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In medical fields it is very difficult and time-consuming to label samples. Only a small number of labeled samples or unlabeled samples are often encountered in medical fields. How to deal with this problem in medical diagnosis? Domain adaptation is an effective machine learning method to solve the scarce or no labeled samples problem. In this paper, an improved adversarial domain adaptation network is presented to solve this problem in tumor image diagnosis. We construct the tumor image diagnosis adversarial domain adaptation network framework. The framework consists of three parts: a feature extractor, a domain discriminator and a label predictor. The loss function of framework is designed in the paper. We design a feature extractor to acquire the domain invariant feature between the source domain and target domain. The feature extractor is an improved neural network consisting of several convolutional layers and sampling layers. The feature extractor pre-processes the input samples and gets the initial feature of the input space. The domain discriminator predicts the domain label and works adversarial with the feature extractor. The adversarial learning between the feature extractor and the domain discriminator acts as a regularization in the framework. The adversarial game can minimize the distance between the two domains and make sure the feature extractor learns the domain invariant feature. A label predictor is designed to classify the tumor image of the target domain based on the domain-invariant feature. The experiments on tumor image dataset are presented to validate the performance of proposed method. The experimental results show that the proposed method is superior to the other domain adaptation methods.

According to the ‘farming/dispersal’ hypothesis, the Early and Mid-Holocene spread of Neolithic material culture in East Asia would have arisen from dispersals of established farming populations. The authors test this hypothesis by considering the Beixin Culture that appeared in the south-west Haidai region of northern China c. 5000 BC, before spreading north and east to the coast over the subsequent millennium. While this culture had architecture, elaborate pottery and other forms of Neolithic material culture, analysis of archaeobotanical evidence from Guanqiaocunnan (4340–3970 BC) suggests an economic base of hunting, gathering and cultivating, rather than a reliance on farming.

Background Circulating genetically abnormal cells (CACs) with specific chromosome variations have been confirmed to be present in non‐small cell lung cancer (NSCLC). However, the diagnostic performance of CAC detection remains unclear. This study aimed to evaluate the potential clinical application of the CAC test for the early diagnosis of NSCLC. Methods In this prospective study, a total of 339 participants (261 lung cancer patients and 78 healthy volunteers) were enrolled. An antigen‐independent fluorescence in situ hybridization was used to enumerate the number of CACs in peripheral blood. Results Patients with early‐stage NSCLC were found to have a significantly higher number of CACs than those of healthy participants (1.34 vs. 0.19; P, Workflow of circulating genetically abnormal cells enumeration. Circulating genetically abnormal cell detection in early stage non‐small‐cell lung cancer was feasible. Circulating genetically abnormal cell test has good stability and adaptability for different patient populations. Circulating genetically abnormal cells could be used as a promising noninvasive biomarker for the early diagnosis of NSCLC.

BACKGROUND: Circulating tumor cells (CTCs) acting as “liquid biopsy” of cancer are cells that have been shed from the primary tumor, which cause the development of a secondary tumor in a distant organ site, leading to cancer metastasis. Recent research suggests that CTCs with abnormalities in gene copy numbers in mononuclear cell-enriched peripheral blood samples, namely circulating genetically abnormal cells (CACs), could be used as a non-invasive decision tool to detect patients with benign pulmonary nodules. Such cells are identified by counting the fluorescence signals of fluorescence in situ hybridization (FISH). However, owing to the rarity of CACs in the blood, identification of CACs using this technique is time-consuming and is a drawback of this method. METHODS: This study has proposed an efficient and automatic FISH-based CACs identification approach which is based on a combination of the high accuracy of You Only Look Once (YOLO)-V4 and the lightweight and rapidness of MobileNet-V3. The backbone of YOLO-V4 was replaced with MobileNet-V3 to improve the detection efficiency and prevent overfitting, and the architecture of YOLO-V4 was optimized by utilizing a new feature map with a larger scale to enable the enhanced detection ability for small targets. RESULTS: We trained and tested the proposed model using a dataset containing more than 7,000 cells based on five-fold cross-validation. All the images in the dataset were 2,448×2,048 (pixels) in size. The number of cells in each image was >70. The accuracy of four-color fluorescence signals detection for our proposed model were all approximately 98%, and the mean average precision (mAP) were close to 100%. The final outcome of the developed method was the type of cells, i.e., normal cells, CACs, gaining cells or deletion cells. The method had a CACs identification accuracy of 93.86% (similar to an expert pathologist), and a detection speed that was about 500 times greater than that of a pathologist. CONCLUSIONS: The developed method could greatly increase the review accuracy, enhance the efficiency of reviewers, and reduce the review turnaround time during CACs identification.

Background: Many studies have reported that the effects of danhong injection on idiopathic pulmonary fibrosis. However, its effects are still not well understood. The aim of this study is to assess the effects of danhong injection in the management of idiopathic pulmonary fibrosis. Methods: Electronic databases such as PubMed, MEDLINE, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database will be searched without limitations of language and geographical location. Two researchers will independently conduct research selection, data extraction, and research quality assessment. The RevMan 5.3 software and Stata 14.0 software are used for statistical analysis. Results: This study will provide high-quality comprehensive evidence for the effectiveness and safety of danhong injection in the treatment of idiopathic pulmonary fibrosis. Conclusions: The results obtained from this study will define the basis for the effectiveness and safety of danhong injection in the treatment of idiopathic pulmonary fibrosis.

3056 Background: Non-small-cell carcinoma (NCSLC) is the most common type of early lung cancer. Early detection of NSCLC is still a diagnostic challenge. Current clinical management of patients with pulmonary nodule is inefficient and may lead to misclassification, thus increasing healthcare expenses. Further, a few previous studies showed liquid biopsy and artificial intelligence (AI) platform on computed tomography (CT) imaging contributes to early NSCLC detection. Still, there is something lacking in a precise and authorized lung nodule classifier to minimize discomfort of patients. This study aims to evaluate the possibility and effectiveness of combining circulating genetically abnormal cells (CACs) with an AI platform on CT imaging to improve the diagnostic route for NSCLC. Methods: A prospective cohort of 101 in-patients was enrolled from Sep. 1, 2020 to Jan. 15, 2021, with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by CT. The participants' pulmonary nodules will be assessed by two evaluation tools: CAC detection on full blood and AI platform on CT imaging. The diagnostic performances of the two tools were evaluated in a blinded validation study respectively and combined in an open-label retrospective analysis. Results: 68 of enrolled patients were confirmed as NSCLC by pathology. The diagnostic performance of CACs for NSCLC detection was 80.9% for sensitivity and 87.3% for positive predictive value (PPV) while overall accuracy reaches 79.2%. AI platform showed a slight disadvantage as 78.6% for PPV and 73.5% for accuracy. 9 false-negative patients on CAC results could be reversed with a combination of AI platform on CT imaging, while sensitivity rises to 94.1%. However, of 33 benign nodules patients, 8 wrong diagnoses by CAC detection could decrease to 2 when combined with the results from the AI platform, which may avoid unnecessary biopsies. Conclusions: Coupling CAC with an AI platform on CT imaging could be a useful strategy to improve the diagnostic route for NSCLC and avoid unnecessary biopsies.[Table: see text]

A highly sensitive flow injection analysis (FIA)-based thermal enzyme-linked immunoassay, TELISA, was developed for the rapid detection of atrazine (ATZ) in tap water. ATZ and β-lactamase-labeled ATZ were employed in a competitive immunoassay using a monoclonal antibody (mAb). After the off-column liquid-phase competition, the mAb was captured on the Protein G Sepharose™ 4 Fast Flow (PGSFF) column support material. Injected β-lactamase substrate ampicillin was degraded by the column-bound ATZ-β-lactamase, generating a detectable heat signal. Several assay parameters were optimized, including substrate concentration, flow rates and regeneration conditions, as well as the mAb and ATZ-β dilution ratios and concentrations. The assay linear range was 0.73-4.83 ng mL(-1) with a detection limit of 0.66 ng mL(-1). An entire heat signal requires 10 min for generation, and the cycle time is less than 40 min. The results were reproducible and stable. ATZ-spiked tap water samples exhibited a recovery rate of 103%-116%, which correlated with the UHPLC-MS/MS measurements. We attributed this significant increase in sensitivity over our previously published work to the following factors: (i) the capture of already-formed immune complexes on the column via immobilized Protein G, which eliminated chemical immobilization of the antibody; (ii) off-column preincubation allows the formation of immune complexes under nearly ideal conditions; and (iii) multiple buffers can be used to, in one case, enhance immune-complex formation and in the other to maximize enzymatic activity. Furthermore, the scheme creates a universal assay platform in which sensing is performed in the off-column incubation and detection after capture in the enzyme thermistor (ET) detector, which opens up the possibility of detecting any antigen for which antibodies were available.

Listeria monocytogenes ( LM ) is a gram-positive food-borne pathogen, which can cause serious disease. Rapid screening plays an important role in the prevention and identification of LM to cause food poisoning. In this study, we describe a novel electrochemical immunosensor by self-assembled monolayers (SAM)-modified gold (Au) electrodes for the detection of LM . Mouse monoclonal antibody of LM was immobilized on the SAM through a stable acyl amino ester intermediate generated by the co-addition of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N -hydroxysuccinimide (NHS). Then, a direct sandwich format was developed, in which a polyclonal antibody for LM was conjugated to horseradish peroxidase (HRP) as the enzyme label. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were employed to characterize the stepwise assembly of the immunosensor. In the presence of H 2 O 2 , HRP catalyzes the oxidation of thionine, whose back electrochemical reduction was detected on an Au electrode at −0.3 V for 200 s with chronoamperometry measurements versus an Ag/AgCl reference electrode. The reaction conditions were optimized, such as antibody concentration, immune reaction time, activation time, and blocking time. Under optimized conditions, when the concentration of LM is ranging from 10 2 to 10 6 CFU/ml, the response current which is obtained from the labeled HRP to thionine–H 2 O 2 system and the amount of LM are linearly related ( R 2 = 0.9883). There was no need for sample pretreatment when applied to detect LM in milk. Compared with plate count assay, it was found that the relative error of two methods was lower than 8%. The sensor is a straightforward and reliable method for analysis of LM with a simple operation, sensitivity at a low cost.

Mycotoxins are highly toxic contaminants in foodstuffs and feedstuffs. The study presents a novel suspension array technology for quantifying four mycotoxins, namely, aflatoxin B1, deoxynivalenol, T-2 toxin, and zearalenone, in corn and peanut. Using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, the complete antigens of the mycotoxins became attached to the microspheres with viable activity. The optimal concentrations of each antibody and biotin-rabbit anti-goat IgG were obtained through chessboard titration. The four mycotoxins were detected simultaneously and quantitatively in corn and peanut using indirect competitive immunoassay. Multi-channel standard curves with appropriate logistic correlation (R(2)>0.9819) were respectively plotted. The broad working ranges with three to four orders of magnitude were calculated, and limits of detection at the pg level were found to be better than those obtained using high-performance liquid chromatography. The recovery rates in the actual samples generally ranged from 80.16% to 117.65%, with an intra-assay coefficient of variation lower than 15%, which indicated high accuracy and repeatability. A suspension array method for the simultaneous detection of the four mycotoxins within 4h was successfully developed using minimal samples; the method was proven to have high throughput, flexibility, accuracy and reproducibility. The approach could detect multiple contaminants in actual samples.

Developing reagents with high affinity and specificity are critical to detect the environmental hormones or toxicants. Ribosome display technology has been widely used in functional protein or peptide screening and in directed evolution of protein molecules in vitro. In this study, single-chain variable fragments (scFvs) against bisphenol A (BPA) were selected from a library constructed from splenocytes of non-immunized mice. After five rounds of selection, the selected scFvs bound to BPA with high affinity. Indirect competitive enzyme-linked immunosorbent assay (ELISA) was introduced to screen the antibody affinity and specificity to BPA. The equilibrium dissociation constants (KDS) of one clone was 1.76μM as determined by surface plasmon resonance (SPR). This study indicated that ribosome display can isolate binders to small molecules from a non-immunized naive library without any in vivo steps and can generate recombinant antibodies efficiently and rapidly. In addition, this study provides a methodological framework for detection of small molecules using recombinant antibodies.

A new anticalin against estradiol (E(2)), a kind of endocrine disruptor, was obtained in the present study to detect E(2) levels. A member of the lipocalin family from Pieris brassicae called bilin-binding protein (BBP) was employed for the preparation of a random library to specifically complex E(2). Sixteen amino acid residues at the center of the binding site, which were formed by four loops on top of an eight-stranded β-barrel, were subjected to targeted random mutagenesis. Estradiol-binding BBP variants so-called 'anticalins', which exhibit binding activity for compounds, such as E(2), were selected from the resulting library by combining both ribosome display and screening techniques. Four variants of complex E(2) with high affinity were identified. These variants exhibited dissociation constants (KDs) as low as 54.265 nM. ELISA showed that ribosome displayed anticalin (E(2)-A) specifically bound E(2). The 50% inhibition concentration (IC(50)) for E(2) was 50 ng mL(-1) and the limit of detection (LOD:IC(10)) was 0.071 ng mL(-1). The experimental results suggest that E(2)-A can be used as a potential anticalin to detect E(2) in animals.

Single chain variable fragments (scFvs) against diethylstilbestrol (DES) were selected from the splenocytes of non-immunized mice by ribosome display technology. A naive library was constructed and engineered to allow in vitro transcription and translation using an E. coli lysate system. Alternating selection in solution and immobilization in microtiter wells was used to pan mRNA-ribosome-antibody (ARM) complexes. After seven rounds of ribosome display, the expression vector pTIG-TRX containing the selected specific scFv DNAs were transformed into Escherichia coli BL21 (DE3) for expression. Twenty-six positive clones were screened and five clones had high antibody affinity and specificity to DES as evidenced by indirect competitive ELISA. Sequence analysis showed that these five DES-specific scFvs had different amino acid sequences, but the CDRs were highly similar. Surface plasmon resonance (SPR) analysis was used to determine binding kinetics of one clone (30-1). The measured K(D) was 3.79 µM. These results indicate that ribosome display technology can be used to efficiently isolate hapten-specific antibody (Ab) fragments from a naive library; this study provides a methodological framework for the development of novel immunoassays for multiple environmental pollutants with low molecular weight detection using recombinant antibodies.

The use of visible light in combination with a photosensitizing dye for the treatment of various types of tumors has been repeatedly attempted since the early 1900s when topically applied eosin and sunlight were shown to induce the regression of skin tumors1. This approach appears to be particularly attractive since i) several photosensitizers with a polycyclic chemical structure, including xanthenes2, acridines3, and psoralens4, display a preferential affinity for neoplastic as compared with normal cells; and ii) most cell constituents, in particular proteins and nucleic acids, are insensitive to the direct action of visible light. In principle, these two properties should allow one to restrict the photodynamic effects causing cell inactivation and necrosis to the dye-loaded tissue, with no concomitant damage to normal dye-free tissues, provided a suitable set of light wavelengths is selected for irradiation. Thus, photodynamic therapy exhibits a potential advantage with respect to other therapeutic modalities for tumors which are based on the use of ionizing radiations; in the latter cases, the simultaneous irreversible damage of normal tissues often limits the extent and efficacy of the treatment. Toward this aim, an ideal photosensitizer should have the following properties: i) lack of systemic toxicity; ii) selective uptake and retention by malignant tissues; iii) selective absorption of the incident light; and iv) efficient generation of photoreactive species leading to destruction of malignant tissues.

This article reports on results of treatment of 114 cancer patients at the Cancer Institute, Chinese Academy of Medical Sciences, between September 1981 and December 1984. In September 1981, a study group of clinicians, physicians and basic scientists was set up at the Cancer Institute for the study of photodynamic therapy (PDT) with HPD. During the following 39 months, 114 patients were treated by PDT alone, 8 by PDT + hyperthermia and 3 by PDT + radiotherapy. The analysis in this presentation is based on PDT alone, since the numbers of patients in the other groups is insufficient for statistical analysis.

Photodynamic therapy (PDT) of cancer using hematoporphyrin derivative (HpD) and visible light irradiation has been applied in clinical practice for several years and data on photobiology and photomedicine have been accumulated (1–3). Even so, much remains to be learned about the destructive mechanism of PDT. In order to better understand whether PDT may cause damaging effects to normal tissue in vivo, and the possible mechanism of its action, we have made a light and electron microscopic study on the effects of photodynamic treatment to normal mouse ears. In this paper we describe the results of our light microscopic observation and make a brief discussion on the significance of our findings.