate cell proliferative activity. Flow cytometry analysis was employed to measure apoptosis of H9 cells. AXIN2, β-catenin, transcription factor 4 (TCF4), c-myc, c-jun and Cyclin D mRNA levels and protein expressions were determined using quantitative real-time PCR (qRT-PCR) and Western blotting assay. RESULTS LV5-AXIN2 and LV3-AXIN2-RNAi were successfully structured with higher transfecting efficacy. AXIN2 gene silencing remarkably increased proliferative activity and AXIN2 treatment significantly induced apoptosis of H9 cells, comparing with blank vector group (p<0.05). AXIN2 gene silencing significantly enhanced B-cell lymphoma-2 (Bcl-2) expression and remarkably inhibited cleaved caspase-3 expression comparing to that in blank vector group (p<0.05). AXIN2-RNAi treatment significantly enhanced and AXIN2 over-expression significantly reduced β-catenin and TCF4 expression, comparing to that in blank vector group (p<0.05). AXIN2 gene silence activated down-stream molecules of Wnt/β-catenin signaling pathway, including c-jun, c-myc, and Cyclin D1 (p<0.05). CONCLUSIONS AXIN2 gene silencing reduced apoptosis by regulating mitochondria-associated apoptosis signaling pathway and enhanced proliferation by modulating molecules in Wnt/β-catenin signaling pathway. Therefore, targeting of aberrant apoptosis and AXIN2 might be a novel clinical strategy to inhibit aging and enhance self-renewal of ESCs.

This paper presents a common readout system for the development of the pixel detectors at the HIRFL. The readout system consists of the front-end cards (FEC) and the common data acquisition unit (CDAU). The FEC reads data from the customized detector boards and sends it to the CDAU through the high-speed optical fiber link. To reduce the risk of radiation-induced failures, the Flash-based Microsemi Smartfusion2 FPGA SOC has been chosen as the main FPGA on the FEC. The CDAU receives data from the FECs, processes the data and ships the data to the data computer through the PCIe interface. This paper will discuss the design, implementation and first test results of this readout system.

Beam monitoring system in heavy ion therapy facilities ensures the beam energy deposition can accurately cover the dedicated tumour region. For the purpose of building a high-precision beam monitoring system, a Monolithic Active Pixel Sensor (MAPS) is under development. The charge sensing node in the MAPS is formed by an n-well - p(-) epitaxial layer junction and it collects charge by drift and diffusion. In order to optimize the performance of the charge sensing node, the depletion region, the diode capacitance, the charge collection efficiency and the charge collection time have been studied with TCAD simulations. This paper discusses the simulation results with different bias voltage, node structures and heavy ion hitting locations.

The heavy-ion experiments at the Heavy Ion Research Facility in Lanzhou (HIRFL) and the future High-Intensity Heavy-Ion Accelerator Facility (HIAF) in China drives the development of Monolithic Active Pixel Sensor (MAPS) for particle tracking detectors. To reduce the data volume from the MAPS based detectors, a centroid finder that can calculate the geometric centroid of the region of the energy deposition quickly has been designed. The centroid calculation is realized by distance screening among the coordinates of the pixels in the fired region. Performance study with the data from heavy-ion experiments in HIRFL proves that the centroid finder can accurately find the centroids and reduce the data volume from the MAPS by approximately one order of magnitude.