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Abstract Aim The aim of this study was to investigate the lived experience of people with diabetic retinopathy and to understand the impact of the disease on them including the practical problems faced in the day‐to‐day life. Design Descriptive qualitative research. Methods A convenience sample of 11 patients with diabetic retinopathy who were hospitalized in a tertiary hospitals in Shandong province of China were enrolled. Data were collected using semi‐structured in‐depth interviews. The six‐stage thematic analysis of Braun and Clarke was used for data analysis. Results Three themes and 12 sub‐themes were extracted, namely: countdown to darkness (lack of disease knowledge, bystander's perspective, distrust of grassroots hospitals); Endless abyss (action restrictions, social isolation, stigma, lost of meaning in life, catastrophizing explanations, a heavy burden); Light chaser (craving for light, turning points in behaviour, self‐adjustment).

Objective To investigate the effects of miR-760 on the proliferation, invasion and migration of esophageal squamous cell carcinoma (ESCC) cells through targeted regulation of basic leucine zipper ATF-like transcription factor 3 (BATF3). Methods The cancer tissues and adjacent tissues of ESCC patients were collected, and normal human esophageal squamous epithelial cells Het-1A and human ESCC cell lines EC9706, KYSE150, ECA109, TE-10 were cultured in vitro. RT-qPCR was used to detect the expression of miR-760 and BATF3 mRNA. miR-760-mimics were transfected into TE-10 cells for up-regulating the expression of miR-760. CCK-8 method was used to detect cell proliferation and Transwell chamber was used to detect cell invasion as well as migration. Western blot was used to detect the expression of proliferation-related proteins cyclin D1, p21 and epithelial-mesenchymal transition related proteins MMP2, vimentin, and E-cadherin. Dual luciferase reporter gene experiment was used to confirm the targeting relationship between miR-760 and BATF3. Results Compared with the adjacent tissues and Het-1A cell, the expression of miR-760 was significantly reduced in ESCC tissues and in cell lines, while the expression of BATF3 increased (P＜0.05). The TE-10 cells with the highest expression of miR-760 were selected for subsequent experiments. Over-expression of miR-760 reduced the activity of TE-10 cells and the counting numbers of invasion and migration cells(P＜0.05). The expression of cyclin D1 and vimentin proteins increased the expression of p21 and E-cadherin proteins (P＜0.05). The results showed that miR-760 negatively regulated the expression of BATF3 (P＜0.05). Up-regulation of BATF3 expression reversed the inhibitory effects by over-expression of miR-760 on the proliferation, invasion and migration of TE-10 cells(P＜0.05). Conclusions Over-expression of miR-760 may inhibit the proliferation, invasion and migration of ESCC cells, which may be related to the targeted inhibition of BATF3 expression.

Objective: This study aimed to explore health care team members’ understanding of the factors influencing the optimal selection of central venous access devices (CVADs). Methods: The data of the study was collected using semi-structured interviews. Twenty-six hospital medical staff (four hospital manager, 15 head nurses, 7 nurse) with experience in peripheral or central catheterization from four regions (Northern China, Southern China, Northwest China, and Qinghai-Tibet China) in China were interviewed between June and October 2021. Content analysis was used to analyze the data. Results: The results revealed five themes and 14 sub-themes. Patients: concerns, resources, requirements, and evaluation (security concerns, support resources, life requirements, evaluation among patients); nurses: awareness, knowledge, and popularizing methods (awareness of intravenous therapy, understanding of professional knowledge, forms of popularizing methods); doctors: support and involvement (support for decision-making, involvement in intravenous work); hospital managers: authority, quality control and continuing education (management of catheterization authority, quality control of intravenous infusion, investment in continuing education) and environment: differences and commonalities (differences in social support, and current commonalities). Conclusion: Nurses and other healthcare team members’ understanding, selection, use, and recommendation of CVADs have an indirect effect on patients’ decision-making. Therefore, hospital managers and government departments can indirectly strengthen medical team cooperation and improve learning education in order to improve the safety of patients receiving intravenous infusions.

The distribution of cracks strongly affects the hydro-mechanical behavior and strength of soil. In order to characterize the distribution of cracks in undisturbed expansive soil, X-ray computed tomography (X-ray CT) tests were carried out for one type of undisturbed expansive soil from Mile City, China. Seven undisturbed specimens retrieved from depths between 1 and 4.7 m were used to study the evolution of cracks along the drying path. The characteristics of the cracks were quantitatively studied by 3D parameters extracted from CT images by commercial software. The test results suggested that, with an increase in suction, the total volume of the cracks gradually increased, and one large crack formed due to the merging of sub-cracks before the shrinkage limit. When the suction was larger than the suction corresponding to the shrinkage limit, degradation of the cracks caused by the collapse of the soil structure was observed. Meanwhile, due to the development of sub-cracks, the crack anisotropy caused by the typically oriented primary cracks decreased along the drying path. Finally, a conceptual model of crack development for undisturbed Mile clay was proposed based on the evolution of crack volume, number, shape, and orientation.

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

IntroductionBariatric surgery is one of the most effective methods for treating obesity. It can effectively reduce body weight and reduce the incidence of obesity-related breast cancer. However, there are different conclusions about how bariatric surgery changes breast density. The purpose of this study was to clarify the changes in breast density from before to after bariatric surgery.MethodsThe relevant literature was searched through PubMed and Embase to screen for studies. Meta-analysis was used to clarify the changes in breast density from before to after bariatric surgery.ResultsA total of seven studies were included in this systematic review and meta-analysis, including a total of 535 people. The average body mass index decreased from 45.3 kg/m2 before surgery to 34.4 kg/m2 after surgery. By the Breast Imaging Reporting and Data System score, the proportion of grade A breast density from before to after bariatric surgery decreased by 3.83% (183 vs. 176), grade B (248 vs. 263) increased by 6.05%, grade C (94 vs. 89) decreased by 5.32%, and grade D (1 vs. 4) increased by 300%. There was no significant change in breast density from before to after bariatric surgery (OR=1.27, 95% confidence interval (CI) [0.74, 2.20], P=0.38). By the Volpara density grade score, postoperative volumetric breast density increased (standardized mean difference = -0.68, 95% CI [-1.08, -0.27], P = 0.001).DiscussionsBreast density increased significantly after bariatric surgery, but this depended on the method of detecting breast density. Further randomized controlled studies are needed to validate our conclusions.

IntroductionNowadays, it has been recognized that gut microbiome can indirectly modulate cancer susceptibility or progression. However, whether intratumor microbes are parasitic, symbiotic, or merely bystanders in breast cancer is not fully understood. Microbial metabolite plays a pivotal role in the interaction of host and microbe via regulating mitochondrial and other metabolic pathways. And the relationship between tumor-resident microbiota and cancer metabolism remains an open question.Methods1085 breast cancer patients with normalized intratumor microbial abundance data and 32 single-cell RNA sequencing samples were retrieved from public datasets. We used the gene set variation analysis to evaluate the various metabolic activities of breast cancer samples. Furthermore, we applied Scissor method to identify microbe-associated cell subpopulations from single-cell data. Then, we conducted comprehensive bioinformatic analyses to explore the association between host and microbe in breast cancer.ResultsHere, we found that the metabolic status of breast cancer cells was highly plastic, and some microbial genera were significantly correlated with cancer metabolic activity. We identified two distinct clusters based on microbial abundance and tumor metabolism data. And dysregulation of the metabolic pathway was observed among different cell types. Metabolism-related microbial scores were calculated to predict overall survival in patients with breast cancer. Furthermore, the microbial abundance of the specific genus was associated with gene mutation due to possible microbe-mediated mutagenesis. The infiltrating immune cell compositions, including regulatory T cells and activated NK cells, were significantly associated with the metabolism-related intratumor microbes, as indicated in the Mantel test analysis. Moreover, the mammary metabolism-related microbes were related to T cell exclusion and response to immunotherapy.ConclusionsOverall, the exploratory study shed light on the potential role of the metabolism-related microbiome in breast cancer patients. And the novel treatment will be realized by further investigating the metabolic disturbance in host and intratumor microbial cells.

BackgroundCyclin-dependent kinases (CDKs) 4/6 inhibitors are a type of cell cycle regulation that prevents cell proliferation by blocking retinoblastoma protein (Rb) phosphorylation in the G1 to S phase transition. CDK 4/6 inhibitors are currently used mainly in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer in combination with endocrine therapy. However, primary or acquired resistance to drugs severely affect drug efficacy. Our study aims at summarizing and visualizing the current research direction and development trend of CDK4/6 inhibitor resistance to provide clinicians and research power with a summary of the past and ideas for the future.MethodsThe Web of Science Core Collection and PubMed was searched for all included articles on CDK4/6 inhibitor resistance for bibliometric statistics and graph plotting. The metrological software and graphing tools used were R language version 4.2.0, Bibliometrix 4.0.0, Vosviewer 1.6.18, GraphPad Prism 9, and Microsoft Excel 2019.ResultsA total of 1278 English-language articles related to CDK4/6 inhibitor resistance were included in the Web of Science core dataset from 1996-2022, with an annual growth rate of14.56%. In PubMed, a total of 1123 articles were counted in the statistics, with an annual growth rate of 17.41% Cancer Research is the most included journal (102/1278, 7.98%) with an impact factor of 13.312 and is the Q1 of the Oncology category of the Journal Citation Reports. Professor Malorni Luca from Italy is probably the most contributing author in the current field (Publications 21/1278, 1.64%), while Prof. Turner Nicholas C from the USA is perhaps the most authoritative new author in the field of CDK4/6 inhibitor resistance (Total Citations2584, M-index 1.429). The main research efforts in this field are currently focused on Palbociclib and Abemaciclib. Studies on drug resistance mechanisms or post-drug resistance therapies focus on MEK inhibitors and related pathways, PI3K-AKT-MTOR pathways or inhibitors, EGFR-related pathways, EGFR inhibitors, TKI inhibitors, MAPK pathways and inhibitors, and so on.ConclusionThis study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and mining research neglect directions.

Aim: Our aim in this study was to isolate potentially novel strains of fowl adenovirus serotype-4 (FAdV-4) that is currently circulating in broiler chicken flocks in Guangdong Province, China, and to compare nucleotide and amino acid (AA) sequences of their respective hexon genes. Materials and Methods: The experiment was carried out on poultry farms experiencing outbreaks of FAdV-4-associated hydropericardium syndrome (HPS). Tissue samples from the hearts and livers of deceased chickens were screened for FAdV-4 infection using hexon gene-specific polymerase chain reaction (PCR). Results: New virus isolates were used to infect 7-day-old chicks, which went onto reproduce typical HPS signs. The hypervariable region of the FAdV-4 hexon gene was PCR-amplified and sequenced. The hexon nucleotide and deduced AA sequence identities were 99.8-99.9% and 99.5-99.8%, respectively, among the four novel isolates. In addition, the new isolates were 97-100% and 96.4-99.9% identical to the nucleotide and deduced AA sequences, respectively, of FAdV-4 hexon genes available in the National Center for Biotechnology Information GenBank database. Phylogenetic analyses, based on the hexon gene sequence, revealed that the new isolates, clustered with FAdV-C; the FAdV-A, FAdV-B, FAdV-D, and FAdV-E viruses, were more distantly related. Conclusion: New FAdV-4 isolates from Guangdong Province are similar to those identified in other regions of the world. This information provides critical insight into HPS epidemiology and provides a perspective for monitoring outbreaks and developing strategies for disease prevention.

Purpose: It is very essential to diagnose gastric atrophy in the area with high prevalence of gastric cancer. Operative link for gastritis assessment (OLGA) was developed to detect the severity of gastric atrophy. The aim of this study was to develop and validate nomograms for predicting OLGA any-stage and stages III–IV in the Chinese high-risk gastric cancer population.Methods: We retrospectively analyzed 7,945 participants obtained by a multicenter cross-sectional study. We randomly selected 55% individuals (4,370 participants, training cohort) to analyze and generate the prediction models and validated the models on the remaining individuals (3,575 participants, validation cohort). A multivariate logistic regression model was used to select variables in the training cohort. The corresponding nomograms were developed to predict OLGA any-stage and stages III–IV, respectively. The area under the receiver operating characteristic curves and the GiViTI calibration belts were used to estimate the discrimination and calibration of the prediction models.Results: There were 1,226 (28.05%) participants in the training sample and 970 (27.13%) in the validation sample who were diagnosed with gastric atrophy. The nomogram predicting OLGA any-stage had an area under the curve (AUC) of 0.610 for the training sample and 0.615 for the validation sample, with favorable calibrations in the overall population. Similarly, the nomogram predicting OLGA stages III–IV had an AUC of 0.702 and 0.714 for the training and validation samples, respectively, with favorable calibrations in the overall population.Conclusions: The prediction model can early identify the occurrence of gastric atrophy and the severity stage of gastric atrophy to some extent.

Pathogenic germline mutations occurring in the BRCA1 (MIM:113705 ) and BRCA2 (MIM: 600185) , which always result in truncated protein or nonsense-mediated mRNA decay, have been identified to increase the risk of hereditary breast, ovarian, pancreatic, prostate, and melanoma cancers. Recent studies show that BRCA1/2 germline mutations also contribute to half of all hereditary breast and ovarian cancer (HBOC). In this case series, we reported a novel frameshift mutation of the BRCA1 gene. This novel frameshift mutation occurs in exon10 of BRCA1 and may result in a lack of the serine cluster domain and BRCA1 C-terminus domain, which mediates the function of BRCA1 in DNA repair and are responsible for activation function of BRCA1 . The mutation was present in a Chinese hereditary male/female breast and ovarian cancer family characterized by a high incidence of breast cancer and/or ovarian cancer among the relatives and by a high incidence of triple negative breast cancer (TNBC). Our findings speculate that BRCA1 E1148Rfs*7 mutation may be related to the occurrence of HBOC and even TNBC. Interestingly, three cases of TNBC with this novel BRCA1 mutation in this case series showed a good disease-free survival, one of them has a disease-free survival up to 7 years. Therefore, further study is required to confirm that whether this mutation is associated with good prognosis of HBOC.

The glycosylation of antibody-based proteins is vital in translating the right therapeutic outcomes of the patient. Despite this, significant infrastructure is required to analyse biologic glycosylation in various unit operations from biologic development, process development to QA/QC in bio-manufacturing. Simplified mass spectrometers offer ease of operation as well as the portability of method development across various operations. Furthermore, data analysis would need to have a degree of automation to relay information back to the manufacturing line. We set out to investigate the applicability of using a semiautomated data analysis workflow to investigate glycosylation in different biologic development test cases. The workflow involves data acquisition using a BioAccord LC-MS system with a data-analytical tool called GlycopeptideGraphMS along with Progenesis QI to semi-automate glycoproteomic characterisation and quantitation with a LC-MS1 dataset of a glycopeptides and peptides. Data analysis which involved identifying glycopeptides and their quantitative glycosylation was performed in 30 min with minimal user intervention. To demonstrate the effectiveness of the antibody and biologic glycopeptide assignment in various scenarios akin to biologic development activities, we demonstrate the effectiveness in the filtering of IgG1 and IgG2 subclasses from human serum IgG as well as innovator drugs trastuzumab and adalimumab and glycoforms by virtue of their glycosylation pattern. We demonstrate a high correlation between conventional released glycan analysis with fluorescent tagging and glycopeptide assignment derived from GraphMS. GraphMS workflow was then used to monitor the glycoform of our in-house trastuzumab biosimilar produced in fed-batch cultures. The demonstrated utility of GraphMS to semi-automate quantitation and qualitative identification of glycopeptides proves to be an easy data analysis method that can complement emerging multi-attribute monitoring (MAM) analytical toolsets in bioprocess environments.

Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these products with high yield and purity within a limited number of purification steps in a scalable fashion. A robust purification process that is able to circumvent these issues is therefore of critical importance to allow effective isolation of this group of antibodies. We investigated the addition of sodium chloride (NaCl), calcium chloride (CaCl2), and L-arginine monohydrochloride (Arg·HCl) to the elution buffer of Protein L affinity chromatography, and propose here a novel mechanism for the modification of Protein L binding avidity that can lead to enhanced high molecular weight (HMW)-monomer separation, a preferential strengthening effect of the HMW-Protein L interaction compared to the monomer-Protein L interaction. In particular, we found Arg·HCl to be the most effective salt additive in terms of purity and recovery. The mechanism we propose is different from the widely reported chaotropic effect exerted by salt additives observed in Protein A chromatography. We also demonstrate here that a final eluate containing

Abstract Background Accumulating evidence suggests that a decrease in brain-derived neurotrophic factor (BDNF) level induces a variety of psychiatric and neurological disorders. However, the expression and role of BDNF in the kidney have not been explored. The present study examined the expression of BDNF and tropomyosin-related kinase (Trk) receptors in an experimental model of chronic cyclosporine A (CsA) nephropathy. Methods Sprague-Dawley rats on a salt-deplete diet were treated daily for four weeks with vehicle or CsA. Urine profiles, apoptotic cell death, oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-OHdG), and expression of BDNF and Trk receptors (TrkB and TrkC) were compared between groups. The impact of vasopressin infusion on the urine-concentrating ability was examined by measuring the expression of aquaporin-2 (AQP-2) and BDNF and urine profiles in normal and CsA-treated rats. Results Compared with the vehicle-treated rats, rats given CsA had enhanced urine volume and declined urine osmolality. Immunohistochemistry and immunoblotting showed that BDNF and Trk receptors were constitutively expressed in kidneys from vehicle-treated rats. This was confirmed by double immunofluorescent staining for Na-K-ATPase-α1, AQP-1, and AQP-2. By contrast, the expression of these factors decreased in kidneys from CsA-treated rats (BDNF: 51.1 ± 19.5% vs. 102.0 ± 30.3%, p

Research on how risk is perceived by drivers is vital to driving behavior research and driving safety. As risk can be divided into subjective and objective risk, in this paper, we focus on modeling subjective risk perception by drivers using a deep learning method. Different drivers often perceive different levels of subjective risk under the same driving conditions. In addition, different driving conditions or driving events will have different effects on drivers. Based on these two risk perception features, in this paper, we first design an experiment on a city road with two lanes to assess the level of subjective risk perceived by drivers belonging to different groups. We then use a deep learning network-based method to abstract features of the driving environment. These environmental features are integrated with driver risk perception data and this information is used as training and testing data for the learning network. Finally, a long-short-term memory-based method is adopted to model the subjective risk perception of individual drivers based on traffic conditions and vehicle operation data from the driver's vehicle. Our results show that the proposed method can effectively model the subjective risk perception behavior of drivers, allowing for end-to-end risk perception prediction in future driving assistance systems.

Lightweight sandwich structures with highly porous 2D cores or 3D (three-dimensional) periodic cores can effectively withstand underwater explosion load. In most of the previous studies of sandwich structure antiblast dynamics, the underwater explosion (UNDEX) bubble phase was neglected. As the UNDEX bubble load is one of the severest damage sources that may lead to structure large plastic deformation and crevasses failure, the failure mechanisms of sandwich structures might not be accurate if only shock wave is considered. In this paper, detailed 3D finite element (FE) numerical models of UNDEX bubble-LCSP (lightweight corrugated sandwich plates) interaction are developed by using MSC.Dytran. Upon the validated FE model, the bubble shape, impact pressure, and fluid field velocities for different stand-off distances are studied. Based on numerical results, the failure modes of LCSP and the whole damage process are obtained. It is demonstrated that the UNDEX bubble collapse jet local load plays a more significant role than the UNDEX shock wave load especially in near-field underwater explosion.