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Convolutional neural networks (CNN) based object detection usually assumes that training and test data have the same distribution, which, however, does not always hold in real-world applications. In autonomous vehicles, the driving scene (target domain) consists of unconstrained road environments which cannot all possibly be observed in training data (source domain) and this will lead to a sharp drop in the accuracy of the detector. In this paper, we propose a domain adaptation framework based on pseudo-labels to solve the domain shift. First, the pseudo-labels of the target domain images are generated by the baseline detector (BD) and optimized by our data optimization module to correct the errors. Then, the hard samples in a single image are labeled based on the optimization results of pseudo-labels. The adaptive sampling module is approached to sample target domain data according to the number of hard samples per image to select more effective data. Finally, a modified knowledge distillation loss is applied in the retraining module, and we investigate two ways of assigning soft-labels to the training examples from the target domain to retrain the detector. We evaluate the average precision of our approach in various source/target domain pairs and demonstrate that the framework improves over 10% average precision of BD on multiple domain adaptation scenarios on the Cityscapes, KITTI, and Apollo datasets.

Glioblastoma (GB) is the most lethal form of primary brain neoplasm. TMZ is the first-line standard treatment, but the strong resistance constrains the efficacy in clinical use. GB contains glioma stem cells (GSCs), which contribute to TMZ resistance, promote cell survival evolvement, and repopulate the tumor mass. This review summarizes the TMZ-resistance mechanisms and discusses several potential therapies from the conservative opinion of GSC-targeted therapy orientation to the current view of TMZ resistance-aimed efficacy, which will provide an understanding of the role of heterogeneity in drug resistance and improve therapeutic efficacy in general.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P

Improvements to the dynamic characteristics and stiffness of composite girder bridges are necessary to expand their applications and capabilities. The natural frequency of a bridge directly reflects the dynamic characteristics of a structure. From the calculation principle for the natural frequency, the natural frequencies of a bridge can be significantly increased if the load increases slightly while the structural stiffness increases significantly. Based on this, a new type of concrete-steel composite truss bridge is proposed. The new bridge has a reasonable new arrangement for the position of the concrete and steel, according to the bending moment law for continuous girders. The mechanical analysis of the new bridge shows that it has the characteristic of adding a small amount of load at a reasonable position, which can significantly improve the stiffness. Therefore, it is possible to achieve the purpose of improving the dynamic characteristics so that they are far better than those of a conventional composite truss bridge. To further study the dynamic characteristics of the new composite truss bridge, the finite element (FE) method was used to analyse the new bridges, and the results are compared with those of conventional composite truss bridges. Furthermore, several parameters that influence the dynamic characteristics of the new composite truss bridge were studied. Finally, the dynamic characteristics of the small-span new bridge were studied by finite element analysis (FEA) and experiment. The results show that the new composite truss bridges with different span arrangements and different second-stage dead loads always have better natural frequencies and stiffness advantages. Therefore, the new composite truss bridge is suitable for girder bridges with strict requirements for their stiffness and dynamic characteristics, especially for super-long span high-speed railway girder bridges.

Significance Although the overwhelming majority of COVID-19-related deaths are due to respiratory failure, little is known about the host response to SARS-CoV-2 in lung parenchyma. By profiling the lung and colon transcriptome and lung proteome of nine patients who died of COVID-19 during the first wave of the pandemic in Wuhan, China, we obtained molecular insights into the host response to severe SARS-CoV-2 infection. Interestingly, all samples had a low viral burden, a finding that suggests the patients’ deaths may be due to uncontrolled host inflammatory processes rather than an active viral infection. Taken together, our findings shed light on COVID-19 pathophysiology and offer potential therapeutic targets for severe COVID-19 disease., Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

High-throughput RNA sequencing unveiled the complexity of transcriptome and significantly increased the records of long noncoding RNAs (lncRNAs), which were reported to participate in a variety of biological processes. Identification of lncRNAs is a key step in lncRNA analysis, and a bunch of bioinformatics tools have been developed for this purpose in recent years. While these tools allow us to identify lncRNA more efficiently and accurately, they may produce inconsistent results, making selection a confusing issue. We compared the performance of 41 analysis models based on 14 software packages and different data sets, including high-quality data and low-quality data from 33 species. In addition, computational efficiency, robustness, and joint prediction of the models were explored. As a practical guidance, key points for lncRNA identification under different situations were summarized. In this investigation, no one of these models could be superior to others under all test conditions. The performance of a model relied to a great extent on the source of transcripts and the quality of assemblies. As general references, FEELnc_all_cl, CPC, and CPAT_mouse work well in most species while COME, CNCI, and lncScore are good choices for model organisms. Since these tools are sensitive to different factors such as the species involved and the quality of assembly, researchers must carefully select the appropriate tool based on the actual data. Alternatively, our test suggests that joint prediction could behave better than any single model if proper models were chosen. All scripts/data used in this research can be accessed at http://bioinfo.ihb.ac.cn/elit.

Atrial fibrillation (AF) is the most common arrhythmia among the elderly, and more frequently occur in those with chronic kidney disease (CKD). Left atrial appendage occlusion (LAAO) is used as a mechanical alternative approach for prevention of AF-related thromboembolisms. This meta-analysis was conducted to provide suggestions for the clinical application of LAAO in AF patients with CKD. The incidence of perioperative adverse events and other clinical effects after operation was by a single rate meta-analysis. Results showed that incidence of adverse events in the perioperative period after LAAO was generally low, with only pericardial effusion / tamponade (1.90%) and mortality rate (1.10%). During the follow-up period, the incidence of stroke/transient ischemic attack (TIA) and bleeding were 2.17% and 4.53%, respectively. A low incidence rate of adverse events was found in the perioperative period following LAAO. These results indicate that LAAO more effectively prevents the occurrence of stroke/TIA and minimizes bleeding events than oral anticoagulants.

Based on the dual-path cancellation methodology, a noise cancellation technique and an insertion loss (IL) mitigation technique are presented to improve the properties of the active quasi-circulators. The proposed circulator is fabricated with a standard 0.18- $\mu \text{m}$ CMOS process, occupying an area of 0.91 $\text {mm} \times 0.49$ mm including the pads. The measurement results show that 34-dB isolation is obtained over a wide frequency range from 1 to 8 GHz, while the IL is below 2.5 dB and the noise figure (NF) is less than 10 dB.

In this paper, bidirectional Long Short-Term Memory (BiLSTM) networks are designed to realize the semantic segmentation of QRS complex in single channel electrocardiogram (ECG) for the tasks of R peak detection and heart rate estimation. Three types of seq2seq BiLSTM networks are introduced, including the densely connected BiLSTM with attention model, the BiLSTM U-Net, and the BiLSTM U-Net++. To alleviate the sparse problem of the QRS labels, symmetric label expansion is applied by extending the single R peak into a time interval of fixed length. Linear ensemble method is introduced that averages the outputs of different BiLSTM networks. The cross-validation results show significant increase of the accuracy and decrease of discontinuous gaps in the QRS interval prediction by the ensembling over singular neural networks.

ObjectiveGraves’ disease (GD) related hyperthyroidism (HT) has profound effects on metabolic activity and metabolism of macromolecules affecting energy homeostasis. In this study, we aimed to get a comprehensive understanding of the metabolic changes and their clinical relevance in GD children.MethodsWe investigated serum substances from 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We explored the metabolomics using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis, and then analyzed the metabolomic data via multivariate statistical analysis.ResultsBy untargeted metabolomic analysis, a total of 730 metabolites were identified in all participants, among which 48 differential metabolites between GD and control groups were filtered out, including amino acids, dipeptides, lipids, purines, etc. Among these metabolites, 33 were detected with higher levels, while 15 with lower levels in GD group compared to controls. Pathway analysis showed that HT had a significant impact on aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis, several amino acids metabolism, purine metabolism, and pyrimidine metabolism.ConclusionIn this study, via untargeted metabolomics analysis, significant variations of serum metabolomic patterns were detected in GD children.

BackgroundHashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis.MethodsExperimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined.ResultsHT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons.ConclusionOur results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

Background:Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown.Objectives:To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, bothin vivoandin vitro.Methods:We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group.Results:Thein vivoandin vitroresults showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3.Conclusion:miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.

Graves’ disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds via ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor (p = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset (p = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.

BackgroundIn recent years, immune checkpoint inhibitors have shown significant effects in a variety of solid tumors. However, due to the low incidence of small cell lung cancer (SCLC) and its unclear mechanism, immune checkpoints in SCLC have not been fully studied.MethodsWe evaluated the expression of PD-L1, B7-H3, and B7-H4 in 115 SCLC tissue specimens using immunohistochemistry. The clinical data of patients with SCLC were retrospectively reviewed to investigate three negative co-stimulatory B7 family molecules’ ability to affect the prognosis of SCLC.ResultsAmong the SCLC patients with complete follow-up data (n = 107), sixty-nine (64.49%) expressed moderate to high B7-H3 levels, which correlated positively with tumor sizes (P < 0.001). Eighty (74.77%) patients expressed moderate to high B7-H4 levels, which correlated positively with metastases (P = 0.049). The positive expression of B7-H3 and B7-H4 correlated significantly with shortened overall survival (OS) (B7-H3, P = 0.006; B7-H4, P = 0.019). PD-L1 was positively expressed only in 13.08% of cancer tissues, and there was no significant correlation with prognosis. The Cox proportional hazards regression showed that B7-H3 was an independent prognostic indicator of OS (P = 0.028; HR = 2.125 [95% CI = 0.985-4.462]).ConclusionsOur results suggest that B7-H3 has a negative predictive effect on SCLC. This outcome provides a theoretical basis for the subsequent research on immune checkpoint inhibitors targeting B7-H3.

BACKGROUND Joint stiffness after elbow surgery is not a rare complication, and is always accompanied by deformity. The causes of joint stiffness are multiple in different patients, and divided into intrinsic and extrinsic causes. Herein, we report an unusual case of posttraumatic elbow stiffness due to multiple and rare causes. CASE SUMMARY A 19-year-old male was hospitalized with the loss of motion of the left elbow for over ten years. Left limb computed tomography revealed left elbow stiffness with bony block and connection. The patient underwent surgery, and the etiology of joint stiffness was found to be a rare combination of common and uncommon causes. During an 18-mo follow-up period, the patient’s left elbow had normal motion and he was symptom-free. CONCLUSION However, this case combined with multiple and rare causes highlights that the patient with scar physique is likely to be accompanied with more severe soft tissue, nerve contracture, and heterotypic ossification, even during recurrence.

BackgroundPatients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty.MethodsFifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications.ResultsFifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6–12 and 12–18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment:P P ConclusionsOur study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose.Trial registrationThe study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry:ChiCTR2000038686.

Background: The pandemic of coronavirus disease (Covid-19) seriously impacts the health and well-being of all of us. Aims: We aim to assess the psychological impact of Covid-19 on frontline health care workers (HCWs), including anxiety, depression and stress of threat of the disease. Method: The study was a cross-sectional survey among the frontline HCWs in a hospital at Jinan, China. Data were collected through an anonymous, self-rated questionnaire, including basic demographic data, a 10-item Covid-19 stress questionnaire, the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS). The risk and rate of anxiety, depression and stress of Covid-19 were estimated. Results: Among the 309 participants, there were 88 (28.5%) with anxiety and 172 (56.0%) with depression. Multivariate logistic regression analyses showed that age ⩽ 30 years, age > 30 to 45 years, working in confirmed case isolation wards, and worrying about disinfection measures being not sufficient were independently associated with anxiety with an odds ratio (95% confidence interval, CI) of 4.4 (1.6–12.2), 3.1 (1.1–8.8), 2.3 (1.4–4.0) and 2.5 (1.5–4.3), respectively; age ⩽ 30 years, age > 30 to 45 years, nurse and worrying about disinfection measure being not sufficient were independently associated with depression with an odds ratio (95% CI) of 3.8 (1.8–7.8), 2.7 (1.3–5.7), 2.5 (1.1–5.6) and 2.1 (1.3–3.5), respectively. Conclusions: A high prevalence of anxiety and depression was found among frontline HCWs during the COVID-19 outbreak. More psychological care should be given to young staffs and nurses. Measures to prevent professional exposure is important for HCWs’ physical and mental health.

Glioblastoma (GBM) is highly invasive and the deadliest brain tumor in adults. It is characterized by inter-tumor and intra-tumor heterogeneity, short patient survival, and lack of effective treatment. Prognosis and therapy selection is driven by molecular data from gene transcription, genetic alterations and DNA methylation. The four GBM molecular subtypes are proneural, neural, classical, and mesenchymal. More effective personalized therapy heavily depends on higher resolution molecular subtype signatures, combined with gene therapy, immunotherapy and organoid technology. In this review, we summarize the principal GBM molecular classifications that guide diagnosis, prognosis, and therapeutic recommendations.

OBJECTIVE Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure. Cardiac hypertrophy is mostly considered reversible, and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension, but also achieves therapeutic effects by blocking fibrosis-related signaling pathways. However, the mechanism of action of decorin remains unknown and unconfirmed. METHODS We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight, histological analysis and immunohistochemistry. Western blotting was performed to detect the expression levels of CaMKII, p-CaMKII and MEF-2 in the heart. RESULTS Our results confirmed that decorin can regulate the CaMKII/MEF-2 signaling pathway, with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy. CONCLUSION Taken together, the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKII/MEF-2 signaling pathway in vivo, revealing a new therapeutic approach for the prevention of cardiac hypertrophy.

Objectives Graves’ disease (GD) is an autoimmune disease involving intimate response of both T cells and B cells. Immunophenotyping of peripheral blood lymphocyte subsets in GD children with different clinical characteristics can provide further information of the pathogenesis of GD. Methods We studied the lymphocyte subsets in peripheral blood of 141 children with GD. We repeatedly divided the patients into two groups in accordance with different clinical characteristics (abnormal or normal alanine aminotransferase (ALT) levels, the presence or absence of Graves’ orbitopathy (GO), and the presence or absence of hematuria. Then we compared the lymphocyte subsets measurements between two paired groups. Results We found that serum ALT levels correlated positively with CD3+CD8+ T cell percentages in children with GD. Moreover, we detected higher percentages of CD3−CD19+ cells and higher ratio of CD4/CD8 in patients with GO. However, no correlation was found between GO status and lymphocyte subsets after excluding confounding effect of TRAb. No difference of lymphocyte subset percentages was found between groups with or without hematuria. Conclusions Serum ALT levels correlate positively with cytotoxic T cell percentages in the peripheral blood of children with GD. The cytotoxic T cell may play a role in the pathogenesis of hepatic dysfunction in children with GD.

Background Erdheim-Chester disease (ECD) is a rare multi-system or multi-organ histiocytic proliferative disease with diverse clinical manifestations, and the development of the disease is complex, which makes clinical diagnosis and treatment difficult. The characteristic clinical manifestations include multi-organ involvement, especially in the symmetrical diaphysis and metaphysis of the bilateral extremities. ECD with a unilateral talus lesion is extremely rare. Here, we report an unusual case of ECD invading the asymmetric talus and tibia without involving other organs. The patient had good outcome after surgery. Case summary We report a case of a 67-year-old man who was referred to our outpatient department because of left ankle chronic pain for 5 years, which exacerbated after a foot sprain 6 mo previously. We discovered multiple sclerotic lesions of the tibia and talus on his previous X-ray films, which were initially missed in a local hospital. Therefore, enhanced computer computed tomography (CT) and magnetic resonance imaging were performed. These examinations showed multiple lesions in the bone marrow cavity of the left tibia, and cortical sclerosis and osteonecrosis of the left talus. Specimens were collected via bone puncture from the two lesions, and a final diagnosis of ECD was confirmed by pathological and immunohistochemical examinations. In addition, other auxiliary examinations including head CT, pulmonary CT, spinal CT, abdominal CT, cardiac ultrasound and thyroid ultrasound showed no obvious abnormalities. The patient underwent surgery for the tibia lesion scraping and talus lesion scraping combined with cement casting. The patient started on a progressive rehabilitation at 4 wk, and felt no pain after surgery. During a 2-year follow-up period, the patient exercised normally without pain, and there were no signs of recurrence. Conclusion This study shows that surgery treatment may also achieve good results for ECD patients with only bone involvement.

Breast cancer is one of the most common and fatal cancers in women today. To detect the differential features for correctly diagnosing breast cancer patients, a 2D feature selection algorithm is proposed in this paper. It is named as SDP for short because it adopts the Standard Deviation and Pearson correlation coefficient to define the feature discernibility and independence respectively. The feature importance is defined as the product of its discernibility and independence. A 2D space is constructed using discernibility as x-axis and independence as y-axis. The area of the rectangular enclosed by a feature coordinate lines and axes implies the importance of the feature. Those features in the upper right corner of the 2D space are with much higher importance than the rest ones. They comprise the differential feature subset. The spectral clustering algorithms SC_SD and SC_MD are adopted for clustering analysis, so the two algorithms SDP+SC_SD and SDP+SC_MD were developed for clustering analysis to the breast cancer data WBCD (Wisconsin Breast Cancer Database), WDBC (Wisconsin Diagnostic Breast Cancer), and WPBC (Wisconsin Prognostic Breast Cancer). The experimental results demonstrate that the proposed SDP can detect much better differential features of breast cancers than other compared feature selection algorithms, and the SDP+SC_SD and SDP+SC_MD algorithms outperform the algorithms without feature selection process embedded, such as SC_SD, SC_MD, DPC, SD_DPC, K-means and SD_K-medoids in terms of clustering accuracy, AMI (Adjusted Mutual Information), ARI (Adjusted Rand Index), sensitivity, specificity and precision.

BACKGROUND Sepsis causes the highest mortality in non-cardiovascular intensive care units worldwide. Recent research has demonstrated that the late phase of sepsis, characterized as septic immunosuppression, is the central pathophysiological mechanism of immune dysfunction. Investigating the suppressive mechanism of immune cells may identify possible targets for therapy. MATERIAL AND METHODS We used LPS 2-hit model for dendritic cells (DCs) to establish endotoxin tolerance, and co-cultured with splenocytes. Co-culture responses and gene expressions were evaluated. RESULTS Endotoxin tolerant DCs showed irresponsiveness in pro-inflammatory cytokine production and expressed negative regulator genes of inflammation. When co-cultured with splenocytes, suppression of inflammatory responses and T cells apoptosis were observed with elevated expression of IRAK-M and PDL-1, and interference and neutralization of these 2 molecules led to partly reversed suppression of inflammation. CONCLUSIONS Our research found direct regulation of endotoxin tolerant DCs to other immune cells and suggested a possible mechanism via IRAK-M and PDL-1. This may inform research on septic immunosuppression and suggests possible therapeutic targets for sepsis.

With the expanding of marine and freshwater aquaculture, the outbreaks of aquatic animal diseases have increasingly become the major threats to the healthy development of aquaculture industries. Notably, viral infections lead to massive fish deaths and result in great economic loss every year across the world. Hence, it is meaningful to clarify the biodiversity, geographical distribution and host specificity of fish-associated viruses. In this study, viral sequences detected in fish samples were manually collected from public resources, along with the related metadata, such as sampling time, location, specimen type and fish species. Moreover, the information regarding the host fish, including aliases, diet type and geographic distribution were also integrated into a database (FVD). To date, FVD covers the information of 4860 fish-associated viruses belonging to 15 viral families, which were detected from 306 fish species in 57 countries. Meanwhile, sequence alignment, live data statistics and download function are available. Through the user-friendly interface, FVD provides a practical platform that would not only benefit virologists who want to disclose the spread of fish-associated viruses, but also zoologists who focus on the health of domestic and wild animals. Furthermore, it may facilitate the surveillance and prevention of fish viral diseases. Database URL: http://bioinfo.ihb.ac.cn/fvd.

Cryptococcosis is an infection caused by the yeast-like fungus Cryptococcus neoformans. Pulmonary cryptococcosis is typically identified as a single mass or as multiple nodules, while endobronchial lesions are quite rare. Here we report an uncommon case of pulmonary cryptococcosis presenting as endobronchial lesion in an immunocompetent patient. A 49-year-old male patient complained of intermittent cough with hemoptysis for two years. Computerized tomography of the chest showed a filling defect in the basal segment of the right lower lobe bronchus. A flexible bronchoscopic examination revealed a white smooth-surfaced polypoid lesion completely occluding the medial basal segment of the right lower lobe bronchus. The diagnosis was confirmed by bronchial biopsy under bronchoscopy, and the histopathologic findings showed the organisms were Cryptococcal neoformans. The patient was treated with fluconazole at a dose of 400 mg daily. The endobronchial lesion was found rapidly diminished after 18 days of therapy, and disappeared after 6.5 months of therapy by repeated fiberoptic bronchoscopy. Then the patient continued fluconazole for another 2.5 months. During the total 16 months' follow-up visits, the patient repeated CT scanning for five times, the results of which were all normal. The patient's symptoms disappeared as well, and now he is still under follow-up. This case highlights the fact that pulmonary cryptococcosis can present as endobronchial lesions even in immunocompetent subjects, mimicking lung tumor. Pathological confirmation is important to establish the definite diagnosis. Keywords: Case report, Cryptococcosis, Endobronchial mass, Pulmonary cryptococcosis

Circulator is a key component in full-duplex wireless and radar detection systems. In this letter, a dual interference-canceling active quasi-circulator is proposed to enhance the isolation capability over the range of 1–7 GHz. The circulator is fabricated in the standard 0.18- $\mu \text{m}$ CMOS process occupying 1.03 mm $\times0.55$ mm including the pads. Measurement results demonstrate more than 36-dB isolation from the Tx to the Rx within 6-GHz bandwidth. The designed circulator is a good candidate for duplexers to allow the integrated transmitter and receiver to share a single antenna in the certain short-range wideband wireless communication systems, where noise figure (NF) is not strictly demanded but low cost and high integration are urgently required.

The platooning of automated vehicles has potential to significantly benefit road traffic, while its robust performance is less investigated especially considering increasing complexity of interaction topologies. This study presents a decoupled H ∞ control method for automated vehicular platoon to comprehensively compromise multiple performances. The platoon control system is first decomposed into an uncertain part and a diagonal nominal system through the linear transformation, which is motivated by the eigenvalue decomposition of information topology. Based on this almost decoupled system, a distributed H ∞ controller is presented, which can balance the performances of robustness and disturbance attenuation ability. Moreover, a numerical method is given to solve and optimise this controller by using linear matrix inequality approach. Several comparative hardware-in-loop tests of different communication topologies and controllers have been carried out to demonstrate the effectiveness of this method.

BackgroundAlthough thyroid dysfunction caused by Hashimoto’s thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice.MethodsFemale NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot.ResultsHT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin β3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found.ConclusionsThese findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.

This paper presents a direct voltage detection architecture that can be used for linear envelope detectors. A preamplifier using a common-gate (CG) common-source (CS) circuit topology sends the input modulated signal to a differential output and is coupled to a pair of common source stages. By using the quadratic IV curve of the MOSFETs, the detector can achieve linear operations on the detected envelope signals. The envelope detector was designed using a standard 0.18 $\mu n$ CMOS process. The simulation result shows the detector can track a 120 MHz modulation signal at cost of 18 mW of static power with a 1.8 V power supply.

Adult-onset hypothyroidism induces cognitive impairments in learning and memory. Thyroxin (T4) replacement therapy appears to be effective in biochemically restoring euthyroidism, as evidenced by serum T4 and triiodothyronine concentrations within the normal range, although some the patients still exhibit cognitive dysfunctions. Here, we investigated the cognitive functions of propylthiouracil-induced hypothyroid mice in C57BL/6j and 129/Sv strains using the passive avoidance task and the novel object recognition test. Cognitive dysfunctions in hypothyroid mice were found only in the C57BL/6j strain, not in the 129/Sv strain. Further, we found that cholinergic neurons in the basal forebrain increased the membrane potential and input resistance with decreased capacitance, and that they decreased the amplitude and width of action potential in hypothyroid mice in the C57BL/6j strain but not in those in the 129/Sv strain, compared with the controls for each strain. Additionally, the excitability of cholinergic neurons in the basal forebrain was reduced in the hypothyroid mice in the C57BL/6j strain. These results indicated that transgenic mice with the C57BL/6j genetic background are more suitable for revealing the mechanism underlying hypothyroidism-induced cognitive dysfunction, and that the cholinergic basal forebrain may be the appropriate target for treating cognitive dysfunction in adult-onset hypothyroidism.

In this paper, we present a 5-GHz high efficiency class-E power amplifier. Due to zero voltage switching and zero voltage derivative switching conditions, class-E power amplifiers (PAs) are highly efficient. But the reliability of device caused by excessively high peak voltages should be considered carefully. In order to alleviate the device stress, a triple-stacked class-E PA with proposed dynamic biasing network is presented, which can divide the voltage stress equally among three transistors. The supply voltage of the proposed PA is increased compared to common source or cascode class-E PA, which enhances the efficiency of class-E PA. Because of the high supply voltage and operating frequency of 5 GHz, the proposed class-E PA requires small shunt capacitance, which limits the transistor size. The proposed parallel resonant inductor breaks this limitation and avoids the power loss caused by the large on-resistance of small-sized transistors. The proposed PA is implemented in a 0.18 μm CMOS process with the chip area of 0.235 mm2. Simulation results show that the PA achieves 49.5% power-added efficiency (PAE) and 53.7% drain efficiency while delivering peak output power of 22.3 dBm at 5 GHz.

Candida haemulonii forms part of the non-albicans Candida species. The candidemia caused by C. haemulonii is extremely rare but fatal in neonates. We reported the first two neonates with C. haemulonii candidemia in China which were treated with fluconazole and reviewed two papers previously reported. Our report adds further awareness on C. haemulonii candidemia in critical neonates and points out the importance of an early diagnosis and treatment of this fatal infection.La Candida haemulonii forma parte de la especie Candida no albicans. La candidemia por C. haemulonii es sumamente infrecuente, pero mortal, en los recién nacidos. Se informa sobre los dos primeros recién nacidos con candidemia por C. haemulonii en China tratados con fluconazol y se revisan dos artículos informados con anterioridad. Nuestro informe incrementa la sensibilización sobre la candidemia por C. haemulonii en recién nacidos críticos y resalta la importancia de un diagnóstico y un tratamiento tempranos de esta infección mortal.

Sepsis is the leading cause of mortality in intensive care units due to complex inflammatory immune responses and immunosuppression. Recent studies have indicated that the negative regulator of toll like receptors, interleukin-1 receptor-associated kinase 3 (IRAK-3/IRAK-M), serves an important role in immunosuppression during sepsis. In the current study, a cecal ligation puncture model was established in mice using lipopolysaccharide secondary challenge to simulate immunosuppression in sepsis. Peripheral blood mononuclear cells (PBMCs) from this model were then used to evaluate the expression and function of IRAK-M. The results demonstrated that silencing of IRAK-M expression in PBMCs from immunosuppressed mice partially restored the production of pro-inflammatory cytokines. By introducing PBMCs transfected with small-interfering RNA targeting IRAK-M into septic immunosuppressed mice, the survival rate was improved with an increase in splenic CD4+ and CD8+ T cells and a decrease in T cell apoptosis. In conclusion, downregulation of IRAK-M reversed the effects of sepsis on the production of inflammatory cytokines in PBMCs, and improved the survival of septic immunosuppressed mice. These results provide a basis for future studies investigating the immunological mechanisms underlying immune suppression in sepsis.

The grass carp is an important farmed fish, accounting for similar to 16% of global freshwater aquaculture, and has a vegetarian diet. Here we report a 0.9-Gb draft genome of a gynogenetic female adult and a 1.07-Gb genome of a wild male adult. Genome annotation identified 27,263 protein-coding gene models in the female genome. A total of 114 scaffolds consisting of 573 Mb are anchored on 24 linkage groups. Divergence between grass carp and zebrafish is estimated to have occurred 49-54 million years ago. We identify a chromosome fusion in grass carp relative to zebrafish and report frequent crossovers between the grass carp X and Y chromosomes. We find that transcriptional activation of the mevalonate pathway and steroid biosynthesis in liver is associated with the grass carp's adaptation from a carnivorous to an herbivorous diet. We believe that the grass carp genome could serve as an initial platform for breeding better-quality fish using a genomic approach.

Objective To observe the effect of acupoint massage in relieving pain after ureteroscopic holmium laser lithotripsy.

Aiming at existing problems in practical teaching of Environmental Engineering specialty at present, the contradiction between the professional comprehensive quality of the students and the employing demands of the enterprise, to improve the students' innovative thinking and engineering application ability, combining with the special features of the school and the advantage of the environmental engineering training base, we construct practical teaching system of environmental engineering specialty and put forward reform measures of the "three combination", "four module" and "five platform", reforming and exploring the teachers’ teaching methods and students' cultivating system under the new background of engineering practical teaching system. In recent years, with the development of ecological civilization construction in depth, People’s requirements on environmental protection and environmental quality become more and more sensitive. Therefore, the environmental engineering professionals face with more opportunities and greater challenges. How to make students not only have a solid basic knowledge but also have some practical experience in engineering to meet the times' urgent needs for high-quality environmental engineering talent, which is undoubtedly an extremely significant research topic. This study analyzes the existing problems in the practical teaching links of environmental engineering at present and tries to reform and explore it from mufti-angle such as the teaching cultivating system, teaching method and cultivating mode.

Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.

Purpose：By investigating the variation of the human walking gait kinematics with respect to the foot deformation constraint, prove that bionic design of feet are the necessity for biped robots to imitate human walking better in terms of flexibility, stability and efficiency. The results will be significant for future research and development of biped robots. Methods: A human being was assumed as a perfect biped robot which had ideal motion drive and control. The walking gait parameters of two healthy men with foot deformation unconstrained and constrained were tested respectively by the inertia motion capture suit, and then they were processed by programming and analyzed by comparison. Results: The data analysis showed that when subjects walked with foot deformation constrained, their angular displacements of lower limb joints generally increased, the curves of angular velocity and accelerations fluctuated in certain walking phases, the walking pace and stride length decreased obviously, the single support phase shortened while the double support phase lengthened. At the same time, subjects felt subjectively that their body motion was less flexible, the walking posture was difficult to control, and the walking stability was more strenuous to keep. Conclusion: Combining the logical analogies with the detailed experimentation results, it is inferred that biped robots with rigid feet will have to suffer awkward and unstable walking gait, heavier and strenuous steps, and lower energy efficiency while walking. The paper concludes the necessity of bionic design of the robot feet for improving the walking quality of the biped robots. The conclusion and the experiment data will be of significant value for future work of robot design and evaluation.

Remote sensing satellite image de-noising is an important step in image preprocessing. Four de-noising algorithms for remote sensing images are investigated in this paper: BM3D, DCT, K-SVD, and wavelet threshold method. A modified method based on K-SVD is also proposed. The basic principles of the four kinds of de-noising methods are introduced, and the modified method is analyzed thoroughly. In the improved method, high-frequency information is extracted through High-pass filtering, and then sparse representation and reconstruction are carried out to maintain the detail information. Comparative experiments are conducted to reveal the advantages and disadvantages of each method in satellite images de-noising, and the results demonstrate that the proposed method can get better de-noising result as well as keeping the details at the same time.

This paper presents an improved semi-global matching algorithm which is robust to the different radiometric conditions. Firstly, Census transform instead of mutual information is adopted to calculate the matching cost because of its robustness to radiometric changes. Then, an additional self-adaptive matching penalty is added into the cost aggregation along every accumulation path of semi-global matching to preserve depth continuities. Finally, the winner-take-all strategy is applied to calculate the optimal disparity value and a few post-processing methods are performed to refine the disparity image. Experiments on Middlebury datasets reveal that the proposed method can always perform better than the SGM, GF and ELAS algorithms under different radiometric conditions, and it can also be used in the real-world scene successfully.

Objective To study the influence of hepatocyte growth factor (HGF) antibody on the lung expression level of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods Thirty male Wistar rats were randomly divided into 3 groups: control group, model group, and intervention group. Endotoxin was intratracheally infused in the model and intervention groups. HGF antibody was injected in the rats of the intervention group from day 1 to day 14, while the same volume of saline was injected in the control group. The rats were sacrificed on day 28 after endotoxin treatment. The amounts of MMP-9 mRNA and TIMP-1 mRNA were measured by reverse transcription-polymerase chain reaction, and protein expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry. Results In the model group, both mRNA and protein expression levels of TIMP-1 were significantly increased, the same as MMP-9. In the intervention group, the increase of TIMP-1 was remarkably reduced compared with the model group, while the mRNA and protein expression levels of MMP-9 were still increased. Conclusion HGF activity may accelerate the repair of lung injury through contrary regulating the expression levels of TIMP-1 and MMP-9.

Rationale:Methamphetamine (METH) abuse is increasing rapidly all over the world and becoming a significant public health concern in China. However, abdominal complications secondary to METH abuse are usually overlooked. We describe an unusual case of gangrenous cholecystitis and small intest

The frequent attacks on network infrastructure, using various forms of denial of service attacks, have led to an increased need for developing new techniques for analyzing network traffic. If efficient analysis tools were available, it could become possible to detect the attacks and to take action to weaken those attacks appropriately before they have had time to propagate across the network. In this paper, we propose an SNMP MIB oriented approach for detecting attacks, which is based on two-tier GCT by analyzing causal relationship between attacking variable at the attacker and abnormal variable at the target. According to the abnormal behavior at the target, GCT is executed initially to determine preliminary attacking variable, which has whole causality with abnormal variable in network behavior. Depending on behavior feature extracted from abnormal behavior, we can recognize attacking variable by using GCT again, which has local causality with abnormal variable in local behavior. Proactive detecting rules can be constructed with the causality between attacking variable and abnormal variable, which can be used to give alarms in network management system. The results of experiment showed that the approach with two-tier GCT was proved to detect attacks early, with which attack propagation could be slowed through early detection.

The behaviors of two kinds of cymbal piezoelectric-metal composite membrane for piezoelectric synthetic jet actuator (PSJA) are investigated to improve the driving capability of PSJA. The FEM models of piezoelectric-metal composite membranes are established and solved using ANSYS software. Two dimensionless geometry characteristic parameters of membrane, δ1 and δ 2, are defined and used to analyze the influences of geometry on the driving capability of membrane. Cymbal and plane membrane specimens are manufactured and tested to verify the results of simulation. The results of research show that there is an optimal combination between δ1 and δ 2 that improve effectively the deformation and driving capability of PSJA membrane, especially the half cymbal membranes can provide the maximum deformation and driving capability under the same input and boundary condition. δ 1 = 0.5, δ2 = 1.2 is a good combination for half cymbal membrane in the proposed research.

Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats.