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In robot visual servoing system, effective detected the region of interest area (ROI) in target images is the first problem should be solved, but the detection is susceptible to an unstructured environment. In this paper, an instance segmentation network algorithm based on Mask Region Convolutional Neural Networks (Mask R-CNN) framework is proposed for ROI image preprocessing. As instance segmentation technology can distinguish complex environmental information, so first with this advantage filter out message such as shape or similar area to target image, then with semantic segmentation technology add special category labels to the filtered images and distinguish different individual instances in similar categories. Finally through the series steps aforementioned, robot vision system can overcome the impact of environmental factors and identify the target image. The proposed method is used to detect target image under five constraints such as occlusion and reflection, result shows the algorithm can effectively deal with challenges that brought by complex constraints, and even can predict the location data of missing information based on some image information. In addition, based on the algorithm proposed in this paper, we used one seven axis robot visual servo platform, executed visual servoing experiment under different unstructured environments, further verifies the effectiveness of our proposed method.

Extracting genes involved in cancer lesions from gene expression data is critical for cancer research and drug development. the method of feature selection has attracted much attention in the field of bioinformatics. Principal Component Analysis (PCA) is a widely used method for learning low-dimensional representation. Some variants of PCA have been proposed to improve the robustness and sparsity of the algorithm. However, the existing methods ignore the high-order relationships between data. In this paper, a new model named Robust Principal Component Analysis via Hypergraph Regularization (HRPCA) is proposed. In detail, HRPCA utilizes L2,1-norm to reduce the effect of outliers and make data sufficiently row-sparse. And the Hypergraph Regularization is introduced to consider the complex relationship between data. Important information hidden in the data are mined, and this method ensures the accuracy of the resulting data relationship information. Extensive experiments on multi-view biological data demonstrate that the feasible and effective of the proposed approach.

Cronobacter species are a group of Gram-negative opportunistic pathogens, which cause meningitis, septicemia, and necrotizing enterocolitis in neonates and infants, with neurological sequelae in severe cases. Interest in Cronobacter has increased significantly in recent years due to its high virulence in children. In this review, we summarize the current understanding of the prevalence of Cronobacter species in several important food types. We discuss the response mechanisms enabling persistence in adverse growth conditions, as well as its pathogenicity. We emphasize the food safety concerns caused by Cronobacter and subsequent control methods, and clinical treatments.

The exploration of single cell RNA-sequencing (scRNA-seq) technology generates a new perspective to analyze biological problems. One of the major applications of scRNA-seq data is to discover subtypes of cells by cell clustering. Nevertheless, it is challengeable for traditional methods to handle scRNA-seq data with high level of technical noise and notorious dropouts. To better analyze single cell data, a novel scRNA-seq data analysis model called Maximum correntropy criterion based Non-negative and Low Rank Representation (MccNLRR) is introduced. Specifically, the maximum correntropy criterion, as an effective loss function, is more robust to the high noise and large outliers existed in the data. Moreover, the low rank representation is proven to be a powerful tool for capturing the global and local structures of data. Therefore, some important information, such as the similarity of cells in the subspace, is also extracted by it. Then, an iterative algorithm on the basis of the half-quadratic optimization and alternating direction method is developed to settle the complex optimization problem. Before the experiment, we also analyze the convergence and robustness of MccNLRR. At last, the results of cell clustering, visualization analysis, and gene markers selection on scRNA-seq data reveal that MccNLRR method can distinguish cell subtypes accurately and robustly.

Despite the advantages of scalability and flexibility, Security Function Virtualization (SFV) raises concerns about its own security. To enhance the security of SFV, a promising approach is to run critical components of off-the-shelf security software inside SGX enclaves. This idea, however, is hardly practical due to the difficulty of detaching components from the monolithic security function and the unacceptable cost of running them in enclaves. In this work, we propose S-Blocks, an architecture to modularize a virtual security function (VSF) and protect its key modules with SGX in an efficient manner. Through systematically decomposing modules of a VSF into related elements, it is easy to put the key modules and elements of the VSF into an enclave. Furthermore, aiming at addressing state consistency and secure migration issues of security function scaling, we design a fine-grained state synchronization and migration mechanism to ensure lose-free, order-preserving, and state security for VSFs. To demonstrate the effectiveness of our approach, we prototype S-Blocks using Fast-Click on a real Skylake platform and implement three main types of virtual security functions based on the S-Blocks architecture. Our evaluation results show that S-Blocks only imposes a manageable performance overhead, and low latency and resource consumption when protecting VSFs.

BACKGROUND Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure. OBJECTIVES To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE. METHODS In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n = 13) or conventional (n = 14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not. RESULTS During the intervention period, total UPRE was 91% lower with organic (mean 17 μg/d; 95% CI: 15, 19) than with conventional (mean 180 μg/d; 95% CI: 153, 208) food consumption (P

Traditional classification learning algorithms have several limitations: 1) they are time consuming for the large-scale training multivariate time-series (MTS) data, and unsuitable for the dynamically added training data; 2) as the number of the training MTS data becomes larger, they could not achieve the desired classification accuracy; 3) most of them do not consider how to make use of the unlabeled samples to enhance the classifier performance; and 4) due to the high dimension of MTS and complex relationship among variables, existing online learning algorithms are not effective to update shapelet-based association rules. Up to now, few work touched online classification learning for dynamically added unlabeled examples. To efficiently address these issues, we propose an online rule-based classifier learning framework on dynamically added unlabeled MTS data (ORCL-U). This framework integrates a confidence-based labeling strategy (CLS) and an online rule-based classifier learning approach (ORBCL). Extensive experiments on ten datasets show the effectiveness and efficiency of our proposed approach.

The SARS-CoV-2 pandemic spread worldwide unabated. However, achieving protection from the virus in the whole respiratory tract, avoiding blood dissemination, and calming the subsequent cytokine storm remains a major challenge. Here, we develop an inhaled microfluidic microsphere using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from angiotensin-converting enzyme II (ACE2) receptor-overexpressing cells and macrophages. By timely competing with the virus for ACE2 binding, the inhaled microspheres significantly reduce SARS-CoV-2 infective effectiveness over the whole course of the respiratory system in vitro and in vivo. Moreover, the inhaled microspheres efficiently neutralize proinflammatory cytokines, cause an alternative landscape of lung-infiltrated immune cells, and alleviate hyperinflammation of lymph nodes and spleen. In an acute pneumonia model, the inhaled microspheres show significant therapeutic efficacy by regulation of the multisystem inflammatory syndrome and reduce acute mortality, suggesting a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration., Graphical abstract, Progress and potential The SARS-CoV-2 pandemic spread worldwide unabated. Protection of the whole course of the respiratory airway remains a major challenge. In this work, inhaled microfluidic methacrylate hyaluronic acid hydrogel microspheres (termed iAE-PMS) have been genetically engineered with ACE2 membranes and proinflammatory macrophages for competing viruses and cytokine binding. The iAE-PMS with wide distribution enables deposition throughout the respiratory system, providing protection for not only the lung but also the upper respiratory tract and nasopharynx. Furthermore, iAE-PMS presents clearance by the swinging of the cilia and enzymatic hydrolysis. The microspheres captured by cilia effectively reduce the virus output from the infected person to the environment. The respiratory-confined degradation significantly avoids systemic viral spreading. This inhaled microsphere is proposed as a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration., Inspired by SARS-CoV-2 infecting alveolar epithelial cells through ACE2 receptors, an inhaled modular microfluidic microsphere aerosol was developed using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from ACE2 receptor-overexpressing cells and proinflammatory macrophages to capture the virus over the whole course of the respiratory tract before viremia occurs.

The progression of breast cancer is closely related to obstructive sleep apnea-hypopnea syndrome (OSAHS). Low concentrations of cannabinoids promote tumor proliferation. However, the role of cannabinoid receptors (CBs) in chronic intermittent hypoxia (CIH)-induced breast cancer has not been reported. The migration and invasion of breast cancer cell lines (MCF-7 and T47D) were measured by scratch assay and transwell assay. Gene and protein expressions were analyzed by qPCR and western blotting. Tumor xenograft mice model were established to evaluate the function of CBs. We observed that chronic hypoxia (CH) and CIH increased CBs expression and promoted migration and invasion in breast cancer. Mice grafted with MCF-7 exhibited obvious tumor growth, angiogenesis, and lung metastasis in CIH compared with CH and control. In addition, CIH induced CBs expression, which subsequently activated insulin-like growth factor-1 receptor (IGF-1R)/AKT/glycogen synthase kinase-3β (GSK-3β) axis. Knockdown of CBs alleviated CIH-induced migration and invasion of breast cancer in vitro. Furthermore, CIH exaggerated the malignancy of breast cancer and silencing of CBs suppressed tumor growth and metastasis in vivo. Our study contributed to understanding the role of CIH in breast cancer development modulation., Graphical abstract, The role of CBs in CIH-induced breast cancer remains unknown. In this study, we found that CIH induced CBs expression via activating IGF-1R/AKT/GSK-3β signaling. CBs knockdown inhibited CIH-induced progression of breast cancer. Our study revealed that CBs might be a new therapeutic strategy for breast cancer.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been shown to be an effective, reliable and practical clinical nursing method to support operations on a range of physiological systems, but its effects on robotic radical prostatectomy (RRP) are still unclear. This study assesses the clinical effects of ERAS in RRP. METHODS: Various databases including PubMed, EMBASE, Web of Science and China National Knowledge were searched for relevant studies, in particular full-text articles comparing ERAS groups and conventional groups for RRP. All included articles were subject to a quality assessment, and the data analysis was conducted with Review Manager (5.3). Forest plots, sensitivity analyses, and bias analyses were also prepared based on the included articles. RESULTS: In total, 8 studies were identified that met the inclusion criteria. The results showed that ERAS groups exhibited significantly reduced time of flatus [mean difference (MD) =−0.58; 95% confidence interval (CI): −0.88, −0.29; P=0.0001], time of catheter removal (MD =−1.65; 95% CI: −2.15, −1.16; P

Aims The objective of this study is to explore and compare the strength of associations between work-related potential traumatic events and burnout among operating room nurses based on three different approaches. Design The study followed a multisite cross-sectional design. Methods A stratified sampling method was conducted. Cities in the Shandong Province were divided into four groups, and two tertiary hospitals were randomly selected from all tertiary hospitals in cities of each group. A total of 361 eligible operating room nurses provided valid questionnaires between June and November 2019. Work-related potential traumatic events questionnaire and the Chinese version of the Maslach Burnout Inventory were conducted. Associations between individual, cumulative potential traumatic events, as well as latent class analysis-derived patterns of potential traumatic experiences with burnout were examined using logistic regression analysis. Results Specific traumatic events (e.g., patients' sudden death, bullying and ostracism from colleagues) were independently associated with an increased risk of burnout. Work-related potential traumatic events had a cumulative effect on burnout, whereby operating room nurses exposed to cumulative potential traumatic events carried a higher risk for burnout than others. The "multiple work-related potential traumatic events" pattern derived by latent class analysis was related to an increased risk of high depersonalization. Conclusion Operating room nurses who reported specific or multiple work-related potential traumatic events were at high risk for burnout. It is of great significance to provide qualified and timely counselling or support. Impact This study is the first to focus on work-related potential traumatic events among operating room nurses and examine their relationship with burnout based on three perspectives. The findings could help identify those operating room nurses who are at high risk of burnout in clinical practice. Hospital managers should develop targeted interventions to prevent or mitigate the harmful impact of potential traumatic events on occupational health.

Background The pandemic of COVID‐19 has a persistent impact on global health, yet its sequelae need to be addressed at a wide scale around the globe. This study aims to investigate the characteristics, prevalence, and risk factors for mid‐term (>6 months) clinical sequelae in a cohort of COVID‐19 survivors. Methods Totally 715 COVID‐19 survivors discharged before April 1, 2020, from three medical centers in Wuhan, China, were included. The longitudinal study was conducted by telephone interviews based on a questionnaire including the clinical sequelae of general, respiratory, and cardiovascular systems. Demographics and some characteristics of clinical sequelae of the survivors were recorded and analyzed. Multivariate logistic regression analysis was applied to explore the risk factors for the sequelae. Results The median time interval from discharge to telephone interview was 225.0 days. The COVID‐19 survivors' median ages were 69 years, and 51.3% were male. Among them, 29.9% had at least one clinical sequela. There were 19.2%, 22.7%, and 5.0% of the survivors reporting fatigue, respiratory symptoms, and cardiovascular symptoms, respectively. Comorbidities, disease severity, the application of mechanical ventilation and high‐flow oxygen therapy, and the history of re‐admission were associated with the presence of clinical sequelae. Conclusions Our study provides further evidence for the prevalence and characteristics of clinical sequelae of COVID‐19 survivors, suggesting long‐term monitoring and management is needed for their full recovery.

Purpose The aim of this study was to assess the effect of high-quality nursing based on the concept of childlike interest in children with cleft lip and palate following operation on healing time, degree of pain, psychological state, quality of life, and the occurrence of complications. Methods A series of 62 children with cleft lip and palate was treated in our hospital from January 2019 to March 2021. The patients were randomly divided into observation group (31 cases, given high-quality nursing based on childlike interest) and control group (31 cases, given routine nursing intervention). The healing time and hospital stay of the two groups were recorded. The degree of pain, psychological state and quality of life of the two groups before and after intervention were compared, and the occurrence of complications was closely monitored. Results Compared with the control group, the healing time and hospital stay of the study group were significantly shorter after the intervention (P 0.05), while after intervention the SDS and SAS scores of the two groups were lower than those before treatment. Compared with the control group, the SDS and SAS scores of the study group were remarkably lower (P 0.05), while after the intervention, the scores of quality of life in the two groups were associated with lower outcomes. Compared with the control group, the scores of quality of life in the study group were significant lower (P Conclusions High quality nursing based on childlike interest exerted beneficial outcomes in terms of shortening the healing time and hospital stay, reducing the degree of pain and complications, as well as improving the psychological state and quality of life of children harboring cleft lip and palate. Additionally, its high safety feature contributes to the wide application for clinical practice.

Cuie Gao,1 Lan Ge,1 Dewei Chen,2 Mengjie Zhang,2 Li Zhao,2 Wenying Liu,1 Shuguang Chen,1 Juan Wang,1 Cunjian Zhou,1 Xingwang Zhao,1 Shifei Li,1 Zhiqiang Song,1 Jian Li1 1Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Department of Pathophysiology, Army Medical University, Chongqing, 400038, People’s Republic of ChinaCorrespondence: Jian Li; Zhiqiang SongDepartment of Dermatology, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of ChinaTel +86 23 68754290Fax +86 23 68755290Email leejian860@126.com; drsongzq@hotmail.comPurpose: Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment.Patients and Methods: We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea, while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of C–C chemokine receptor 2 (CCR2) on monocytes and plasma levels of CC-chemokine ligand 2 (CCL2), high mobility group box-1 (HMGB-1), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were measured in HC and rosacea patients before and after treatment.Results: The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythematotelangiectatic rosacea (ETR) and ETR-papulopustular rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phymatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1β and TNF-α in patients than in HC, which all significantly decreased after treatment.Conclusion: Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea.Keywords: monocytes, classical monocytes, CCR2, rosacea

Pancreatic cancer, with high morbidity and mortality rates, is one of the most malignant tumors worldwide. Despite extensive research, the prognosis remains poor. Autophagy, a lysosomal-mediated, highly conserved degradation process that removes abnormal proteins and damaged organelles from the body, is upregulated in pancreatic ductal adenocarcinoma. Based on differences in the tumor microenvironment and tumor stage, the functions of autophagy in the pathophysiology and treatment of pancreatic cancer differ. In the initial phase, autophagy inhibits the transformation of precancerous lesions to cancer. However, in the progressive stage, autophagy promotes tumor growth. Autophagy is also one of the main mechanisms of drug resistance during treatment. Here, we describe the role of autophagy in pancreatic cancer progression and discuss relevant treatment strategies for this disease.

Non-negative matrix factorization (NMF) is a dimensionality reduction technique based on high-dimensional mapping. It can effectively learn part-based representations. In this paper, we propose a method called Dual Hyper-graph Regularized Supervised Non-negative Matrix Factorization (HSNMF). To encode the geometric information of the data, the hyper-graph is introduced into the model as a regularization term. The advantage of hyper-graph learning is to find higher order data relationship to enhance data relevance. This method constructs the data hyper-graph and the feature hyper-graph to find the data manifold and the feature manifold simultaneously. The application of hyper-graph theory in cancer datasets can effectively find pathogenic genes. The discrimination information is further introduced into the objective function to obtain more information about the data. Supervised learning with label information greatly improves the classification effect. Furthermore, the real datasets of cancer usually contain sparse noise, so the -norm is applied to enhance the robustness of HSNMF algorithm. Experiments under The Cancer Genome Atlas (TCGA) datasets verify the feasibility of the HSNMF method.

Background Although open reduction and internal fixation (ORIF) is recommended for lateral condylar humerus fractures (LCHFs) displaced by > 4 mm, several studies have reported the use of closed reduction and percutaneous pinning (CRPP) to treat LCHFs with significant displacement. However, little is known about the clinical differences between these two surgical techniques. This study aimed to compare the therapeutic effects of CRPP and ORIF in treating LCHFs displaced by > 4 mm. Methods We retrospectively reviewed pediatric LCHFs displaced by > 4 mm treated with either CRPP or ORIF at our center from June 2019 to October 2020. Song and Milch fracture classifications were used. Variables such as age at injury, sex, side injured, fracture displacement, fracture type, operating time, postoperative treatment, and complications were compared between the two techniques. Results One hundred twenty LCHFs met inclusion criteria. There were 36 Milch type I and 84 type II LCHFs, and 69 Song stage 4 and 51 stage 5 LCHFs. CRPP was performed in 45 cases and ORIF in 75 cases. No differences were found in age, sex, side injured, preoperative displacement, postoperative displacement, and length of immobilization between the CRPP and ORIF groups. There was a difference between operation time and pin duration. The CRPP group had shorter operation times and pin duration, and required no additional operations to remove internal pins. The average follow-up duration was 13.9 months. All patients achieved fracture union, and no complications such as infection, nonunion, delayed union, osteonecrosis, fishtail deformity, cubitus varus or valgus, or pain were recorded during follow-up. Bone spurs, lateral prominences, and decreased carrying angle were common complications in all groups. No obvious cubitus varus was observed. Unaesthetic scars were only observed in the ORIF groups. No differences in range of motion or elbow function was found among the different therapies. Conclusions Both CRPP and ORIF can achieve satisfactory clinical outcomes in treating LCHFs displaced by > 4 mm. No differences were found in complications or prognoses between the two groups. However, CRPP shows some advantages over ORIF, like less invasive surgery, no obvious scarring, and no need for secondary surgery with anesthesia for pin removal.

Soluble solids content (SSC) is one of the important components for the assessment of fruit quality. Near-infrared (NIR) spectroscopy, multispectral and hyperspectral imaging techniques are widely used methods for the SSC estimation. However, the high prices are unaffordable for small commercial orchards. The objective of this work is to present a computer vision system for the SSC estimation of “Fuji” apples in different ripening stages. Multiple information of the color channels (channel a* and channel b*) in L*a*b* color space translated from RGB images were applied to extract color features. Stacked autoencoder (SAE) algorithm was used to extract color features in pixel-level, and the trained parameters were used as the initial parameters of the prediction model by using back propagation neural network (BPNN) algorithm. The results show that the prediction accuracy of the SAE-BPNN model based on color features in pixel-level is higher than that of the BPNN model based on pure color features in feature-level. Moreover, the model with fusion information of both color channels as inputs can get better prediction results than that of single channel. The SAE-BPNN model with SAE structure of 270-120-30 yielded the best result with R p 2 = 0.5953 and RMSEP = 0.8856%. This research indicates that RGB imaging technology based on multiple information has potential for the SSC prediction, which provides reference values for fruit harvesting and non-destructive evaluation of fruit quality.

Extreme learning machine (ELM) has fast learning speed and perfect performance, at the same time, ELM provides a unified learning framework with a widespread type of feature mappings which can be applied in multiclass classification applications directly. These advantages make ELM become one of the best classification algorithms, and ELM has attracted great attention in supervised learning and semi-supervised learning. However, noise and outliers of data are usually existed in the real world, which will affect the performance of ELM. To improve the robustness and classification performance of ELM, we propose the Kernel Risk-Sensitive Mean p-power Loss Based Hyper-graph Regularized Robust Extreme Learning Machine (KRP-HRELM) method. On the one side, as a nonlinear similarity measure defined in the reproducing kernel space, the kernel risk-sensitive mean p-power loss (KRP) can effectively weaken the negative effects caused by noise and outliers. Therefore, the KRP is introduced into ELM to enhance its robustness. Then, the application of hyper-graph can help the ELM to explore higher-order geometric structures among more sampling points, thereby obtaining more comprehensive data information. In addition, to obtain a more sparsity network model, the L2,1-norm is used to constrain the output weight. On the other side, improving the practical application ability of KRP-HRELM is also the focus of our research, so KRP-HRELM is extended to semi-supervised learning, which is called the semi-supervised KRP-HRELM (SS-KRP-HRELM). Notably, the results of the robustness experiment have proved that our method has extraordinary robustness. At the same time, by using four evaluation measures such as accuracy, recall, precision, and F1-measure, to evaluate the classification results, we can find that our method has obtained better classification performance than other advanced methods.

Objective Diabetes increases the risk for cancers. However, whether it is associated with hematologic malignancies is not clear. The present study investigated the association between diabetes and acute lymphocytic leukemia (ALL), acute myeloid leukemia (ML), non-Hopkin lymphoma (NHL), and multiple myeloma (MM). Methods Newly diagnosed adult cancer patients were recruited consecutively from our clinical database. Peoples from a local enterprise were recruited to create a small-scale population-based dataset. We compared the diabetes prevalence between the cancer patients and the local people; an increase in diabetes prevalence in the cancer patients suggests an association between diabetes and the cancer(s). Results We found that the prevalence of diabetes was 19.7%, 21.3%, 12.5%, and 12.0% in ALL, AML, NHL, and MM, respectively, which was higher than that (9.1%) in the local people. Despite that there were more male than female cancer patients, there were more female than male diabetic patients. The increase in diabetes prevalence occurred in ALL and NHL patients aged 18 to 39 years old as well as in AML patients over 40. In MM patients, the increase in diabetes prevalence (18.6%) occurred only in females. Approximately 70% of the diabetic patients were undiagnosed before the diagnosis of the blood cancer. Approximately half of the pre-existing diabetic patients had anti-diabetic treatment, with over 70% of them still had poor glycemic control. Conclusions Our results suggest that diabetes is associated with ALL, AML, NHL, and MM, at least in adult patients.

The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation. A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5). Among 1046 patients with PRiS

Introduction CCAs are dense and desmoplastic tumors with an abundant tumor microenviroment (TME). The evolving TME is characterized by reciprocal interactions between cancer cells and their environment and is essential in facilitating tumor progression. The TME has non-immune and immune components. Non-immune cell types include cancer-associated fibroblasts (CAFs) and endothelial cells accompanying tumor angiogenesis. Immune cell types include elements of the innate and adaptive immune response, and can have pro-tumor or anti-tumor roles. The TME can shape treatment response and resistance. Therefore, elements of the TME are attractive therapeutic targets. TME targeting therapies have been evaluated in preclinical and clinical studies but only a small subset of patients has a meaningful response. Areas covered We discuss the TME components and potential TME targeting strategies. Literature search was performed on PubMed and clinicaltrials.gov up until October 2021. Expert opinion Elucidating the CCA TME is essential for developing effective treatment strategies. Preclinical models that recapitulate the disease [such as organoids] are important tools in uncovering the intricate crosstalk in the CCA TME. Characterization of patient-derived specimens using multi-omic and single-omic technologies can dissect the cellular interplay in the CCA TME which can guide development of effective treatment strategies and identify biomarkers for patient stratification.

Trust has played a pivotal role in the evolution of modern human societies, and it continues to be an essential underpinning of our social interactions. It is therefore important that we develop rigorous mathematical foundations that will enable us to better understand what promotes and what erodes trust and how to best preserve trustworthiness. To that effect we propose a trust game, wherein investors, trustworthy trustees, and untrustworthy trustees compete for assets subject to a third-party evaluation system that oversees and modifies each individual reputation. We use Monte Carlo simulations on social networks to determine critical values of the degree of rationality and the reputation threshold that warrant high levels of trust and social wealth. We show that if investors have access to the reputation scores of trustees, the fraction of untrustworthy trustees drops if only the degree of rationality is sufficiently large, and this irrespective of reputation threshold that determines the cutoff for untrustworthiness. But even though investors are allowed irrational investments, trust can still proliferate if the reputation threshold is sufficiently high. Our results thus formalize essential mechanisms of trust in social networks, which also outline policies to diminish untrustworthiness that can be employed in real life.

Background Although the concentrations of progesterone (P4) and 17-hydroxyprogesterone (17-OHP) have been correlated with some characteristics of metabolic syndrome (MetS), the relationships with MetS are inconclusive. Therefore, we investigated the relationship between P4 and 17-OHP with MetS. Methods In all, the present study includes 4807 participants. Serum P4 and 17-OHP were measured through liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent and combined effects of P4 and 17-OHP on MetS. Results After adjusting for multiple variables, the positive association of P4 with MetS was observed in postmenopausal women (Third tertiles vs First tertiles: OR = 1.49, 95% CI: 1.20–1.86) and the negative association of 17-OHP with MetS was observed in men (Third tertiles vs First tertiles: OR = 0.43, 95% CI: 0.32–0.58). Compared with the combination of low P4 and low 17-OHP, the combination of high P4 and high 17-OHP were significantly related to MetS in postmenopausal women (OR = 1.71, 95% CI: 1.18–2.48). Moreover, the combination of low P4 and high 17-OHP was negatively associated with MetS in men (OR = 0.41, 95% CI: 0.24–0.69). Conclusion The association between P4 and MetS in postmenopausal women was positive, whereas 17-OHP was negatively associated with MetS in men. Additionally, their combination has a synergistic effect on MetS in postmenopausal women and an antagonistic effect on MetS in men.

The aim of our study was to investigate the genetic characteristics in patients with familial or young-onset amyotrophic lateral sclerosis (ALS) in a Chinese center.Patients with familial or young-onset (age of onset 45 years old) ALS were reviewed. The clinical data was collected. Whole-exome sequencing was performed to identify the disease-associated variants. Single-nucleotide variants and small insertions/deletions were further predicted with silico tools and compared to the Single Nucleotide Polymorphism Database, Exome Aggregation Consortium, and the 1000 Genomes Project. The evolutionary conservations were estimated, and the structures of proteins were constructed by Swiss-Model server. Immunohistochemistry was used to confirm the misfolded SOD1 protein.Three familial ALS and 5 young-onset ALS were enrolled. Genetic analysis identified related variants of SOD1 (4/6, 66.7%), FUS (1/6, 16.7%), and NEK1 (1/6, 16.7%) in 6 patients. Three of them were familial probands (3/3, 100%), and the others were sporadic young-onset patients (3/5, 60%). NEK1 c.290G A mutation (NM_012224.2 exon4) in a patient with familial ALS and SOD1 c.362A G mutation (NM_000454 exon5) in a young-onset ALS patient were novel. The novel mutations were predicted to be deleterious, affected evolutionarily highly conserved amino acid residue and the formation of hydrogen bonds between the mutated site and its surrounding amino acid residues. Misfolded SOD1 protein was identified in patient with SOD1 c.362A G mutation.Two novel mutations were detected in our patients. Patients with familial or young-onset ALS often carried related gene mutations, and genetic sequencing should be thus routinely performed.

Introduction/aims Patients with acute motor axonal neuropathy (AMAN) generally have pure motor neuropathy and clinicians usually do not link pain with AMAN. The aim of this retrospective study was to describe the character, location, and intensity of pain in AMAN and acute inflammatory demyelinating polyneuropathy (AIDP) in the acute phase. Methods This was a retrospective study in 44 patients with Guillain-Barre syndrome (GBS) having progressive weakness of more than one limb. The information, including the demographic characteristics, preceding infections, clinical symptoms and signs, severity at nadir, the characteristics of pain, use of analgesics, laboratory and electrophysiological data, and the medical treatment for GBS, were collected from the medical records. Results In 44 patients, 40.9% were diagnosed as AMAN, and 34.1% as AIDP. Pain was more prevalent in AMAN (76.5%) than in AIDP (26.7%, P = .02). Low back and extremities were the most common locations of pain in AMAN (7/13 and 7/13, respectively) and AIDP (2/4 and 2/4, respectively). Discussion Pain was a common symptom in AMAN in the acute stage. The presence or absence of pain is not useful for distinguishing AIDP from AMAN.

Background. Gastrointestinal motility disorder is a common gastrointestinal disease, which seriously affects life quality. Traditional Chinese medicine (TCM) has been widely used as an alternative therapy for gastrointestinal motility disorder. Acacetin is a natural flavonoid compound that has antioxidant and anti-inflammatory, antidepressant, and anticancer properties. However, the efficacy of Acacetin in the treatment of gastrointestinal motility disorders has not been studied. Our aim was to investigate the mechanism of Acacetin-alleviated gastrointestinal motility disorder and its efficacy based on network pharmacology. Methods. We performed network pharmacology to predict the active components, match Weishu decoction (WSD) targets in gastrointestinal motility disorders, and investigate its potential pharmacological mechanisms. We performed the GO and KEGG enrichment analysis. In vivo, we investigated the effects of Acacetin in the gastrointestinal motility disorder model. Results. Based on network pharmacological method, the key active ingredient of WSD was identified as Acacetin, and the enrichment signaling pathway was the PI3K-AKT signaling pathway. Acacetin and Mosapride accelerated gastric emptying time, reduced gastric remnant rate, and increased small intestinal propulsion rate. The levels of GAS and MTL were increased after using Acacetin. These results indicated that Acacetin could improve gastrointestinal motility disorders. Among them, high-dose Acacetin showed a better effect. Acacetin could regulate protein and lipid metabolism in mice with gastrointestinal motility disorder. Furthermore, Acacetin could modulate gastrointestinal inflammation and apoptosis. The detection of the PI3K-AKT signaling pathway-related proteins showed that Acacetin improved gastrointestinal motility disorder by inhibiting the activation of the PI3K-AKT signaling pathway. Conclusion. The key ingredient Acacetin in WSD could alleviate gastrointestinal motility disorder by inhibiting the activation of the PI3K-AKT signaling pathway based on network pharmacology analysis. The efficacy and safety of Acacetin treatment provide strong experimental support for the clinical treatment of gastrointestinal motility disorder.

Computer-assisted Collaborative Learning (CCL) is a good teaching technique to enhance students' learning and intellectual performance consistency. Several studies have been undertaken to recognize variables that affect student intellectual ability. Observation obtained from the studies helped students in the right way and improved their habits and personal condition in learning and intellectual performance. In this paper, the proposed method has a multi-level multi-class classification algorithm. The dataset is transformed into various problem syntheses, and adaptive methods such as Binary Significance (BS), Label Powerset (LP), Classifier Series (CS), K-Nearest Neighbor (KNN), and Machine Learning integrated K-Nearest Neighbor (MLiKNN) adaptive classifier algorithm. Finally, the variables that significantly impact the student's success are identified, and recommendations for enhancing those factors are suggested to enhance the student's intellectual ability. The outcomes observed from the proposed classifier framework provide more recommended strategies to enhance students' learning environment and intellectual ability.

Purpose Previous clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest. Methods Asphyxia was induced by blocking the endotracheal tube in 120 adult Sprague–Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel–Haenszel stratified analysis were used to explore the associations among gender, intervention and survival. Results The body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel–Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention. Conclusion In this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

Background Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids. Methods Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes. Results Testosterone was negatively related to periostin (ρ = −0.420, P = 0.009) and IL-5 (ρ = −0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage (ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males (ρ = 0.943, P = 0.005) but negative in females (ρ = −0.561, P = 0.030). Conclusions Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Objective: To evaluate the application of ultrasound (US) for the surgical intervention in patients with moderate and severe secondary hyperparathyroidism (SHPT), and to identify the risk of prolonged hypocalcemia after parathyroidectomy (PTX). Methods: A consecutive series of moderate and severe SHPT patients (n = 64) underwent ultrasound evaluation of parathyroid glands. Among the 64 patients who received 6-month medication therapies, ten patients with parathyroid hormone (PTH) 300~500 pg/mL were excluded from the study while 32 patients unresponsive to medication therapy (PTH > 500 pg/mL) received surgical interventions and 22 patients with PTH < 300 pg/mL received medication treatment alone. The correlations between the number, location, volume, sonographic features of parathyroid glands (PTGs), laboratory examinations, the duration of dialysis and the surgical necessity were analyzed. Total parathyroidectomy with synchronous auto-transplantation (PTX + AT) was performed in the surgical group. In both the surgical and medication group, patients with hyper-vascularity of the PTGs dominated (≥50%) were classified as a hyper-vascular subgroup, and the others as a hypo-vascular subgroup. The differences of post-operative calcium (Ca2+) levels and the incidence of prolonged hypocalcemia between hyper- and hypo- vascular subgroups were assessed. Results: Sonographic evaluations revealed that the numbers of detectable PTGs were higher in the surgical group than that of the medication group (p < 0.05). The detection of supernumerary PTGs was higher in the surgical group than that in the medication group (13/121, 10.7% vs. 2/71, 2.8%, p < 0.05). Baseline PTH, >2 detectable PTGs, detection of supernumerary PTGs, patients with hyper-vascular, and the duration of dialysis were positively associated with the necessity of surgical intervention. For patients in the hyper-vascular subgroup, the serum Ca2+ level was lower than that in the hypo-vascularity subgroup (p < 0.01). Conclusion: Ultrasonic features can provide useful information for management of surgical intervention of SHPT and prediction of the risk of prolonged hypocalcemia after PXT.

Carsharing-facilitating neighbourhood is an emerging concept in urban development that combines carsharing, sustainable transportation-residential planning, and attractive housing to reduce private car use and improve neighbourhood quality. To investigate residents’ preferences for such neighbourhoods, a stated choice experiment was designed that systematically varied attributes of carsharing-facilitating neighbourhoods to elicit their utility for people with a particular socio-demographic profile. The survey was conducted among residents who currently live in densely populated urban areas in The Netherlands. In total, 610 valid responses were obtained for analysis. To derive the utility of carsharing-facilitating neighbourhoods of a particular profile, a mixed logit model was estimated. Results indicate that the utility of a carsharing-facilitating neighbourhood primarily depends on carsharing cost, required carsharing booking time, green space density, housing costs, housing type, housing size and housing building year. Besides, the utility varies with socio-demographic characteristics, such as age, household composition, net monthly income, work status and education level. The estimated results can help policymakers and real estate developers understand the contribution of particular factors to the utility of carsharing-facilitating neighbourhoods, and determine target groups to develop implementation strategies.

PURPOSE Exercise-induced hypoalgesia (EIH) is frequently documented in the literature. However, the underlying neural mechanism of this phenomenon remains unclear. Here, we explored the effects of different intensities of isometric exercise on pain perception with a randomized controlled design and investigated its neural mechanisms through tracing the dynamic changes of heat-evoked brain responses. METHODS Forty-eight participants were randomly assigned to one of the three groups with different exercise intensities (i.e., high, low, and control). Their subjective pain reports and brain responses elicited by heat stimuli before and after exercise were assessed. RESULTS We observed that: (1) the increased pressure pain thresholds and heat pain thresholds on the dorsal surface of the hand and the biceps brachii muscle of the exercised limb (closed to the contracting muscle), and the decreased pressure pain ratings at the indexed finger of the unexercised limb; (2) more reductions of pain sensitivity on both the biceps brachii muscle and the dorsal surface of the hand induced by the high-intensity isometric exercise than the low-intensity isometric exercise; (3) both the high-intensity and low-intensity isometric exercise induced the reduction of N2 amplitudes and N2-P2 peak-to-peak amplitudes, as well as the reduction of ERP magnitudes elicited by the heat stimuli on the exercised limb. CONCLUSIONS The hypoalgesic effects induced by the isometric exercise were not only localized to the moving part of the body, but also can be extended to the distal part of the body. The exercise intensities play a vital role in modulating these effects. The EIH could be related to the modulation of nociceptive information transmission via a spinal gating mechanism and also rely on a top-down descending pain inhibitory mechanism.

Objective: To investigate patient-specific radioprotection methods for people in close contact with cancer patients treated by 125I-seed implantation. Methods: The initial dose rates (Ḋ0) at distances of 30 and 100 ​cm from 80 patients who had undergone 125I-seed implantation were measured within 24 ​h of the procedure. The dose rate at t (Ḋt) and effective dose (E) were calculated according to the measured values of Ḋ0. The appropriate precaution times for general adult family members, spouses, coworkers, and children or pregnant women were determined, and the relationships between Ḋ0 and precaution time for different close-contact groups were derived by curve-fitting the corresponding data. Results: The mean Ḋ0 values of 80 patients at distances of 30 and 100 ​cm were (15.24 ​± ​11.25) μSv/h and (1.96 ​± ​2.63) μSv/h, respectively (P ​

“Immune normalization” has emerged as a new paradigm in immunotherapy, which is proposed in cancer patients instead of conventional “immune-enhancement” therapy. Immune normalization may also be implemented in cancer prevention of “sub-healthy” individuals. We established in vitro cultured mixed-natural killer (NKM) cells to achieve immune normalization. The in vitro cytotoxicity of NKM cells was tenfold higher than that of peripheral blood mononuclear cells (PBMCs). The cytotoxicity of NKM cells was negatively correlated with the proportion of T-helper cells (cluster of differentiation: CD3+CD4+ T), and positively correlated with the proportion of NK cells (especially CD56brightCD16bright NK cells). Then, we defined “sub-healthy individuals” after measuring Programmed cell death protein-1 (PD-1) expression in PBMCs from 95 donors aged > 50 years. Furthermore, we evaluated the potential clinical application of NKM-cell therapy in 11 patients with malignant lymphoma, one patient with pancreatic cancer, and four sub-healthy individuals. NKM-cell therapy elicited good tolerance and side-effects were not found. In sub-healthy individuals, the proportion of CD3+PD-1+ T cells and CD3+CD8+PD-1+ T cells was reduced significantly after NKM-cell treatment. We demonstrated that a new method using NKM cells was safe and efficacious as adjuvant treatment for cancer patients as well as therapy for sub-healthy individuals. Normalization of the peripheral immune system through NKM-cell therapy could expand its scope of application in different disorders.

This study reports on an exploratory investigation aimed to achieve consumer segments based upon data collected from food delivery app users. Food delivery app user segments were identified and dev...

Rapid and accurate monitoring of biodiversity is a major challenge in biodiversity conservation. Obtaining data using unmanned aerial vehicles (UAV) provides a new direction for biodiversity monito...

Both atrial fibrillation (AF) and diabetes mellitus (DM) are documented risk factors for stroke; however, whether glycemic control is associated with the prevalence of stroke remains unclear in patients with AF and DM. The purpose of this study was to investigate the association between glycemic control assessed by continuous glucose monitoring (CGM) and the risk of stroke.In total, 510 AF patients with DM from April 2013 to June 2017 were included. The subcutaneous sensor of CGM was inserted after hospital admission and lasted for 72 consecutive hours. Time in range (TIR), a novel metric derived from CGM, was defined as the time spent in the target range (3.9-10 mmol/L). A logistic regression model was constructed by regarding TIR as a categorical variable and a continuous variable, respectively.The mean age of the 510 enrolled patients was 69.8 years. Patients who had previously suffered from stroke had a markedly lower TIR than those without diagnosed stroke (55.1%±19.0% vs. 64.2%±15.1%, P0.001). Compared to patients with TIR ≤46%, the risk of stroke decreased significantly with increasing TIR quartiles: adjusted odds ratios (ORs) of 0.80 for TIR of 46-65%, 0.64 for TIR of 65-81%, and 0.59 for TIR of81% (all P0.001). Taking TIR as a continuous variable, the adjusted OR was 0.89 [95% confidence interval (CI): 0.82-0.95] per 10% increment in TIR.This study found that better TIR is independently associated with a decreased risk of stroke in patients with AF and DM.

Background and aims We aimed to evaluate the effects of serum testosterone, obesity and their interaction on blood pressure (BP) parameters and hypertension among Chinese rural adults. Methods A total of 6199 adults were recruited from the Henan Rural Cohort Study. Serum testosterone was measured by liquid chromatography-tandem mass spectrometry. Logistic regression and linear regression were used to evaluate the association between testosterone, hypertension and BP parameters (including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)). A generalized linear model was performed to identify the interactive effects of testosterone and obesity on hypertension. Results High levels of serum testosterone were associated with a lower prevalence of hypertension in males (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.53, 0.89). After stratification by obesity, observed associations were only found in non-obese males. Each one-unit increase in ln-testosterone was associated with a 1.23 mmHg decrease in SBP, 0.97 mmHg decrease in DBP, and 1.05 mmHg decrease in MAP among males. Moreover, interactive effects between testosterone and obesity on hypertension and BP parameters were found, indicating that protective effects of serum testosterone on hypertension and BP parameters were counteracted and accompanied by increased values of obesity-related indicators in males, and additional testosterone increased BP parameters and prevalence of hypertension at high levels of waist-to-hip ratio and waist-to-height ratio in females. Conclusions Elevated levels of serum testosterone were associated with decreased BP parameters and prevalent hypertension in males, and obesity modifying effects of serum testosterone on BP parameters and hypertension.

Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor's breast origin. However, their specificities still have room to improve. Many nonbreast tumors express cytokeratin 7 and estrogen receptor, and urothelial tumors frequently express GATA3. There is a practical need for a new breast lineage marker that is sensitive and specific. Wnt family member proteins play critical roles in embryo development, tissue homeostasis and tumor development through β-catenin dependent and independent pathways. The current study evaluated Wnt9b and GATA3 expression in 163 primary breast cancers, 63 metastatic breast cancers, and 525 nonbreast epithelial tumors. The positive rates of Wnt9b and GATA3 in primary breast cancer were both 98.7%. The positive rates in metastatic breast cancer were 87.3% for Wnt9b and 96.8% for GATA3. For nonbreast tumors, including 64 cases of urothelial carcinoma, Wnt9b was negative in all except salivary gland carcinomas. The study demonstrated that Wnt9b is a breast cancer marker with similar sensitivity as GATA3 but with greater specificity than GATA3 and may ultimately become a useful diagnostic tool in routine surgical pathology practice.

Microorganisms may persist in the root canal system after root canal therapy (RCT). The purpose of this study was to explore the metronidazole (MTR)- and chlorhexidine (CHX)-loaded hydrogels as the potential application in intracanal medicaments for root canal disinfection. Ultraviolet cross-linked hydrogels (gGels) were synthesized by GelMA solution and photoinitiator, which were loaded with MTR (MTR@gGels) and CHX (CHX@gGels). gGels, MTR@gGels and CHX@gGels were characterized by scanning electron microscopy. The antimicrobial activity against E. faecalis, S. mutans and P. intermedia was assessed. Meanwhile, the biocompatibility of human dental pulp stem cells (hDPSCs) was evaluated. DCT, CCK-8, CFU and live/dead-stained biofilm results showed that the viability of E. faecalis, S. mutans and P. intermedia was significantly reduced in MTR@gGels and CHX@gGels in vitro. CCK-8 results showed considerable biocompatibility with hDPSCs. The filling and clearance of gGels in root canals were demonstrated in vivo. Therefore, MTR- and CHX-loaded hydrogels may be a potential application in intracanal medicaments for root canal disinfection.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing (January 2, 2021). Since there are no targeted therapies for COVID-19, the current focus is the repurposing of drugs approved for other uses. In some clinical trials, antiviral drugs such as remdesivir (Grein et al., 2020), lopinavir/ritonavir (LPV/r) (Cao et al., 2020), chloroquine (Gao et al., 2020), hydroxychloroquine (Gautret et al., 2020), arbidol (Wang et al., 2020), and favipiravir (Cai et al., 2020b) have shown efficacy in COVID-19 patients. LPV/r combined with arbidol, which is the basic regimen in some regional hospitals in China including Zhejiiang Province, has shown antiviral effects in COVID-19 patients (Guo et al., 2020; Xu et al., 2020). A retrospective cohort study also reported that this combination therapy showed better efficacy than LPV/r alone for the treatment of COVID-19 patients (Deng et al., 2020).

Cardiac embolism is the leading etiology of ischemic strokes. There are arguments about the left-right propensity of cardioembolic strokes.This study aimed to reveal the relationship between the different aortic arch types and the location of large vessel occlusion (LVO) in cardioembolic stroke.We retrospectively identified all patients with acute ischemic stroke admitted to our comprehensive stroke center who had medium- to high-risk cardioembolicsources according to the TOAST classification.Only those with LVO and available images of the aortic arch were included. Patients were classified into 3 groups according to the aortic arch types: Type I (n = 44), Type II (n = 105), Type III (n = 36).The thrombus was divided into large thrombus or small thrombus based on the location of LVO.Overall, left-sided strokes (50.8%) were almost equal to right-sided (49.2%). There was a growing tendency for the percentage of left-sided infarcts with advancement of the aortic arch types either in the total cases or in the atrial fibrillation cases, with no statistical difference between the 3 aortic arch types.In type III aortic arch, left-sided strokes (69.0%) were twice than right-sided (31%) in large thrombus (P 0.05), while right-sided strokes (85.7%) were more common than left-sided (14.3%) in small thrombus (P 0.05).Conversely, in type Ⅰ and II aortic arches, left-sided strokes were more common than right-sided in small thrombus, while right-sided strokes were more common than left-sided in large thrombus (P 0.05). The left-right propensity of cardioembolic stroke is related to the proximity of clot lodging in different aortic arch types.

Both bench and bedside investigations have challenged the supportive role of Hedgehog (Hh) activity in the progression of colorectal cancers, thus raising a critical need to further deeply determine the contribution of Hh to the growth of colorectal cancer. Combining multiple complementary means, including in vitro and in vivo inflammatory colorectal cancer models, and pathological analysis of clinical colorectal cancer patients samples. We report that colorectal cancer cells hijack prostaglandin E2 (PGE2) to non-canonically promote Hh transcriptional factor Gli activity and Gli-dependent proliferation of colorectal cancer cells in a Smo-independent manner. Mechanistically, PGE2 activates c-Jun N-terminal kinase (JNK), which in turn enables Gli2 to evade ubiquitin-proteasomal degradation by phosphorylating Gli2 at Thr1546. This study not only presents evidence for understanding the contribution of Hh to colorectal cancers, but also provides a novel molecular portrait underlying how PGE2-activated JNK fine-tunes the evasion of Gli2 from ubiquitin-proteasomal degradation. Therefore, it proposes a rationale for the future evaluation of chemopreventive and selective therapeutic strategies for colorectal cancers by targeting PGE2-JNK-Gli signaling route.

High-throughput sequencing of single-cell gene expression reveals a complex mechanism of individual cell's heterogeneity in a population. An important purpose for analyzing single-cell RNA sequencing (scRNA-seq) data is to identify cell subtypes and functions by cell clustering. To deal with high levels of noise and cellular heterogeneity, we introduced a new single cell data analysis model called Adaptive Total-Variation Regularized Low-Rank Representation (ATV-LRR). In scRNA-seq data, ATV-LRR can reconstruct the low-rank subspace structure to learn the similarity of cells. The low-rank representation can not only segment multiple linear subspaces, but also extract important information. Moreover, adaptive total variation also can remove cell noise and preserve cell feature details by learning the gradient information of the data. At the same time, to analyze scRNA-seq data with unknown prior information, we introduced the maximum eigenvalue method into the ATV-LRR model to automatically identify cell populations. The final clustering results show that the ATV-LRR model can detect cell types more effectively and stably.

To investigate sexual function in Chinese women with polycystic ovary syndrome (PCOS) and to explore the correlation with clinical and biochemical characteristics. A cross-sectional study was designed in 1000 PCOS women, aged 18–45 years, via the Chinese version of Female Sexual Function Index (FSFI) evaluating sexual function, with additional questions possibly related to sexual life. Clinical and biochemical characteristics likely to affect sexual function were determined, including anthropometric indicators, serum levels of hormones, luteinizing hormone to follicle-stimulating hormone ratio (LH/FSH ratio), prolactin (PRL), total testosterone (TT), free androgen index (FAI), sex-hormone-binding globulin (SHBG), glucose, and lipid metabolism indicators. Nine hundred ten PCOS women participated in the study, 685 patients were included after screening, and 211 were suitable to detect correlations of clinical and biochemical characteristics with sex function parameters. The mean total FSFI score was 24.19 ± 2.8; 79.56% of the women were at risk of female sexual dysfunction (FSD). Women doing regular aerobic exercise and use of contraception had higher FSFI scores, while those with a desire to conceive and clinical signs of hyperandrogenism had lower FSFI scores. There were negative associations of FSFI scores with age and body fat distribution. No significant associations between FSFI scores and hormonal factors (surprisingly including SHBG) were found, except for total testosterone and satisfaction (OR = 0.976, p = 0.002). HOMA-IR was significantly related to reduced desire score (OR = 0.914, p = 0.004) and lubrication score (OR = 0.964, p = 0.044). PCOS was associated with a high risk of FSD (defined according to FSFI) in about 80% of the women in our study, and clinical characteristics play a more important role.