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As a hallmark of cancer, angiogenesis plays a pivotal role in carcinogenesis. However, the correlation between angiogenesis and the evolution of BRAFV600E kinase inhibitor‒acquired resistance is still poorly understood. In this study, we reported that the molecular signatures of angiogenesis were enriched in early on-treated biopsies but not in disease-progressed biopsies. The process of drug resistance development was accompanied by the remodeling of vascular morphology, which was potentially manipulated by tumor-secreted proangiogenic factors. Further transcriptomic dissection indicated that tumor-secreted IGF1 drove the vascular remodeling by activating the IGF1/IGF1R axis on endothelial cells and sustained the prompt regrowth of resistant tumor. Blockade of IGF1R with small molecules at an early stage of response disrupted vascular reconstruction and subsequently delayed tumor relapse. Our findings not only showed the correlation between IGF1-mediated tumor vascular remodeling and the development of acquired resistance to BRAFV600E kinase inhibitor but also provided a potential therapeutic strategy for the prevention of tumor relapse in clinical application.

The buckling behaviour of cold-formed steel (CFS) Sigma sections in purlin-sheeting systems is investigated by Finite Element Analysis (FEA) in this paper. A total of 434 specimens with different web heights, thicknesses and lengths are simulated. The comparison of the longitudinal stress distributions obtained from the EN1993-1–3 and FEA is presented. The moment capacities and load–displacement curves of Sigma sections are predicted by FEA. The significant influence of the distortional-lateral torsional buckling interaction on the performance of Sigma purlins is illustrated. The modified Direct Strength Method (DSM) formulae are proposed to predict the flexural capacities of partially restrained Sigma sections under uniformly distributed uplift loading (UDUL).

The English grammar question bank can reserve a large number of special knowledge points and special categories of questions, which is helpful for English learners. Therefore, we design and verify the application effect of an intelligent question bank system. We construct an English grammar knowledge map, which is used to design the system architecture, including basic layer, data layer, service layer, business layer, and user layer. On the basis of the system structure, the index system of the item bank is established, and the functional modules of the system are designed comprehensively. Finally, we design a system database based on MySQL and give the table of knowledge points of English grammar. In order to verify the performance of the designed English grammar intelligent test bank system, a verification experiment is carried out. The experiment selects the accuracy rate of English grammatical feature extraction, recall rate, convergence, and system configuration accuracy. The experimental results show that the proposed system can extract English grammatical features with higher accuracy, and the recall rate is more satisfactory. Compared with the reference systems, the designed system configuration accuracy is higher.

Twiddler’s syndrome (TS) is a hardware-related complication of deep brain stimulation which has not been well documented and is probably underreported. The objective of this study is to comprehensively describe TS by systematically reviewing the related literature. The methods include selecting the eligible studies based on the inclusion and exclusion criteria. Data about studies and TS were collected. A descriptive statistical analysis of the extracted data was performed. We found 18 eligible studies describing 23 patients with TS. The mean age of the 23 patients was 61.4 ± 15.9 years (range, 16–79 years.). The percentage of TS in the female population was 91.3% (females: 21/23). The incidence of postoperative TS was 1.4% (6 out of 437) per patient and 1.1% (8 out of 709) per extension wire. The mean time to clinical presentation was 9.9 ± 10.3 months (range, 0.5–36 months). Nineteen of the twenty-three patients presented with a rebound of previous symptoms. Twelve of the twenty-three patients had high impedance at the postoperative checkup of the DBS system. A plain X-ray indicated twisted extension wires in almost all these patients. All patients meeting the definition of postoperative device-related TS underwent revision surgery. TS is more prevalent in females. Based on the typical clinical symptoms (rebound of the previous symptoms, high impedance, and X-ray demonstration), the differential diagnosis can often be straightforward. TS should thus be taken into consideration when attempting to explain or rule out hardware malfunction. The timely recognition and proper revision of TS can prevent further serious damage.

Automatic ultrasound image segmentation is crucial for clinical diagnosis and treatment. However, ultrasound image segmentation is challenging because of the ambiguous structure, incomplete boundary and analogous appearance among different categories. To address above challenges, we propose a flexibly plug-and-play module called vector self-attention layer (VSAL) to conduct long-range spatial and channels reasoning simultaneously. Moreover, it also preserves translational equivariance and considers multi-scale information, by using geometric priors and multi-scale calibration. Besides, a novel context aggregation loss (CAL) is designed to consider the contextual dependences between inter-classes and intra-classes based on context prior. The proposed methods, VSAL and CAL, are flexible enough to be integrated in any CNN-based methods. We validate the effectiveness of the modules on two different ultrasound datasets, multi-target Fetal Apical Four-chamber dataset and one-target Fetal Head dataset. Experiment results reveal significant performance gain when using the proposed modules.

Background As the mainstay treatment for coronary heart disease (CHD), aspirin alone is reported to be less effective than in combination when treating CHD. The aim of this analysis was to systematically evaluate the efficacy and safety of aspirin in combination with other drugs for the treatment of CHD, as well as its effect on the levels of inflammatory factors. Methods Electronic databases were searched from 2011 to 2021 and randomized controlled trials (RCTs) on aspirin in CHD patients were included in our study. Data was statistically analyzed using Stata 16.0 (StataCorp). Results A total of 13 RCTs were included, with a total of 1,442 patients. Compared with control group (aspirin alone) group, the response rate in the treatment group (aspirin in combination with other drugs) was significantly improved [odds ratio (OR) =5.11; 95% confidence interval (CI): 3.56-7.35], while the incidence of adverse reactions was markedly decreased (OR =0.36; 95% CI: 0.25-0.53). Before treatment, no significant differences were identified in the levels of inflammatory factors between the groups The inflammatory factors included C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). After treatment, CRP and TNF-α levels were significantly lower in both groups compared with those before treatment. However, there was no statistically significant difference in IL-6 levels after treatment between the groups. Discussion Aspirin is effective in the treatment of CHD, both alone and in combination. However, the latter has higher clinical efficacy and safety, and can significantly reduce the level of inflammatory factors in CHD patients.

The objective of this study was to explore a new method for the differential diagnosis between fetal double aortic arch (DAA) and right aortic arch with mirror-image branches (RAA-MB). Clinical data and prenatal echocardiographic features of the DAA (n = 22) and RAA-MB (n = 65) confirmed by postnatal or autopsy findings were analyzed retrospectively. The angles between the two aortic arches in the DAA group and between the right aortic arch and the mirror branch were measured. The differences between the two groups and differential diagnosis value of the angles were compared and analyzed based on the receiver operating characteristic curve. The proportion of left-sided ductal arteriosus (100%) was higher in the DAA group than that (32.3%) in the RAA-MB group, (P

The rise of Internet of Things (IoT) technology promotes the rapid development of location services industry. The idea of smart connectivity also provides a new direction for Location-Based Social Networks (LBSNs). However, due to limited calculate ability and internal storage space of IoT devices, historical location data of users is generally stored in the central server, which is likely to cause the disclosure of users’ private data. In this paper, we propose a Blockchain-enabled Privacy-Preserving Location Sharing (B-PPLS) scheme, which is a new framework that not only protects user location privacy but also provides effective location sharing services for users. For B-PPLS, location data owners can share the location area instead of location coordinates to Requesters, in order to realize the location privacy preserving. Also, the Merkle hash tree is utilized to divide the location area, so as to realize the multilevel privacy preserving. Furthermore, four algorithms are proposed to achieve the four stages of initialization, location record, location sharing, and location verification, respectively. Finally, we analyze the security of the proposed B-PPLS scheme and compare the performance with other related location privacy-preserving schemes by experimental evaluation.

Background and aim Westernized high-fat diet increases the risk for inflammatory bowel diseases (IBDs), yet with insufficient understanding of the role of high-protein diet. We aimed to identify the effect of high-protein diets from different dietary proteins (casein, whey protein, soy protein) on experimental colitis and its impact on microbiota, structure and function of colonic mucus layer. Methods Female BALB/c mice were fed by standard diet, high-casein diet (HCD), high whey protein diet or high soy protein diet for 4 weeks. The susceptibility of dextran sulfate sodium (DSS)-induced colitis in mice and thickness of colonic mucus layer were compared after different dietary interventions, associated with the identification of the reversal effect of broad-spectrum antibiotic intervention (0.5 g/L of vancomycin and 1 g/L of neomycin sulfate, metronidazole and ampicillin in drinking water). Further analysis was performed on the synthesis of mucin, microbiota and sialidase involved in degradation of mucus layer. Results High-protein diets aggravated acute DSS-induced colitis independent of protein composition, while broad-spectrum antibiotics reversed this effect. HCD significantly altered the composition of bacteria in the colonic mucus layer, especially Bacteroides thetaiotaomicron and total mucin-degrading bacteria; besides, it increased sialidase concentration and reduced the thickness of mucus layer. However, it exhibited no significant effect on the synthesis of Muc2. Broad-spectrum antibiotics decreased the abundance of mucin-degrading bacteria and sialidase concentration while increased the thickness of mucus layer. Conclusion High-protein diet shifts microbial composition and thickness of colonic mucus layer, leading to the aggravation of acute DSS-induced colitis.

Background Exosomes are extensively reported to be strongly associated with many immunologic diseases, including Crohn disease (CD). Meanwhile, the dysfunction of macrophage activation has been proposed to be critical for the pathogenesis of CD. However, it is an unsettled issue whether serum exosomes from CD could activate macrophages and participate in its pathogenesis. Our study intended to clarify the role of CD-derived exosomes on macrophages to elucidate a novel mechanism and possible diagnostic and therapeutic strategies. Methods Serum exosomes were isolated and identified. Functional assays in vitro were performed on Raw264.7 macrophages, followed by exosomal microRNA (miRNA) profiling and bioinformatics analyses via high-throughput sequencing. In animal experiments, exosomes were intraperitoneally injected into dextran sulfate sodium–induced colitis. Results In vitro CD-derived exosomes induced proinflammatory cytokine expression and increased macrophage counts. Meanwhile, the intervention of exosomes from CD with epithelial cells led to increased permeability of the intestinal epithelial barrier. In vivo, CD-derived exosomes could circulate into the intestinal mucosa and significantly aggravate colitis. Furthermore, CD changed the miRNA profile of exosomes and further analysis revealed a differential expression of let-7b-5p. Mechanistically, the let-7b-5p/TLR4 pathway was recognized as a potential contributor to macrophage activation and inflammatory response. Furthermore, serum exosome–mediated let-7b-5p mimic delivery alleviated colitis significantly. Conclusions Our study indicated that serum exosomes can circulate into the intestinal mucosa to aggravate colitis by regulating macrophage activation and epithelial barrier function. In addition, CD showed altered exosomal miRNA profiles. Furthermore, serum exosome–mediated let-7b-5p-mimic delivery may significantly alleviate colitis, providing potential novel insight into an exosome-based strategy for the diagnosis and treatment of CD.

Background To explore the analgesic efficacy of extracorporeal shock wave (ESW) combined with percutaneous vertebroplasty (PVP) after reduction in overextension position in the treatment of osteoporotic thoracolumbar compression fractures in postmenopausal women. Methods The data of postmenopausal women with osteoporotic thoracolumbar compression fracture admitted in our department from January 2017 to October 2019 were analyzed retrospectively. They were divided into groups of unipedicular percutaneous kyphoplasty (U-PKP n = 21), bipedicular PKP (B-PKP n = 20), and ESW combined with PVP after reduction in overextension position (EP-PVP n = 18). The improvement of pain and vertebral height in three groups was compared. Results Postoperative compression rate and Cobb angle of vertebral fractures in the three groups were all lower than those before surgery, and the differences between pre-operation and post-operation were statistically significant (P P P Conclusions In our small-sample study, all three treatment schemes can treat osteoporotic compression fracture of thoracolumbar vertebrae in postmenopausal women, relieve pain, and improve quality of life. ESW combined with PVP after reduction in overextension position could achieve a good vertebral reduction rate and improve kyphosis, and may reduce the application of analgesic drugs.

OBJECTIVE Differentiating central nervous system (CNS) lymphoma from other intracranial malignancies remains a clinical challenge in surgical neuro-oncology. Advances in clinical fluorescence imaging contrast agents and devices may mitigate this challenge. Aptamers are a class of nanomolecules engineered to bind cellular targets with antibody-like specificity in a fraction of the staining time. Here, the authors determine if immediate ex vivo fluorescence imaging with a lymphoma-specific aptamer can rapidly and specifically diagnose xenografted orthotopic human CNS lymphoma at the time of biopsy. METHODS The authors synthesized a fluorescent CNS lymphoma-specific aptamer by conjugating a lymphoma-specific aptamer with Alexa Fluor 488 (TD05-488). They modified human U251 glioma cells and Ramos lymphoma cells with a lentivirus for constitutive expression of red fluorescent protein and implanted them intracranially into athymic nude mice. Three to 4 weeks postimplantation, acute slices (biopsies, n = 28) from the xenografts were collected, placed in aptamer solution, and imaged with a Zeiss fluorescence microscope. Three aptamer staining concentrations (0.3, 1.0, and 3.0 μM) and three staining times (5, 10, and 20 minutes) followed by a 1-minute wash were tested. A file of randomly selected images was distributed to neurosurgeons and neuropathologists, and their ability to distinguish CNS lymphoma from negative controls was assessed. RESULTS The three staining times and concentrations of TD05-488 were tested to determine the diagnostic accuracy of CNS lymphoma within a frozen section time frame. An 11-minute staining protocol with 1.0-μM TD05-488 was most efficient, labeling 77% of positive control lymphoma cells and less than 1% of negative control glioma cells (p < 0.001). This protocol permitted clinicians to positively identify all positive control lymphoma images without misdiagnosing negative control images from astrocytoma and normal brain. CONCLUSIONS Ex vivo fluorescence imaging is an emerging technique for generating rapid histopathological diagnoses. Ex vivo imaging with a novel aptamer-based fluorescent nanomolecule could provide an intraoperative tumor-specific diagnosis of CNS lymphoma within 11 minutes of biopsy. Neurosurgeons and neuropathologists interpreted images generated with this molecular probe with high sensitivity and specificity. Clinical application of TD05-488 may permit specific intraoperative diagnosis of CNS lymphoma in a fraction of the time required for antibody staining.

How to measure the level of intellectual property protection has been the focus of academic and practical circles, however, rigorous empirical evidence remains scant. The influencing factors of intellectual property protection are summarized and analyzed, and the evaluation index system of intellectual property protection at the provincial level is constructed with judicial, administrative, pluralistic, and environmental protections as the first-class indicators. The feasibility and reliability of the index system are tested empirically by using the 2019 data of intellectual property protection in certain provinces and cities in China. The index system can objectively reflect the level of intellectual property protection in provincial regions. The research has certain enlightenment to strengthen the performance appraisal of intellectual property protection and improve the level of intellectual property protection in the region and even in the country.

Yue Wu,1,* Jiajun Yin,2,* Bixiu Yang,3 Li Tang,4 Wei Feng,5 Xiaowei Liu,1 Xingfu Zhao,1 Zaohuo Cheng1 1Department of Geriatric Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 2Brain Science Basic Laboratory, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 3Department of Clinical Psychology, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 4Department of General Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China; 5Department of Social Prevention and Control, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, Wuxi, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zaohuo ChengDepartment of Geriatric Psychiatry, The Affiliated Wuxi Mental Health Center with Nanjing Medical University, 156 Qianrong Road, Wuxi, 214151, Jiangsu Province, People’s Republic of ChinaTel +86 510 830 30359Fax +86 510 830 12201Email chengzaohuo@126.comBackground: Apolipoprotein (APOE) ϵ4 is recognized as an independent risk factor for mild cognitive impairment (MCI). However, not everyone with the ϵ4 allele develops MCI, suggesting that other susceptibility genes exist. This study aimed to identify MCI susceptibility genes, including BIN1, MC1R, STARD6, and PVRL2, in elderly Han Chinese and to verify their association with APOE ϵ4 allele in MCI onset.Methods: To determine whether polymorphisms in BIN1 (rs6733839, rs7561528), MC1R (rs2228479), STARD6 (rs10164112), and PVRL2 (rs6859) occurred in elderly MCI patients carrying APOE ϵ4 allele, we carried out a case–control study including 285 MCI patients and 326 healthy controls.Results: Statistically significant differences in the proportion of APOE ϵ4 carriers, and BESCI, ADAS-cog, and CNT scores existed between the NC and MCI groups (all P < 0.01). Frequencies of the rs10164112 T and rs6859 A alleles were significantly higher in the latter than in the former (P = 0.01; 0.029). However, no significant differences in allele and genotype distribution of BIN1 (rs6733839, rs7561528) and MC1R (rs2228479) existed between samples in our two groups (all P > 0.05). When stratified by APOE ϵ4 status (carriers/non-carriers), genotype frequencies of BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 among the four groups (NCϵ4+, NCϵ4-, MCIϵ4+, MCIϵ4-) were significantly different. Additionally, our results suggest a significant association between MCI and BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 (all P< 0.05) in elderly carriers.Conclusion: This suggests that among the Han Chinese, MCI in elderly APOE ϵ4 carriers may be related to the BIN1 (rs7561528), STARD6 (rs10164112) and PVRL2 (rs6859). Genotype AA of rs7561528 and TT of rs10164112 might be protective factors against MCI in elderly APOE ϵ4 carriers.Keywords: mild cognitive impairment, BIN1, MC1R, STARD6, PVRL2, APOE, polymorphism, association analysis

BACKGROUND The incidence of breast cancer among women of reproductive age is increasing, as well as the desire for children at late childbearing age. Identifying factors that may be associated with fetal malformation and maternal and fetal prognosis has gained importance. We describe a 32-year-old woman with breast cancer who gave birth to a son with congenital bilateral cryptorchidism after treatment, with a literature review performed. CASE SUMMARY A 32-year-old woman with breast cancer who had been treated by surgery and radiotherapy experienced recurrence and underwent a second surgery, adjuvant chemotherapy, and targeted therapy. Her tumor cells were negative for estrogen receptor (ER) α, progesterone receptor (PR), and p53; positive for ERβ, human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), and Ki67. She had pathogenic BRCA gene mutations. She became pregnant within 2 years and delivered a boy with congenital bilateral cryptorchidism. The boy underwent bilateral orchidopexy. As of this writing, the woman and her son are both healthy. CONCLUSION HER2 overexpression, positivity for EGFR, Ki67, and ER, and PR negativity are associated with a poor prognosis in breast cancer. While no link has been established statistically between treatment for breast cancer and cryptorchidism in a subsequent pregnancy, this case suggests the possibility that ERβ and gene mutations may be contributing factors.

Background: To investigate the changes of intestinal microbiota and metabolites in sepsis mice with acute gastrointestinal injury before and after the use of antibiotics, and to explore the possible effects of these changes on the body. Methods: Twenty-four 6-8-w-old SPF-grade C57BL/6J male mice were selected, and the mice were randomly divided into three groups. The mice were treated by tail vein injection for 3 days. The intestinal motility of mice after administration was detected. The mice feces were collected for 16S rRNA and Untargeted metabonomics detection. Results: The use of antibiotics in sepsis mice can change the composition of intestinal microbiota and metabolites. LD3, AD3 and LAD3 samples had significant differences in bacterial species. Desulfovibrio was the species with a significant difference in LAD3. In addition, we found that the composition of those intestinal microbiota were correlated with changes in intestinal motility. The untargeted metabolomics analysis showed that the fecal metabolites of LD3 and LAD3 samples were significantly different. In addition to the basic metabolites, Benzoic acid and 4-Hydroxybenzoic acid were also found, and Desulfovibrio was associated with them. Conclusions: The use of antibiotics in sepsis mice can lead to changes in the intestinal microbiota and metabolite levels, which may be related to the severity of acute gastrointestinal injury in sepsis mice. Inhibiting Desulfovibrio in the intestine and using Benzoic acid and 4-Hydroxybenzoic acid as a marker for the production of Desulfovibrio may reduce the inflammatory degree of acute gastrointestinal injury in sepsis.

Jaundice occurs as a symptom of various diseases, such as hepatitis, the liver cancer, gallbladder or pancreas. Therefore, clinical measurement with special equipment is a common method that is used to identify the total serum bilirubin level in patients. Fully automated multi-class recognition of jaundice combines two key issues: (1) the critical difficulties in multi-class recognition of jaundice approaches contrasting with the binary class and (2) the subtle difficulties in multi-class recognition of jaundice represent extensive individuals variability of high-resolution photos of subjects, huge coherency between healthy controls and occult jaundice, as well as broadly inhomogeneous color distribution. We introduce a novel approach for multi-class recognition of jaundice to detect occult jaundice, obvious jaundice and healthy controls. First, region annotation network is developed and trained to propose eye candidates. Subsequently, an efficient jaundice recognizer is proposed to learn similarities, context, localization features and globalization characteristics on photos of subjects. Finally, both networks are unified by using shared convolutional layer. Evaluation of the structured model in a comparative study resulted in a significant performance boost (categorical accuracy for mean 91.38%) over the independent human observer. Our work was exceeded against the state-of-the-art convolutional neural network (96.85% and 90.06% for training and validation subset, respectively) and showed a remarkable categorical result for mean 95.33% on testing subset. The proposed network makes a performance better than physicians. This work demonstrates the strength of our proposal to help bringing an efficient tool for multi-class recognition of jaundice into clinical practice.

With the development of industry and technology, mechanical systems’ safety has strong relations with the diagnosis of bearing faults. Accurate fault diagnosis is essential for the safe and stable operation of rotating machinery. Most former research depends too much on the fault signal specificity and learning model’s choices. To overcome the disadvantages of lacking intrinsic mode function (IMF) modal aliasing, low degree of discrimination between data of different fault types, high computational complexity. This paper proposes a method that combines multi-scale weighted entropy morphological filtering (MWEMF) signal processing and bidirectional long-short term memory neural networks (Bi-LSTM). The developed rolling bearing fault diagnosis strategy is then implemented to different databases and potential models to demonstrate the greatly improved system’s ability to reconstruct the time-to-frequency domain characteristics of fault signature signals and reduce learning cost. After verification, the classification accuracy of the proposed model reaches 99%.

Jin Zhang,1 Changsong Wang,2 Kai Kang,1 Haitao Liu,2 Xiaowei Liu,1 Xiaonan Jia,1 Kaijiang Yu1 1Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China; 2Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, People’s Republic of ChinaCorrespondence: Kaijiang YuDepartment of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang 150001, People’s Republic of ChinaTel +86-451-53643849Email Yu_kaijiang@126.comPurpose: Sepsis, a destructive inflammatory response syndrome, is the principal reason to induce death in the intensive care unit. Loganin has been proved to possess the property of anti-inflammation, antioxidant, neuroprotection, and sedation. The primary aim of this study was to evaluate whether Loganin could alleviate acute kidney injury (AKI) during sepsis and investigate the latent mechanisms.Methods: Septic AKI models were established by cecal ligation and puncture (CLP) surgery in mice and given Loganin (20, 40, 80 mg/kg) by gavage. Lipopolysaccharides (LPS)-stimulated human kidney proximal tubular (HK2) cells incubated in Loganin (5, 10, 20 μ M) were used to explore the accurate mechanisms. Survival rate, renal function (creatinine and blood urea nitrogen), and renal pathological changes were detected in septic mice. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), mitochondrial membrane potential, mitochondrial calcium overload, and nuclear factor E2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway activation in vivo and in vitro were determined by commercial kits and Western blot. Cell apoptosis, apoptotic-related protein (cleaved caspase-3, Bcl-2, and Bax) expression and protein kinase B (AKT) phosphorylation in vivo and in vitro were measured by TUNEL staining and Western blot. Finally, AKT blockage by 10 μM LY294002 or Nrf2 inhibition by10 μ M ML385 were utilized to prove the involvement of AKT and Nrf2/HO-1 pathway in AKI during sepsis.Results: We found Loganin treatment (20, 40, 80 mg/kg) mitigated septic AKI reflected by elevated renal function and palliative pathological changes. Oxidative stress and apoptosis in the kidney and LPS-treated HK2 cells were also inhibited by Loganin administration, which was accompanied by AKT and Nrf2/HO-1 pathway activation. Besides, the protective effects of Loganin could be diminished by AKT or Nrf2 blockage, indicating the involvement of AKT and Nrf2/HO-1 pathway.Conclusion: The results suggested that the protective effects of Loganin on AKI during sepsis might be mediated by AKT and Nrf2/HO-1 pathway signaling activation in kidney proximal tubular cells.Keywords: sepsis, acute kidney injury, Loganin, AKT, Nrf2/HO-1

The purpose of this work is to evaluate the performance of applying patient dosimetric information induced by individual uniform-intensity radiation fields in organ-at risk (OAR) dose-volume histogram (DVH) prediction, and extend to DVH prediction of planning target volume (PTV). Ninety nasopharyngeal cancer intensity-modulated radiation therapy (IMRT) plans and 60 rectal cancer volumetric modulated arc therapy (VMAT) plans were employed in this study. Of these, 20 nasopharyngeal cancer cases and 15 rectal cancer cases were randomly selected as the testing data. The DVH prediction was performed using two methods. One method applied the individual dose-volume histograms (IDVHs) induced by a series of fields with uniform-intensity irradiation and the other method applied the distance-to-target histogram and the conformal-plan-dose-volume histogram (DTH + CPDVH). The determination coefficient R2 and mean absolute error (MAE) were used to evaluate DVH prediction accuracy. The PTV DVH prediction was performed using the IDVHs. The PTV dose coverage was evaluated using D98, D95, D1 and uniformity index (UI). The OAR dose was compared using the maximum dose, V30 and V40. The significance of the results was examined with the Wilcoxon signed rank test. For PTV DVH prediction using IDVHs, the clinical plan and IDVHs prediction method achieved mean UI values of 1.07 and 1.06 for nasopharyngeal cancer, and 1.04 and 1.05 for rectal cancer, respectively. No significant difference was found between the clinical plan results and predicted results using the IDVHs method in achieving PTV dose coverage (D98,D95,D1 and UI) for both nasopharyngeal cancer and rectal cancer (p-values ≥ 0.052). For OAR DVH prediction, no significant difference was found between the IDVHs and DTH + CPDVH methods for the R2, MAE, the maximum dose, V30 and V40 (p-values ≥ 0.087 for all OARs). This work evaluates the performance of dosimetric information of several individual fields with uniform-intensity radiation for DVH prediction, and extends its application to PTV DVH prediction. The results indicated that the IDVHs method is comparable to the DTH + CPDVH method in accurately predicting the OAR DVH. The IDVHs method quantified the input features of the PTV and showed reliable PTV DVH prediction, which is helpful for plan quality evaluation and plan generation.

Background Preeclampsia is an idiopathic disease during pregnancy. This study explores the correlation between HLA-A polymorphism and the onset of preeclampsia. Methods The Illumina HiSeq2500 sequencing platform was used to genotyping HLA-A allele in venous blood DNA of 50 preeclampsia pregnant women and 48 normal pregnant women and umbilical cord blood DNA of their children of Han nationality in China. The frequencies and distributions of alleles and genotypes among the mothers and their children were compared between the two groups. The differences of frequencies and distributions of genotypes were compared between the two groups according to the mothers’ genotype compatibility. Results Twenty HLA-A alleles were detected in preeclampsia pregnant women and normal pregnant women; 21 HLA-A alleles were found in preeclampsia group fetuses and 22 HLA-A alleles in control group fetuses. There was no statistical difference in the HLA-A genes’ frequency between the two groups of pregnant women and their fetuses. When the sharing antigen was 1, the number of maternal-fetal pairs in the preeclampsia group was more than that in the control group; the difference was statistically significant (P P P = 0.0148); there is no significant difference in pregnant women’s genes homozygosity between early-onset preeclampsia group and the control group. Conclusions HLA-A * 24: 02 may be a susceptibility gene for early preeclampsia.

In this paper, an intelligent recognition system for insulator based on dimension correction and optimized faster region with convolutional neural network (R-CNN) is proposed. In the process of insulator pictures shooting, a laser radar is used to calculate the UAV correction vector. The position of the UAV is adjusted to ensure the consistency of the spatial dimensions of the pictures taken in different time dimensions. Based on the almost invariant spatial dimension, the faster R-CNN image recognition algorithm is optimized. When the target detection frame is generated, marked reference pictures are added to narrow the search range, improve the target detection frame generation speed, and reduce the number of pictures during training. Experiments and comparison analysis are included. They verify the optimized faster R-CNN image recognition algorithm requires less pictures and recognition time, and the recognition accuracy increased from 85.6 to 97.3%.

Objective This study investigated whether the delayed umbilical cord clamping can influence the pain during suturing perineal tears. Design This randomised controlled study applied the Consolidated Standards of Reporting Trials statement. Methods The sample comprised 288 pregnant women who gave birth through vaginal delivery in our hospital from November 2019 to December 2019. They were randomly divided into 2 groups-early umbilical cord clamping (n = 147) and delayed umbilical cord clamping (n = 141)-without severe pregnancy complications. There was no intrauterine infection, neonatal asphyxia or premature birth in the 288 newborns. The pain scores of the Numerical Rating Scale, Visual Analogue Scale, Verbal Rating Scale and Faces Pain Scale-Revised were used as indicators to evaluate the mothers' pain. The Mann-Whitney U test was used, and the statistical significance was set to p Result All indicators suggest that perineal suture pain of delayed umbilical cord clamping was lower than that of the control group. For the experience group, the perception of pain for the mothers who received analgesia was less than that for those who did not. For the control group, the Verbal Rating Scale suggests a statistical difference in suturing pain between acceptable and unacceptable labour analgesia. The degree of cooperation of the experience group was higher than that of the control group, but labour analgesia did not affect cooperation degree in both groups. Conclusion Delayed umbilical cord clamping can alleviate maternal pain when suturing perineal tears and improve the delivery experience. Labour analgesia can enhance the pain relief effect. Trial registration was performed on www.chictr.org.cn (ChiCTR1900026797). Relevance to clinical practice As a part of perinatal nursing, delayed umbilical cord clamping can help alleviate the pain of perineal suture and improve the experience of parturient. The method is simple and can be used as a routine nursing operation.

Background Listeriosis is a rare but severe foodborne infectious disease. Perinatal listeriosis is often associated with septicemia, central nervous system (CNS) infection, and serious adverse pregnancy outcomes (miscarriage and neonate death). Here we report the characteristics and outcomes of perinatal listeriosis cases treated over 6 years at Beijing Obstetrics and Gynecology Hospital (BOGH), the largest maternity hospital in China. Methods We retrospectively reviewed the records of laboratory-confirmed, pregnancy-associated listeriosis cases treated from January 1, 2013 to December 31, 2018. The clinical manifestations, laboratory results, perinatal complications and outcomes (post-natal follow-up of 6 months) were investigated. Results In BOGH, 12 perinatal listeriosis cases were diagnosed based on Listeria monocytogenes positive culture, including 10 single pregnancies and 2 twin pregnancies. The corresponding incidence of pregnancy-associated listeriosis was 13.7/100,000 deliveries. Among those cases, four pregnant women and four newborns had septicemia, and two of the neonates with septicemia also suffered CNS infection. All the maternal patients recovered. Two inevitable miscarriages and four fetal stillbirths occurred. Of the eight delivered newborns, six survived, and two died within 2 days from birth. None of the survivors had neurological sequelae during a 6-month follow-up. The overall feto-neonatal fatality rate was 57.1%; notably, this rate was 100% for infections occurring during the second trimester of pregnancy and only 14.3% for those occurring in the third trimester. Conclusions Perinatal listeriosis is associated with high feto-neonatal mortality, and thus, a public health concern. Additional large-scale studies are needed to strengthen the epidemiological understanding of listeriosis in China.

Valleytronics, based on the valley degree of freedom rather than charge, is a promising candidate for next-generation information devices beyond complementary metal–oxide–semiconductor (CMOS) technology1–4. Although many intriguing valleytronic properties have been explored based on excitonic injection or the non-local response of transverse current schemes at low temperature4–7, demonstrations of valleytronic building blocks similar to transistors in electronics, especially at room temperature, remain elusive. Here, we report a solid-state device that enables a full sequence of generating, propagating, detecting and manipulating valley information at room temperature. Chiral nanocrescent plasmonic antennae8 are used to selectively generate valley-polarized carriers in MoS2 through hot-electron injection under linearly polarized infrared excitation. These long-lived valley-polarized free carriers can be detected in a valley Hall configuration9–11 even without charge current, and can propagate over 18 μm by means of drift. In addition, electrostatic gating allows us to modulate the magnitude of the valley Hall voltage. The electrical valley Hall output could drive the valley manipulation of a cascaded stage, rendering the device able to serve as a transistor free of charge current with pure valleytronic input/output. Our results demonstrate the possibility of encoding and processing information by valley degree of freedom, and provide a universal strategy to study the Berry curvature dipole in quantum materials. A MoS2 transistor with chiral nanocrescent plasmonic antennae enables the generation, propagation, detection and manipulation of valley information at room temperature.

Early diagnosis of gastric cancer is difficult in China due to the lack of a valid method for endoscopic screening. Early gastric cancer, especially flat gastric cancer, lacks specific endoscopic features. Many cases appear to be similar to ordinary gastritis cases under normal white light endoscopy, which can lead to misdiagnosis. In order to find a new method to improve detection rate of early gastric cancer in China, we designed a trial to validate linked color imaging (LCI) for screening of early gastric cancer in a high-risk population, as compared to white light imaging (WLI). Subjects were randomly allocated to either the LCI + WLI or WLI group and then subjected to gastroscopy and all endoscopies were made after special preparation. All endoscopists had knowledge of this experiment. The main indicator was the rate of detection of gastric neoplastic lesions. The difference in the detection rate between the two groups is reported. The detection rate was 4.31% in the WLI group and 8.01% in the LCI + WLI group. This is a difference of 3.70% with a P value

Backgroud As the elderly stroke population continues to increase, we will have to confront greater challenges regarding how to choose suitable patients to reduce thrombolysis-related bleeding events and accurately judge their prognosis. Therefore, we evaluated the relationship among leukoaraiosis (LA), haemorrhagic transformation (HT) and the prognosis at 3 months after intravenous (IV) thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction (ACI). Methods We prospectively and consecutively chose 125 elderly patients aged ≥ 60 years with ACI who could accept and be suitable for IV recombinant tissue plasminogen activator (rtPA) after excluding 6 cases. Brain computed tomography(CT) was used to assess LA by using the modified Van Swieten scale (mVSS) before treatment and the modified Rankin scale (mRS) to appraise prognosis at 3 months after IV rtPA. Binary logistic regression was used to analyse the predictors of HT and the prognosis of ACI. Results Our data indicated that by brain CT, 26.4% of all patients showed severe LA, and the rate of HT and symptomatic intracranial haemorrhage (sICH) were 12.0% and 9.6%, respectively. Severe LA was evidently associated with HT (odds ratio [OR] 3.272, 95% confidence interval [CI] 1.010–10.598, P = 0.048) rather sICH (P > 0.05). Moreover, we also found that severe LA was associated with poor functional prognosis (OR 5.266, 95% CI 1.592–17.419, P = 0.006). Conclusion Our results showed that LA was associated with HT and adverse clinical prognosis rather sICH after IV rtPA in elderly patients aged ≥60 years with ACI. Although LA may increase the risk of bleeding but not fatal haemorrhage after IV thrombolysis, therefore, we should actively select an appropriate elderly population for thrombolytic treatment and have reasonable judgments on the outcomes.

Summary Background Immune checkpoint inhibitors targeting PD-1 have shown clinical benefit in adults with cancer, but data on these drugs in children are scarce. We did a phase 1–2 study of nivolumab, a PD-1 blocking monoclonal antibody, to determine its safety, pharmacokinetics, and antitumour activity in children and young adults with recurrent or refractory non-CNS solid tumours or lymphoma. Methods We did a multicentre, open-label, single-arm, dose-confirmation and dose-expansion, phase 1–2 trial in 23 hospitals in the USA. Eligible patients for part A (dose-confirmation phase) of the study were aged 1–18 years with solid tumours with measurable or evaluable disease (by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) regardless of histology. Eligible patients for part B (dose-expansion phase) were aged 1–30 years with measurable disease (by RECIST criteria) in the following disease cohorts: rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, Hodgkin lymphoma, non-Hodgkin lymphoma, and melanoma. Patients in part A and were given nivolumab 3 mg/kg intravenously over 60 min on days 1 and 15 of a 28-day cycle in a rolling 6 study design with de-escalation upon dose-limiting toxicities to establish the recommended phase 2 dose. Patients in part B were given the recommended phase 2 dose. The primary outcomes were the tolerability, systemic exposure, maximum tolerated dose, and the antitumour activity of nivolumab at the adult recommended dose in children and young adults. This trial is registered with ClinicalTrials.gov , NCT02304458 , with follow-up ongoing and is closed to new participants. Findings 85 patients were enrolled between Feb 22, 2015, and Dec 31, 2018, and 75 patients were fully evaluable for toxicity. Median follow-up was 30 days (IQR 27–83). In part A, 13 patients were enrolled and 12 were evaluable for toxicity. There were no dose de-escalations or dose-limiting toxicities and nivolumab 3 mg/kg was confirmed as the paediatric recommended phase 2. 72 patients were enrolled in part B and 63 were evaluable for toxicity. Five (7%) patients in part B had dose-limiting toxicities. The most common overall toxicity was anaemia (35 [47%] of 75 patients; five patients had grade 3 or grade 4) and non-haematological toxicity was fatigue (28 [37%] patients; none had grade 3 or grade 4). Responses were observed in patients with lymphoma (three [30%] of ten with Hodgkin lymphoma and one [10%] of ten with non-Hodgkin lymphoma; all responders had PD-L1 expression). Objective responses were not observed in other tumour types. Interpretation Nivolumab was safe and well tolerated in children and young adults and showed clinical activity in lymphoma. Nivolumab showed no significant single-agent activity in the common paediatric solid tumours. This study defines the recommended phase 2 dose and establishes a favourable safety profile for nivolumab in children and young adults, which can serve as the basis for its potential study in combinatorial regimens for childhood cancer. Funding Bristol-Myers Squibb, Children's Oncology Group, National Institutes of Health, Cookies for Kids Cancer Foundation.

As a new class of antitumor drugs, immune checkpoint inhibitors (ICIs) have shown remarkable efficacy toward the treatment of various malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed as immune‐related adverse events (irAEs) and unlike the adverse reactions of traditional therapies, irAEs are occult and not fixed, with some serious adverse reactions forcing patients to stop treatment which might even affect their survival. Therefore, with the wide clinical application of ICIs, clinicians need to fully understand the possible adverse reactions of these drugs and devise reasonable treatment strategies to improve the survival rate and therapeutic effects of patients receiving ICIs. In this article, we review the incidence, clinical manifestations, diagnosis and treatment of immune‐related endocrine events that may occur with the administration of ICIs.

Immunotherapy for malignant tumors is a hot spot in current research and the treatment of cancer. The activation of programmed cell death receptor‐1 (PD‐1) and cytotoxic T lymphocyte‐associated antigen 4 (CTLA)‐4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune‐checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune‐related adverse events (irAEs). The digestive system, including the gastrointestinal tract and liver which are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune‐related organs, is the most commonly affected system of irAEs. This review explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.

Background and objectives To analyze echocardiographic parameters of fetal large ventricular septal defect (VSD) and tetralogy of Fallot (TOF) in the context of multicenter data and big data analysis because these two diseases are often misdiagnosed in fetuses, and to find the key parameters for the differential diagnosis of these two diseases. Methods A total of 305 cases of large VSD and 192 cases of TOF diagnosed by fetal echocardiography from August 2010 to July 2016 from the database of Beijing Key Laboratory of Fetal Heart Defects were analyzed. Quantile regression of the 48 echocardiographic parameters of the 6272 normal fetuses from seven Chinese medical institutions was performed to determine the Q-score. The forward selection method and the naive Bayesian classification method were used to analyze the core differential diagnostic variables of fetal TOF and VSD. Results The Q-score of the internal diameter of the aorta (AO Q-score), the ratio of the diameter of the pulmonary artery to the internal diameter of the aorta (PA/AO), and the Q-score of the ratio of the diameter of the pulmonary artery to the internal diameter of the aorta (PA/AO Q-score) were key parameters for the differential diagnosis of fetal large VSD and TOF. PA/AO was the primary parameter, with an area under the receiver operating characteristic curve of 0.951. Conclusions These findings provide a new method for the prenatal diagnosis of large VSD and TOF and a theoretical basis for the intelligent diagnosis of large VSD and TOF.

Purpose: Adavosertib (AZD1775), an inhibitor of WEE1 kinase, potentiates replicative stress induced by oncogenes or chemotherapy. Antitumor activity of adavosertib has been demonstrated in preclinical models of pediatric cancer. This phase I trial was performed to define dose-limiting toxicities (DLT), recommended phase II dose (RP2D), and pharmacokinetics of adavosertib in combination with irinotecan in children and adolescents with relapsed or refractory solid tumors or primary central nervous system tumors. Patients and Methods: Using a 3+3 escalation design, five dose cohorts of the combination of adavosertib and irinotecan (50/70; 65/70; 65/90; 85/90; 110/90 mg/m2/day) delivered on days 1–5 of a 21-day cycle were studied. Pharmacokinetics and analysis of peripheral blood γH2AX was performed. Results: Thirty-seven patients were enrolled; 27 were evaluable. The median (range) age was 14 (2–20) years. Twenty-five (93%) received prior chemotherapy (median, three regimens) and 21 (78%) received prior radiotherapy. Eleven patients had a primary central nervous system (CNS) malignancy. Common toxicities were hematologic and gastrointestinal. Two patients receiving adavosertib (110 mg/m2) in combination with irinotecan (90 mg/m2) experienced dose-limiting grade 3 dehydration. A patient with Ewing sarcoma had a confirmed partial response and 2 patients (ependymoma and neuroblastoma) had prolonged stable disease (≥ 6 cycles). Pharmacokinetics of adavosertib were variable but generally dose proportional and clearance was lower in younger patients. Conclusions: Adavosertib (85 mg/m2) in combination with irinotecan (90 mg/m2) administered orally for 5 days was the MTD in children and adolescents with solid and CNS tumors.

L-shell X-ray fluorescence computed tomography based on polychromatic X-rays is a promising imaging technique for early cancer diagnosis. However, the presence of self-absorption and the long scanning time limit its usage in clinic. In this work, a reconstruction method based on split-Bregman algorithm which used sparseview projection data was proposed. Furthermore, the attenuation effect was also considered in the algorithm. In the attenuation correction, factors including the X-ray energy and the platinum concentration were taken into account. Then weighted factors calculated in the procedure of attenuation correction were added into the contribution function of pixels in the split-Bregman based reconstruction method. In the end, the feasibility of this method was tested using a cylindrical phantom with 8 mm in diameter by the Monte Carlo simulation. The phantom contained four inserts, all of which were 1.5 millimeter in diameter and filled with 0.10%, 0.20%, 0.40% and 0.80% platinum solutions, respectively. The results show that both the contrast-to-noise ratios and lowest detectable sensitivities are improved for the proposed method, comparing to the conventional MLEM. The contrast-to-noise ratios of images reconstructed by our method with 45 projections are already better than that reconstructed by MLEM with 60 projections. When using 60 projections in our method and comparing to 60 projections in the MLEM with correction, the contrast-to-noise ratio of the insert filled with 0.10% platinum solutions increased from 6.49 to 36.90, indicating its high efficiency and robustness.

Immune checkpoint inhibitors represent a major breakthrough in cancer therapy. Immune‐related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Management of irAEs is based on clinical experience because it is not easy to conduct prospective trials to evaluate the best treatment strategy. Using a combination of search terms in the PubMed and Embase databases, we reviewed all cases in the English language citing toxicities associated with either pembrolizumab, nivolumab, ipilimumab, atezolizumab, tremelimumab, durvalumab, avelumab or any combination of these agents published before 20 May 2019. A total of 128 reports with 239 cases were included in the study. Here, we summarize the spectrum of toxicities, safety in special patients, rechallenging after irAEs and agents used for treatment of irAEs in those reports.

We evaluated whether an irrigated contact force–sensing catheter would improve the safety and effectiveness of radiofrequency ablation of premature ventricular contractions originating from the right ventricular outflow tract. We retrospectively reviewed the charts of patients with symptomatic premature ventricular contractions who underwent ablation with a contact force–sensing catheter (56 patients, SmartTouch) or conventional catheter (59 patients, ThermoCool) at our hospital from August 2013 through December 2015. During a mean follow-up of 16 ± 5 months, 3 patients in the conventional group had recurrences, compared with none in the contact force group. Complications occurred only in the conventional group (one steam pop; 2 ablations suspended because of significantly increasing impedance). In the contact force group, the median contact force during ablation was 10 g (interquartile range, 7–14 g). Times for overall procedure (36.9 ± 5 min), fluoroscopy (86.3 ± 22.7 s), and ablation (60.3 ± 21.4 s) were significantly shorter in the contact force group than in the conventional group (46.2 ± 6.2 min, 107.7 ± 30 s, and 88.7 ± 32.3 s, respectively; P These findings suggest that ablation of premature ventricular contractions originating from the right ventricular outflow tract with an irrigated contact force–sensing catheter instead of a conventional catheter shortens overall procedure, fluoroscopy, and ablation times without increasing risk of recurrence or complications.

The increased use of targeted therapy and immune checkpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, increasing numbers of immune‐related adverse events (irAEs) of these medications have been reported, affecting almost all human organs including the eye. These adverse effects may affect the entire ocular region, including the eyelid, eye lashes, conjunctiva, cornea, uvea, retina and optic nerve, and have thus far been largely ignored by patients and doctors. In this review, we summarize the characteristics of ocular diseases related to irAEs and advise on how to diagnose and manage these diseases. Key points This review will enable clinical oncologists to recognize, diagnose, and manage targeted therapy and immune checkpoint inhibitor‐related ocular adverse events.

Background Isolated aortic brachiocephalic artery (IABA) is a rare congenital aortic arch anomaly. It is difficult to diagnose IABA prenatally and the prevalence in the prenatal population is unknown. Purpose To evaluate the echocardiographic characteristics and associations in fetuses with IABA. Material and Methods We retrospectively analyzed all cases of prenatal diagnosis of IABA from January 2012 to November 2020 and reviewed the follow-up results. Copy Number Variation Sequencing (CNV-Seq) was performed using the biological specimens of the of the fetuses and family members. Results Ten cases (10/45652, 0.022%) of IABA were identified in our center. The prevalence of the cases with isolated left subclavian artery (ILSCA) in the right aortic arch (RAA) population was 0.98% (6/613). The ILSCA was the most common isolated arch branch. All the isolated branches were on the opposite side of aortic arch in all the cases. The “ice stick” sign in the coronal section could be seen in most cases of IABA. Of the 10 cases, 8 (8/10, 80%) were associated with tetralogy of Fallot (TOF). Two cases of IABA were combined with 22q11.2 deletion syndrome. Conclusion IABA is a rare aortic anomaly. ILSCA was the most common isolated arch branch and TOF was the most common associated intra-cardiac anomaly. The “ice stick” sign in the coronal section could indicate a diagnosis of the IABA.

The tunneling magnetoresistance (TMR) with high-resolution digital output is widely used in military and civil fields. In this work we proposed a low-noise read-out circuit and a four-order fully differential sigma-delta modulator for TMR sensors. In the read-out circuit, we used symmetrical cascade for good matching. We used correlated double sampling (CDS) technique to improve the conversion accuracy of the modulator. In switched capacitor circuits we used time-division multiplexing to suppress charge injection and clock feedthrough. The high-precision application specific integrated circuit (ASIC) chip was fabricated by a 0.35 [Formula: see text]m CMOS process from Shanghai Huahong foundry. The TMR sensor was placed in an environment of three-layer magnetic shielding for test. The active area of the ASIC is only about [Formula: see text]. At a sampling frequency of 20 kHz, the TMR magnetometer consumes 77 mW from a single 5 V supply; the sigma-delta modulator for TMR can achieve an average noise floor of −141 dBV. The magnetometer works at a full scale (FS) of [Formula: see text], it can achieve a nonlinearity of 0.2% FS and a resolution of 0.15 nT/Hz[Formula: see text] over a signal bandwidth.

In this paper, a low-dimensional boron nitride nanoribbon with ultra-large aspect ratio was successfully prepared. Attractively, the singe BNNR, which carries the different metal electrode materials, exhibits excellent ohmic contact properties. The contact characteristics between single BNNR and Aurum electrode are better than Platinum electrode and Aluminum electrode. In addition, C-doping will change the semiconductor behavior of BNNR into metal behavior and the electrons have more chances to penetrate the barrier directly and reduce the ohmic contact resistance of the device which is of great significance in the design, assembly, and fabrication of high-performance semiconductor devices and the research of high-power radioresistance devices.

LinkedIn connects the world's professionals to make them more productive and successful. People Search plays an important role in fulfilling this goal by helping members find the most relevant and personalized results through a broad range of queries like names, job titles, skills, companies, locations, etc. It is one of the biggest search verticals at LinkedIn both in terms of engineering footprint and search traffic. In this paper, we present an overview of the People Search system, and discuss how we build and serve deep neural network (DNN) models, leveraging state-of-the-art deep natural language processing (NLP) techniques (e.g., convolutional neural networks (CNN) and Bidirectional Encoder Representations from Transformers (BERT)). We describe our journey of applying deep neural ranking models to a real-life product, including the modeling and system bottleneck challenges, crucial design choices, and lessons learned along the way. We hope a story of our endeavors and successes will provide meaningful insights to other similar systems.

Background: To investigate current knowledge, attitudes, and practices for CPR quality control among emergency physicians in Chinese tertiary hospitals.Methods: Anonymous questionnaires were distributed to physicians in 75 tertiary hospitals in China between January and July 2018.Results: A total of 1405 respondents answered survey without obvious logical errors. Only 54.4% knew all criteria of high-quality CPR. The main problems during CPR were related to chest compression: low quality due to fatigue (67.3%), inappropriate depth (57.3%) and rate (54.1%). 91.0% respondents considered CPR quality monitoring should be used, 72.4% knew objective method for monitoring, and 63.2% always/often monitored CPR quality during actual resuscitation. The utilization rate of recommended monitoring methods was reported as follow, ETCO2 was 42.7%, audio-visual feedback devices was10.1%, coronary perfusion pressure was 17.9%, and invasive arterial pressure was 31.1%. 96.3% respondents considered it was necessary to participate in regular CPR retraining, but 21.4% did not receive any retraining. The ideal retraining interval was considered to be 3 to 6 months, but actual interval was 6 to 12 months. CPR feedback devices were always/often used in training was reported by 49.7% of respondents.Conclusion: Chinese emergency physicians were very concerned about CPR quality, but they did not fully understand the high-quality criteria and impact on prognosis. CPR quality monitoring was not routine procedure during actual resuscitation. The methods recommended in guidelines were rarely used in practice. Many physicians have not received retraining or have received retraining at long intervals. Feedback devices were not commonly used in training.

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide but the incidence and its risk factors in China is limited. The objective of this study is to investigate the incidence and the risk factors of PPH in Chinese women.Methods: A multi-center retrospective study of pregnant women at ≥28 weeks of gestation was conducted. Logistic regression was used to identify potential risk factors of PPH and receiver operating characteristic curve was used to evaluate the predictive performance of the identified risk factors. Subgroup analysis focusing on the number of fetus and the mode of delivery was conducted.Results: A total of 99,253 pregnant women were enrolled and 804 (0.81%) experienced PPH. The subgroup analysis revealed that the incidence of PPH was 0.75, 2.65, 1.40, and 0.31% in singletons, twin pregnancies, cesarean sections, and vaginal deliveries, respectively. Placenta previa and placenta accreta were the predominant risk factors of PPH in the overall population and all subgroups. A twin pregnancy was a risk factor for PPH regardless of the mode of delivery. Obesity, and multiparity were risk factors for PPH in both singletons and cesarean section cases, but the latter predicted a reduced probability of PPH in vaginal deliveries. Macrosomia was associated with increased risk of PPH in singletons or vaginal deliveries. In women who delivered vaginally, preeclampsia was associated with a higher risk of PPH. The areas under the curve for the overall cohort, singletons, twin pregnancies, cesarean section cases, and vaginal deliveries were 0.832 (95% confidence interval [CI] 0.813–0.851), 0.824 (95% CI 0.803–0.845), 0.686 (95% CI 0.617–0.755), 0.854 (95% CI 0.834–0.874), and 0.690 (95% CI 0.646–0.735), respectively.Conclusions: The risk factors of PPH varied slightly based on the number of fetuses and the mode of delivery, while placenta previa and placenta accreta were the two major risk factors. A combination of the identified risk factors yielded a satisfactory predictive performance in determining PPH in the overall cohort, singletons pregnancies, and women who delivered by cesarean section, whereas the performance was moderate in twin pregnancies and in women delivering vaginally.

Background Fertility preservation using ovarian tissue cryopreservation (OTC) in patients with certain diseases, especially those needing chemo- or radiotherapy, is becoming routine in various Western countries. Our hospital is the first and until now the only centre in China to use this method. The question of whether treatment of breast cancer during pregnancy (PrBC) should be similar to non-pregnant young patients with breast cancer is controversial. To our knowledge, this is the first report worldwide to use OTC as fertility preservation for PrBC. Case presentation During the 29th week of pregnancy, a 24-year-old woman underwent needle aspiration cytology of a left breast tumour. Ultrasound and cytology revealed BI-RADS 4a grade. Oncologists recommended termination of the pregnancy. Caesarean section was performed at week 32, and ovarian tissue samples were collected for OTC to preserve fertility and ovarian endocrine function. Twenty-three ovarian cortex slices were cryopreserved. It is estimated that 13,000 follicles were cryopreserved. Breast nodules and sentinel lymph node biopsy suggested invasive micropapillary carcinoma. Neoadjuvant chemotherapy was started within 1 week after diagnosis. After six courses of neoadjuvant chemotherapy, targeted drug therapy and goserelin acetate, left mastectomy and left axillary lymph node dissection were performed. In total, 23 doses of radiotherapy, eight trastuzumab targeted therapy treatments, and 17 pertuzumab + trastuzumab double targeted therapy treatments were performed after breast cancer surgery. Until now, more than 2 years after delivery, the ovarian function still is good, and no signs of a negative impact of OTC have been observed. Goserelin acetate injections, administered every 28 days, are planned to last for the next 5 years. In addition, endocrine therapy with anastrozole was started after breast cancer surgery and also is scheduled for 5 years. Conclusion OTC for fertility preservation in patients with PrBC does not delay breast surgery, radiotherapy or chemotherapy, which is essential for effective treatment of breast cancer. We assess this method as a promising fertility preservation method which was used here for the first time worldwide in a patient who developed breast cancer during pregnancy.

Background: Thoracoscopic diaphragmatic plication has gained popularity in the treatment of congenital diaphragmatic eventration (CDE), but the therapeutic effect and prognosis have rarely been com...

Small intestinal bacterial overgrowth (SIBO) is characterized by abnormal and excessive amounts of bacteria in the small intestine. Since symptoms and lab tests are non-specific, the diagnosis of SIBO is highly dependent on breath testing. There is a lack of a universally accepted cut-off point for breath testing to diagnose SIBO, and the dilemma of defining “SIBO patients” has made it more difficult to explore the gold standard for SIBO diagnosis. How to validate the gold standard for breath testing without defining “SIBO patients” has become an imperious demand in clinic. Breath-testing datasets from 1071 patients were collected from Xiangya Hospital in the past 3 years and analyzed with an artificial intelligence method using cluster analysis. K-means and DBSCAN algorithms were applied to the dataset after the clustering tendency was confirmed with Hopkins Statistic. Satisfying the clustering effect was evaluated with a Silhouette score, and patterns of each group were described. Advantages of artificial intelligence application in adaptive breath-testing diagnosis criteria with SIBO were discussed from the aspects of high dimensional analysis, and data-driven and regional specific dietary influence. This research work implied a promising application of artificial intelligence for SIBO diagnosis, which would benefit clinical practice and scientific research.

Purpose: To investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD). Methods: A total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD.Results: Male predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland.Conclusions: Lacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.