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The identification of cone photoreceptor cells is important for early diagnosing of eye diseases. We proposed automatic deep-learning cone photoreceptor cell identification on adaptive optics scanning laser ophthalmoscope images. The proposed algorithm is based on DeepLab and bias field correction. Considering manual identification as reference, our algorithm is highly effective, achieving precision, recall, and F 1 score of 96.7%, 94.6%, and 95.7%, respectively. To illustrate the performance of our algorithm, we present identification results for images with different cone photoreceptor cell distributions. The experimental results show that our algorithm can achieve accurate photoreceptor cell identification on images of human retinas, which is comparable to manual identification.

BACKGROUND Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment. CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient’s T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo. CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.

miRNA-223 has been previously reported to play an essential role in hepatic cholesterol homeostasis. However, its role in regulation of biliary cholesterol secretion and gallstone formation remains unknown. Hence, mice with conventional knockout (KO), hepatocyte-specific knockout (ΔHepa) / knockdown (KD) or gain expression of miRNA-223 were included in the study and were subjected to lithogenic diet (LD) for various weeks. The gall bladders and liver tissues were harvested for cholesterol crystal imaging, gallstone mass measurement and molecular analysis. Levels of cholesterol, bile salt, phospholipids, and triglyceride were determined in serum, liver tissues, and bile by enzyme color reactive assays. A 3' UTR reporter gene assay was used to verify the direct target genes for miRNA-223. LD-induced gallstone formation was remarkably accelerated in miRNA-223 KO, ΔHepa, and KD mice with concurrent enhancement in total cholesterol levels in liver tissues and bile. Key biliary cholesterol transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented gallstone progression with reduced targets expression. Therefore, the present study demonstrates a novel role of miRNA-223 in the gallstone formation by targeting ABCG5 and ABCG8 and elevating miRNA-223 would be a potentially novel approach to overcome the sternness of cholesterol gallstone disease.

Activation and migration of donor T cells to the host target organs are critical mechanisms in the pathogenesis of graft-versus-host disease (GVHD). The role of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 in the recruitment of T cells during immune or inflammatory response is also well known. For elucidation of the mechanism of the therapeutic effect of human bone marrow derived-mesenchymal stem cells (MSC) in GVHD, we studied the effect of these cells on migration of activated donor T cells through the CCL2-CCR2 axis in vitro. MSC were expanded from donors' bone marrow mononuclear cells. After co-culturing of IL-2-activated T cells with allogeneic MSC at different ratios, the levels of CCL2 in supernatants were measured by ELISA, and CCR2 expression in CD4+/CD8+ T cells subsets were detected by flow cytometry. The effect of MSC on the migration of activated T cells in the Transwell system was studied in the absence or presence of CCL2. Our results show that CCL2 levels in supernatants of co-cultures were significantly higher than in MSC monoculture and this increase depended on the number of MSC. MSC inhibited proliferation of T cells, but did not change the percentages of CD4+ and CD8+ T cells subsets. MSC can up-regulate the CCR2 expression in CD8+ subsets rather than in CD4+ subsets; MSC enhanced migration of IL-2-activated T cells to CCL2 by increasing the expression of CCR2. The data demonstrate that MSC can enhance chemotaxis of cytokine-activated T cells through the CCL2-CCR2 axis in vitro.

Previous research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

Acute demyelinating myelopathy after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, and the exact pathogenesis remains unclear. Here, we report the case of a 20-year-old patient with B-cell acute lymphocyte leukemia (B-ALL) who developed acute demyelinating myelopathy approximately 10 months after HSCT. Magnetic resonance imaging revealed high T2 signal intensity lesions from the C2-T4 levels of the spinal cord. Treatments with high doses of corticosteroids, immunoglobulins, and rituximab improved his neurologic symptoms, and he achieved 44 months of leukemia-free and graft-versus-host disease (GVHD)-free survival, with no recurrence of the demyelination myelopathy. An understanding of the contribution of immune reconstitution to the pathogenesis of demyelinating myelopathy after HSCT and the association of this disease with GVHD will require more clinical cases.

In this work, we developed a motion estimation and correction method which real-time obtained the direction and displacement of repetitive micro bulk motion (such as cardiac and respiratory motion) on an SS-OCT system without additional tracking hardware, and reduced the motion noise in optical coherence tomography angiography (OCTA). In the approach, the direction of repetitive micro bulk motion was considered fixed, and proportional relationships between the motion components in three directions were determined; Then we performed one-dimension cross-correlation to obtain depth displacement which was further used to obtain other two motion components, and greatly reduced the computation; The processing speed on a graphic processing unit was 478 pairs of B-Scans per second, and the measurement range was larger than the range of the angiogram-based methods. Lastly, corrupt angiograms were recovered by adaptive scan protocol, and reduced acquisition time in comparison with the previous work. This article is protected by copyright. All rights reserved.

Identification of cone photoreceptor cells (CPCs) is essential for the diagnosis and treatment of various retinal disorders. In the present work, a new automated unsupervised learning-based method is proposed for the identification of CPCs in adaptive optics scanning laser ophthalmoscope images. This method consists of the following steps: image denoising, CPC number estimation, bias field correction, unsupervised CPC identification, and merging close CPC identification data. By comparing our results with those obtained manually, it was found that the proposed method showed high effectiveness, with the precision, recall and F1 score values of 92.9%, 84.4% and 88.4%, respectively. Furthermore, healthy retinal AO-SLO images with the difference in CPC densities and pathological (diabetic retinopathy) AO-SLO images are processed by our method. The results demonstrated that our method exhibited a good accuracy for the identification of CPCs in diabetic retinopathy and healthy retinas.

Backgroud: Pressure injuries (PIs) bring a considerable physical and mental burden on immobile patients, and have put families and government under tremendous pressure to cover the cost of treatment. Therefore, this protocol proposes to identify risk factors of developing PIs in immobile patients from systematic reviews (SRs) and clinical practice guidelines (CPGs), in order to establish a risk prediction model for developing PIs and identify individual risk factors that can be modified to aid prevention. Methods: Electronic databases and specific databases for CPGs and SRs will be searched. Study selection and data collection will be performed independently by two reviewers. All included SRs and CPGs will be subject to critical appraisal. RevMan 5.3 will be used to calculate the pooled odds ratio (ORP) after appraising the quality of eligible studies, and the risk predictive model will be established using logistic regression model. A narrative synthesis, evidence summary table, and Sankey diagram will also be performed. Results: The results of this study will be submitted to a peer-reviewed journal for publication. Conclusion: This systematic review will provide a risk prediction model of PI developing. INSPLAY registration number: INPLASY2020100097

BackgroudMiRNA-223 has previously been reported to play an essential role in hepatic cholesterol homeostasis by suppressing cholesterol synthesis, attenuating cholesterol uptake by hepatocyte from and promoting cholesterol efflux into the blood. However, its role in regulation of biliary cholesterol secretion and gallstone formation remains unknown.MethodsMice with conventional knockout (KO), hepatocyte-specific knockout (ΔHepa) / knockdown (KD) or gain expression of miRNA-223 were included in the study and were subjected to lithogenic diet (LD) for various weeks. The gallbladders were harvested and subjected to cholesterol crystal imaging and gallstone mass measurement. Liver tissues were collected for western blotting, RT-qPCR, and immunohistochemistry staining. Levels of cholesterol, bile salt, phospholipids, and triglyceride were determined in serum, liver tissues, and bile by enzyme color reactive assays. 3’ UTR reporter gene assays were used to verify the direct target genes for miRNA-223.ResultsLD-induced gallstone formation was remarkably accelerated in miRNA-223 KO, ΔHepa, and KD mice with concurrent enhancement in total cholesterol levels in liver tissue and bile. Key biliary cholesterol transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented gallstone progression with reduced targets protein expression.ConclusionThe present study demonstrates a novel role of miRNA-223 in the regulation of hepatic bile cholesterol secretion pathway and gallstone formation by targeting ABCG5 and ABCG8 expression. Therefore, elevating miRNA-223 would be a potentially novel approach to overcome the sternness of cholesterol gallstone disease.Graphical Abstract

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN.

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases.

Cone photoreceptor cell identification is important for the early diagnosis of retinopathy. In this study, an object detection algorithm is used for cone cell identification in confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images. An effectiveness evaluation of identification using the proposed method reveals precision, recall, and [Formula: see text]-score of 95.8%, 96.5%, and 96.1%, respectively, considering manual identification as the ground truth. Various object detection and identification results from images with different cone photoreceptor cell distributions further demonstrate the performance of the proposed method. Overall, the proposed method can accurately identify cone photoreceptor cells on confocal adaptive optics scanning laser ophthalmoscope images, being comparable to manual identification.

Cone cell identification is essential for diagnosing and studying eye diseases. In this paper, we propose an automated cone cell identification method that involves TV-L1 optical flow estimation and K-means clustering. The proposed algorithm consists of the following steps: image denoising based on TV-L1 optical flow registration, bias field correction, cone cell identification based on K-means clustering, duplicate identification removal, identification based on threshold segmentation, and merging of closed identified cone cells. Compared with manually labelled ground-truth images, the proposed method shows high effectiveness with precision, recall, and F1 scores of 93.10%, 94.97%, and 94.03%, respectively. The method performance is further evaluated on adaptive optics scanning laser ophthalmoscope images obtained from a healthy subject with low cone cell density and subjects with either diabetic retinopathy or acute zonal occult outer retinopathy. The evaluation results demonstrate that the proposed method can accurately identify cone cells in subjects with healthy retinas and retinal diseases.

Aims Podocyte apoptosis plays an important role in the pathogenesis of diabetic nephropathy (DN). Astragaloside IV (AS-IV) has been shown to protect against podocyte apoptosis. Here we aim to investigate the mechanism responsible for the protective effects of AS-IV. Main methods Diabetic db/db mice and high glucose (HG)-cultured podocytes were treated with AS-IV. Renal function and histopathological changes were measured to evaluate the therapeutic effects of AS-IV against DN. Adenovirus-mediated Klotho overexpression, Klotho siRNA, and PPARγ inhibitor were applied in vitro to investigate the potential mechanism. The expression levels of mRNA and proteins were analyzed by qRT-PCR, western blot or immunofluorescence. Intracellular ROS and mitochondrial superoxide were detected by DHE and MitoSOx Red, respectively. Cell apoptosis was evaluated by TUNEL staining and flow cytometry. Key findings AS-IV improved renal function and ameliorated podocyte injury in db/db mice accompanied with enhanced Klotho expression in glomerular podocytes. In vitro, AS-IV inhibited HG-induced podocyte apoptosis and restored HG-inhibited Klotho expression, whereas Klotho knockdown abrogated the anti-apoptosis action of AS-IV. Further study showed that adenovirus-mediated Klotho overexpression enhanced Forkhead transcription factor O1 (FoxO1)-dependent antioxidant activity and attenuated HG-evoked oxidative stress and apoptosis. AS-IV prevented HG-induced FoxO1 inhibition and oxidative stress, whereas Klotho knockdown reversed these effects. Cotreatment with PPARγ inhibitor T0070907 abolished AS-IV-induced Klotho expression and anti-apoptosis action. Significance These data suggested that AS-IV attenuated podocyte apoptosis presumably by inhibiting oxidative stress via activating PPARγ-Klotho-FoxO1 signaling pathway, thereby ameliorating DN. This study provided new insights into the molecular mechanisms of AS-IV against DN.

Background: Pressure injuries, also known as pressure ulcers, are local skin injuries. Once a pressure injury occurs, clinical treatment is relatively difficult, the treatment cycle is long, and the treatment cost is high, which brings heavy burdens to patients and society. Therefore, look for a reliable pressure injuries treatment method is 1 of the focus of clinical nursing workers. Objective: At present, there are many kinds of dressings to treat pressure injuries, and there is no uniform conclusion about which dressing is the most effective. Therefore, we systematically evaluate the effects of different dressings on the treatment of pressure injuries. Methods: We systematically searched the Chinese and English databases: PubMed, Embase, CENTRAL, CINAHL, Web of Science, CNKI, CBM, VIP, Wan Fang. Literature screening, data extraction, and quality evaluation were carried out by 2 researchers, and finally, use R software to carry out network meta-analysis. Results: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. Ethics and dissemination: Ethical approval is not applicable, since this is an overview based on published articles. Protocol registration number: INPLASY2020100087.

Background: The arrival of transcatheter mitral valve therapies has provided feasible and safe alternatives to medical and surgical treatments for mitral regurgitation. The aim of this study is to estimate the relative efficacy and safety of different transcatheter mitral valve therapies for mitral regurgitation patients through network meta-analysis. Methods: A systematic search will be performed using PubMed, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure to include random controlled trials and nonrandom controlled trials comparing the efficacy and safety of different transcatheter mitral valve techniques. The risk of bias for the included nonrandom controlled studies will be evaluated according to Risk of Bias in Non-randomized Studies - of Interventions. For random controlled trials, we will use Cochrane Handbook version 5.1.0 as the risk of bias tool. A Bayesian network meta-analysis will be conducted using R-4.0.3 software. Grading of recommendations assessment, development, and evaluation will be used to assess the quality of evidence. Results: The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: This study will provide broad evidence of efficacy and safety of different transcatheter mitral valve therapies for treatment of mitral regurgitation and provide suggestions for clinical practice and future research. Protocol registration number: INPLASY2020110034.

Background: Cancer patients are in a state of systemic immunosuppression and are considered a highly vulnerable population in the Corona Virus Disease 2019 (COVID-19) epidemic. However, the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aims to evaluate whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: We will perform comprehensive searches in PubMed, EMBASE.com, Web of Science, and the Cochrane Central Register of Controlled Trials to identify studies providing prevalence of cancer between patients with severe and non-severe illness or between non-survivors and survivors. We will use the Newcastle-Ottawa quality assessment scale to assess the quality of included studies. We will conduct pairwise meta-analyses to compute the odds ratio and 95% confidence interval using the Mantel Haenszel method with the random-effects model. The statistical heterogeneity will be assessed using the I2 statistic. Subgroup analyses, sensitivity analyses, and meta-regression analyses will be performed to explore the sources of heterogeneity. Results: The results of this study will be published in a peer-reviewed journal. Conclusion: Our meta-analysis will systematically evaluate the association between cancer and the severity and mortality of patients with COVID-19. This study will provide evidence to help determine whether cancer patients should be provided with special precautions and advised to use stronger personal protection. INPLASY registration number: INPLASY202090093.

An automated superpixels identification/mosaicking method is presented for the analysis of cone photoreceptor cells with the use of adaptive optics scanning laser ophthalmoscope (AO-SLO) images. This is an image oversegmentation method used for the identification and mosaicking of cone photoreceptor cells in AO-SLO images. It includes image denoising, estimation of the cone photoreceptor cell number, superpixels segmentation, merging of superpixels, and final identification and mosaicking processing steps. The effectiveness of the presented method was confirmed based on its comparison with a manual method in terms of precision, recall, and F1-score of 77.3%, 95.2%, and 85.3%, respectively.

Background Adults with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis, especially in patients who relapsed within 6 months of complete remission 1 (CR1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice. However, this can only be considered after complete remission 2 (CR2) is achieved. Therefore, bridging treatment is urgently needed. Case presentation In the present study, we report a relapsed adult B-cell ALL case that achieved CR2 after treatment with CD19-directed chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy. After subsequent allo-HSCT, the patient acquired 21 months of disease-free survival. Conclusion The present results confirm that both CAR-T and allo-HSCT are effective for treating refractory or relapsed B-ALL. However, a novel sequential treatment strategy with these two therapeutic methods may achieve longer disease-free survival time.

The present case report describes a rare case of T cell acute lymphoblastic lymphoma (T-LBL) in the lymph node with myeloid sarcoma in the pericardium. A 33-year-old Chinese male was admitted to hospital on 4 July 2015 exhibiting a fever and having experienced wheezing and fatigue for the previous 7 days. Routine pathological, computed tomographic, cytological and immunophenotypic observations revealed a diagnosis of T-LBL in the lymph node on 7 August 2015, without evidence of bone marrow (BM) involvement. The patient received induction chemotherapy for T-LBL and achieved partial remission. The patient was identified to have multiple serous effusion and analysis of pericardial effusion cells revealed the diagnosis of T-LBL with extramedullary myeloid sarcoma (without BM involvement) on 25 November 2015. On 30 December 2015, the patient was identified to exhibit proliferation of primary myeloid cells in the peripheral blood and BM, and an abnormal karyotype in BM cells, indicating that the complicated myeloid sarcoma involved the BM. No matched donor was available so the patient received chemotherapy to manage the disease. The patient was discharged on 31 January 2016 and ceased treatment. The patient succumbed on 19 February 2016 at home. To the best of our knowledge, T-LBL complicated with myeloid sarcoma had not been previously reported in Chinese adult male patients. In addition, the involvement of the BM and aberrant karyotype of the complicated myeloid sarcoma in the patient were rare.

The potential developmental toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years. In this study, two typical environmental oestrogen, namely, bisphenol A (BPA) and genistein (GEN) were investigated for potential embryotoxicity using the embryonic stem cell test model. Afterwards, a 4×4 full factorial design and the estimated marginal means plot were performed to assess the combined effects of these two compounds. According to the linear discriminant functions and classification criteria, bisphenol A and genistein were classified as weakly embryotoxic and strongly embryotoxic respectively. As for combined effects, the overall interaction between BPA and GEN on embryonic stem cells (ESCs) differentiation was synergistic at low dosages, however, on ESCs and 3T3 cell proliferation, the predominate action was additive. Considering the actual daily intake of these chemicals, it is concluded that BPA alone might not have adverse reproductive or developmental effects on human being. However, given that BPA and GEN do have synergistic effect at low concentration, they may disturb normal embryo development together, which could result in birth defect and behavioral alterations later in life.

The potential teratogenic effects and fetal toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years, and they have yet to be fully characterized. In the present study, the teratogenic effects of bisphenol A (BPA) and genistein (GEN) on rat embryos during their critical period of organogenesis were investigated using a whole-embryo culture experiment. The combined exposure effects of BPA and GEN were explored using a 4 x 4 full factorial design. Both BPA and GEN produced concentration-dependent inhibition of embryonic development, beginning at 32.0 and 10.0 microg/ml, respectively. Full factorial and isobologram analyses revealed a significant synergistic interaction between BPA and GEN for most end points (12 out of 20 tested), as indicated by the enhanced developmental toxicity of BPA after coexposure with different dose levels of GEN. In particular, serious malformations and a higher abnormal frequency of the central nervous system were induced by the combination of BPA and GEN. Our findings suggest that GEN may be embryotoxic and teratogenic to humans. BPA alone may not be a potential teratogen, but these two estrogenic chemicals have a synergistic effect on embryonic development when present together during the critical period of major organ formation. The current findings suggest that pregnant women should not take soy supplements, but more studies are necessary to provide a conclusive recommendation.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Vascular endothelial growth factor (VEGF) plays an important role in the initiation and regulation of angiogenesis in various tumor tissues. Recently, several therapeutic approaches based on the inhibition of VEGF function during angiogenesis. However, VEGF function in cervical cancer may not be limited to angiogenesis, and VEGF signaling may be important for the ability of these tumor cells to evade apoptosis and progress towards invasive and metastatic diseases. In our study, VEGF expression was knocked down using plasmid-based RNA interference (RNAi) and detected in cervical carcinoma cells using real-time RT-PCR to screen the best RNA interference plasmid and reveal the VEGF expression level by radiation. Cell apoptosis and tumor xenografts in nude mice were measured by flow cytometry and immunohistochemistry, respectively, to further verify the possibility of enhancing apoptosis and radiosensitivity of cervical carcinoma cells by inhibition of VEGF expression. VEGF expression was significantly inhibited and the apoptosis was efficiently increased by RNAi. Moreover, the expression of VEGF was increased in HeLa cells in vivo and in vitro only by radiation. Increased apoptotic cell death and knockdown of VEGF expression in HeLa cells indicated increased cellular sensitivity to radiation. The data suggested that inhibited VEGF expression enhances radiosensitivity in cervical cancer therapy.

High-speed multi-frame camera by which a lot of time series images with adequate spatial information can be obtained is widely used for recording in the process of wasting test. The non-kinematics supporting structure of the cemented cubic prism for three-frame in High-speed multi-frame camera is designed. The deformation of cubic prism with edge-length up to 112mm induced by gravity is calculated and the effect of the deformation on three-frame camera system is discussed. The deformation of the supporting structure of the cubic prism for three-frame under the gravity of cubic prisms and the lower-order modes are also calculated. The first natural frequency of the supporting structure of the cubic prism is better than 1000Hz, which indicates that the supporting structure of the cubic prism is with good stiffness and reliable. The research in this paper is favorable for the application of cubic beam splitter prism in high-speed multi-frame camera.

Bisphenol A (BPA), widely used in industry and dentistry, and genistein (GEN), the predominant component of soy product, are both known environmental estrogen. In the present study, we investigated the developmental toxicity of BPA and GEN and their combined effect using micromass test, which is one of three standard alternative developmental toxicity tests recommended by European Center for the Validation of Alternative Methods (ECVAM). The results showed that IC50-P (cell proliferation) and IC50-D (cell differentiation) of BPA and GEN were approximately 20 and 5 μg/ml, respectively. No observed adverse effect level (NOAEL) of BPA and GEN were 10 and 0.94 μg/ml, respectively. The manifestation of BPA as a teratogen was insufficient, although the "low dose" effect should be paid attention to. While the evidence of GEN as a teratogen was solid, especially with the consideration of "high dose" application in clinical treatment. The combined effect of BPA and GEN was generally additive action except that in MB proliferation.