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To resolve the problem of ductile fracturing of beam flanges in traditional connections with concrete-filled steel tube columns using site-welded side plates, an alternative connection design requiring minimal site welding was designed and studied. An explicit analysis method, considering the fracture strain criterion developed by the stress triaxiality path, was adopted to study the seismic performance and fracture resistance of the proposed connection. The results of a verified finite-element model indicated that the steel beam flange in the connection never fractured. The connection exhibited a notably higher maximum bending moment and ductility than the traditional connection. The side plates in the proposed connection were tension-bending or compression-bending elements, unlike in the traditional connection. The failure modes, maximum bending moment, ductility and stress distribution of the side plates were compared and analysed parametrically. Based on the stress distribution of the side plates according to the finite-element results, a fitting formula related to the width and thickness of the side plates was obtained. A formula to calculate the flexural capacity was also developed according to the force model of the proposed connection. The calculations and finite-element results were in good agreement.

Objectives: This study was to investigate the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expressions of LINC00665, miR-148b-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western blotting was used to detect KLF5 expression. The expression patterns of LINC00665, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: LINC00665 expression was up-regulated in ovarian cancer cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of LINC00665 was mainly situated in the cytoplasm. Besides, miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, expressions of LINC00665 and miR-148b-3p, and expressions of miR-148b-3p and KLF5 were negatively correlated, while expressions of LINC00665 and KLF5 were positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of miR-148b-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: LINC00665 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.

Ports are major energy consumers and carbon emission producers. Developing integrated port energy systems (IPES) is the key to solve this problem. The energy forms in an IPES include electricity, hydrogen, heat and natural gas. Hydrogen can be generated from surplus renewable energies via water electrolysis, and thus power the previously oil-fueled equipment. Meanwhile, the remaining hydrogen can be converted to natural gas by the methanation reaction. By using fuel cells, gas turbine, hydrogen boiler and gas boiler, hydrogen and natural gas can supply the electrical and heat loads in the port area, forming a closed-loop of energy flow. Based on the above energy coupling structure, a day-ahead optimal economic dispatching model for IPES is established. The model takes the energy conversion loss and carbon dioxide emissions into account. The second order conic relaxation is used to deal with the nonlinear part of power flow calculation. The linearization model for connecting heat source and heat load is built. Numerical results demonstrate that the proposed economic dispatching model effectively reduces the total energy cost and carbon dioxide emissions of IPES.

This research discussed a deep learning method based on an improved generative adversarial network to segment the hippocampus. Different convolutional configurations were proposed to capture information obtained by a segmentation network. In addition, a generative adversarial network based on Pixel2Pixel was proposed. The generator was a codec structure combining a residual network and an attention mechanism to capture detailed information. The discriminator used a convolutional neural network to discriminate the segmentation results of the generated model and that of the expert. Through the continuously transmitted losses of the generator and discriminator, the generator reached the optimal state of hippocampus segmentation. T1-weighted magnetic resonance imaging scans and related hippocampus labels of 130 healthy subjects from the Alzheimer's disease Neuroimaging Initiative dataset were used as training and test data; similarity coefficient, sensitivity, and positive predictive value were used as evaluation indicators. Results showed that the network model could achieve an efficient automatic segmentation of the hippocampus and thus has practical relevance for the correct diagnosis of diseases, such as Alzheimer's disease.

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in the literature to ascertain the extent to which platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) improved patient outcomes in arthroscopic rotator cuff repair.Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, with a third author resolving any discrepancies. RCTs comparing PRP or PRF to a control in rotator cuff repair were included. Quality of evidence was assessed using the Cochrane Collaboration risk of bias tool. Clinical outcomes were compared using the risk ratio for dichotomous variables and the mean difference for continuous variables. A P value.05 was deemed statistically significant.Included in this review are 23 RCTs with 1440 patients. PRP resulted in significantly decreased rates of retear (15.9% versus 29.0%, respectively; P.0001). Significant results were noted in favor of PRP compared with control based on the Constant score (83.9 versus 81.2, respectively; P = .0006); the University of California, Los Angeles score (31.1 versus 30.2; P.00001); the American Shoulder and Elbow Surgeons score (87.3 versus 84.5; P = .04); and the visual analog scale score (1.3 versus 1.6; P = .01). PRF resulted in an improved Constant score (80.1 versus 80.0, respectively; P = .04) compared with control.The current evidence shows that using PRP in arthroscopic rotator cuff repair can improve pain levels and functional outcome scores while reducing the retear rate after surgery. PRF injection, on the other hand, improves only the Constant score.II; systematic review and meta-analysis of level I and II evidence.

Face detection is to search all the possible regions for faces in images and locate the faces if there are any. Many applications including face recognition, facial expression recognition, face tracking and head-pose estimation assume that both the location and the size of faces are known in the image. In recent decades, researchers have created many typical and efficient face detectors from the Viola-Jones face detector to current CNN-based ones. However, with the tremendous increase in images and videos with variations in face scale, appearance, expression, occlusion and pose, traditional face detectors are challenged to detect various "in the wild" faces. The emergence of deep learning techniques brought remarkable breakthroughs to face detection along with the price of a considerable increase in computation. This paper introduces representative deep learning-based methods and presents a deep and thorough analysis in terms of accuracy and efficiency. We further compare and discuss the popular and challenging datasets and their evaluation metrics. A comprehensive comparison of several successful deep learning-based face detectors is conducted to uncover their efficiency using two metrics: FLOPs and latency. The paper can guide to choose appropriate face detectors for different applications and also to develop more efficient and accurate detectors.

Background. The revascularization of small vessels using drug-eluting stents remains challenging. The use of the drug-coated balloon is an attractive therapeutic strategy in de novo lesions in small coronary vessels, particularly in the diabetic group. This study aimed to assess the outcomes of DCB-only angioplasty in small vessel disease. Methods. A total of 1198 patients with small vessel disease treated with DCB-only strategy were followed. Patients were divided into the diabetic and nondiabetic groups. Clinical and angiographical follow-up were organized at 12 months. The primary endpoints were target lesion failure and secondary major adverse cardiac events. Results. There was a significantly higher rate of target lesion failure among diabetic patients compared to nondiabetic [17 (3.9%) vs. 11 (1.4%), P = 0.006 ], taken separately, the rate of target lesion revascularization significantly differed between groups with a higher rate observed in the diabetic group [9 (2%) vs. 4 (0.5%), P = 0.014 ]. Diabetes mellitus remained an independent predictor for TLF (HR: 2.712, CI: 1.254–5.864, P = 0.011 ) and target lesion revascularization (HR: 3.698, CI: 1.112–12.298, P = 0.033 ) after adjustment. However, no significant differences were observed between groups regarding the target vessel myocardial infarction (0.6% vs. 0.1%, P = 0.110 ) and MACE [19 (4.4%) vs. 21 (2.7%), P = 0.120 ]. Conclusion. Drug-coated balloon-only treatment achieved lower incidence rates of TLF and MACE. Diabetes is an independent predictor for target lesion failure and target lesion revascularization at one year following DCB treatment in small coronary vessels. We observed no significant differences between groups regarding MACE in one year.

This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC). We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups. A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0–1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan–Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia. Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2–3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT.

A simple, efficient, and economical method was developed to fabricate superhydrophobic surfaces on various substrates, including wood, bamboo, cotton, filter paper, sponge, glass, textile, and copper. This method involves synthesizing a two-component modifier solution consisting of SiO2 nanoparticles combined with poly(methylhydrogen)siloxane (PMHS) modification. The superhydrophobicity of the coated surfaces was created by PMHS combined with SiO2 nanoparticles to construct a rough hierarchical structure on the surface of the substrate. All superhydrophobic surfaces were maintained at a relative humidity of 50% for 30 days in an indoor environment and subsequently, the superhydrophobic surfaces were kept minus 20 °C for 24 h. It was confirmed that these surfaces exhibited excellent self-cleaning, oil/water separation, and elimination of underwater oil properties. The method for fabricating superhydrophobic materials proposed in this study will have great potential to prepare large-scale superhydrophobic surfaces for use in ancient building protection.

In the past few years, the prediction models have shown remarkable performance in most biological correlation prediction tasks. These tasks traditionally use a fixed dataset, and the model, once trained, is deployed as is. These models often encounter training issues such as sensitivity to hyperparameter tuning and "catastrophic forgetting" when adding new data. However, with the development of biomedicine and the accumulation of biological data, new predictive models are required to face the challenge of adapting to change. To this end, we propose a computational approach based on Broad learning system (BLS) to predict potential disease-associated miRNAs that retain the ability to distinguish prior training associations when new data need to be adapted. In particular, we are introducing incremental learning to the field of biological association prediction for the first time and proposed a new method for quantifying sequence similarity. In the performance evaluation, the AUC in the 5-fold cross-validation was 0.9400 +/- 0.0041. To better assess the effectiveness of MISSIM, we compared it with various classifiers and former prediction models. Its performance is superior to the previous method. Besides, the case study on identifying miRNAs associated with breast neoplasms, lung neoplasms and esophageal neoplasms show that 34, 36 and 35 out of the top 40 associations predicted by MISSIM are confirmed by recent biomedical resources. These results provide ample convincing evidence of this approach have potential value and prospect in promoting biomedical research productivity.

A smart grid improves power grid efficiency by using modern information and communication technologies. However, at the same time, the system might become increasingly vulnerable to cyberattacks. Among various emerging security problems, a false data injection attack (FDIA) is a new type of attack against the state estimation. In this article, a deep learning‐based identification scheme is developed to detect and mitigate information corruption. The scheme implements a Conditional Deep Belief Network to analyse time‐series input data and leverages captured features to detect the FDIA. The performance of the detection mechanism is validated by using the IEEE standard test system for simulation. Different attack scenarios and parameters are set to demonstrate the feasibility and effectiveness of the developed scheme. Compared with the support vector machine and the multilayer perceptrons, the experimental analyses indicate that the results of the proposed detection mechanism are better than those of the other two in terms of FDIA detection accuracy and robustness.

Although drug-eluting stents are the most common interventional devices for patients with coronary disease, drug-coated balloons (DCBs) represent a novel therapeutic alternative in certain scenarios. This prospective, observational all-comers study explored the clinical outcomes of DCB use in patients with coronary lesions. All patients treated with DCBs were enrolled in this study, including patients with in-stent restenosis (ISR) or de novo lesions. The primary outcome was the target lesion revascularization (TLR) rate at one year. We enrolled 2306 patients with 2660 lesions and performed DCB angioplasty in 399 patients (17.3%) with ISR and 1907 patients (82.7%) with de novo lesions. During follow-up (366 ± 46 days), the TLR rate was lower in the de novo lesion group (1.31%) compared to the ISR group (7.02%) [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.101–0.305, p

Supplemental Digital Content is available in the text., Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan–Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan–Meier analyses of 178 HCC samples revealed that nuclear PGAM2’s high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2’s high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. Some microRNAs (miRNAs) play critical roles in the development of many neurological diseases. This study aims to evaluate the clinical significance and biological function of miR-485-3p in the development and progression of PD. The expression of miR-485-3p in serum of PD patients was analyzed by quantitative real-time PCR (qRT-PCR). LPS-treated microglia BV2 cells were used to mimic neuroinflammation in the pathogenesis of PD. The levels of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, were detected by enzyme-linked immunosorbent assay (ELISA). The diagnosis value of miR-485-3p was evaluated by plotting receiver operating characteristic (ROC) curves. A luciferase reporter assay was performed to demonstrate the interaction between miR-485-3p and FBXO45. The results showed that miR-485-3p was significantly up-regulated in serum of PD patients compared with that in both Alzheimer's disease (AD) and healthy cases, and had diagnostic accuracy for PD screening. The activated microglia BV2 cells induced by LPS also had elevated miR-485-3p, and the knockdown of miR-485-3p inhibited the release of pro-inflammatory cytokines. FBXO protein 45 (FBXO45) served as a potential target of miR-485-3p, which was speculated to mediate the function of miR-485-3p. Our results suggest that the up-regulated expression of miR-485-3p in PD may be a novel diagnostic biomarker for PD. Reducing the expression level of miR-485-3p can inhibit the inflammatory responses of BV2 cells, which indicated that miR-485-3p, as a regulator of neuroinflammation, may have the potential as a therapeutic target in PD.

Aims Anti‐leucine‐rich glioma‐inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by complex manifestations of seizures. Here, we report a new seizure semiology, attempt to classify the disease by semiology type, and explore the metabolic pattern of each group. Methods Anti‐LGI1 AE patients were retrospectively screened between May 2014 and September 2019 in our tertiary epilepsy center. All enrolled patients had seizures during long‐range video electroencephalogram (EEG) recordings, and all patients (except one) underwent [18F] fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) scans. Voxel‐based metabolic analysis and z‐distribution analysis were carried out to determine the metabolic pattern. Results Thirty‐three patients were enrolled. According to the patients’ seizure semiology, we divided the patients into four groups: focal impaired awareness seizures (FIAS, n = 17), faciobrachial dystonic seizures (FBDS)‐only (n = 6), FBDS‐plus (n = 8), and focal aware motor seizures (FAMS) (n = 2). No significant differences were found in the clinical manifestations or accessory tests except for the onset age (FIAS, Dozens of clinical and subclinical seizures were detected in the long‐range video EEG recording of an anti‐LGI1 encephalitis patient with focal aware motor seizures (A). Furthermore, FDG‐PET scans showed a wide range of abnormal metabolic pattern of this patient and patients with other seizure semiologies, which is not limited to the temporal regions and basal ganglia and far beyond our previous interpretation (B).

Objective: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been used as markers of inflammation in mental illness. However, these indices have not been widely used in schizophrenia research in Chinese participants. Our aim was to use these ratios to explore the relationship between schizophrenia and inflammation. Methods: In this retrospective cross-sectional study, we collected total blood cell counts of 549 patients with schizophrenia and 930 healthy controls at Beijing Huilongguan Hospital in October 2019. We analyzed the subjects’ platelet, lymphocyte, monocyte, and neutrophil counts; compared the calculated NLR, MLR, and PLR between patients and healthy controls; and evaluated the correlations with age and gender. Results: Platelet and lymphocyte counts were significantly lower, while NLR and MLR were significantly higher, in patients with schizophrenia compared to healthy controls. Additionally, monocyte count, lymphocyte count, MLR, and NLR were different between male and female subjects. Conclusion: This study supports the inflammatory hypothesis of schizophrenia in the Chinese population.

Background. Subjective cognitive decline (SCD) is the earliest symptom stage of Alzheimer’s disease (AD). Previous studies have shown that the study setting is an important influence factor of SCD. However, the effect of this factor among a Chinese population with SCD is not clear. Here, we aim to compare the clinical characteristics of SCD between a convenience and a population-based sample in China. Methods. We included a convenience sample of 212 SCD subjects and a population-based sample of 110 SCD subjects. We performed univariate analysis to evaluate the between-group differences in sociodemographic characteristics, neuropsychological performance, psychiatric conditions, different cognitive domains, and the SCD-plus criteria. Multiple linear regression model was established, adjusted for sex, age, and education, and compared the neuropsychological performance between the groups. Results. The convenience sample had more years of education, a higher family history of dementia, and higher neuropsychological and anxiety depression score than the population-based sample. Using sex, age, education, group as the independent variables, and neuropsychological score as the dependent variable, multiple linear regression model was established; a statistically significant neuropsychological score difference (MoCA-B, AVLT-H-N4, AVLT-H-N5, AVLT-H-N7, AFT, and STT-B) was found between the two samples. In the SCD cognitive domains, the population-based sample had more complaints about declines in their language and planning domains. For SCD-plus criteria in memory domain, the convenience sample had more complaints, worry, and cognitive decline within the last 5 years, along with medical help-seeking. Conclusion. There were some different characteristics among SCD individuals between convenience samples and population-based samples in China.

This study compared clinical outcomes obtained after single-bundle anterior cruciate ligament (ACL) reconstruction using the anteromedial (AM) and transtibial (TT) techniques, which comprise the conventional transtibial (cTT) and modified transtibial (mTT) techniques. This study included clinical randomized controlled trials and prospective and retrospective controlled trials with AM and TT techniques from the PubMed and Embase databases and the Cochrane Library. All databases were searched from January 2010 to July 2020. Two independent evaluators verified the quality of the included studies using the Cochrane Collaboration’s risk of bias tool and the Newcastle-Ottawa Scale (NOS). Outcome measures analysed included the Lachman test, pivot-shift test, side-to-side difference (SSD), Lysholm score, Tegner activity scale, International Knee Documentation Committee (IKDC) grade and score. Ten randomized controlled trials (RCTs) and 16 prospective and retrospective controlled trials were included with a total of 2202 patients. There were 1180 patients and 1022 patients in the AM and TT groups, respectively. Compared to the cTT group, superior postoperative results were observed in the AM group based on the negative rate of the Lachman test and the pivot-shift test, IKDC grade and score, Lysholm score, Tegner activity scale and SSD (p < 0.05). However, there was no significant difference between the AM and mTT groups (p > 0.05). Compared to the conventional TT technique, the AM technique exhibited superior clinical outcomes. Nevertheless, the modified TT and AM techniques had comparable results. With neither of the techniques (mTT or AM) producing significantly superior outcomes, surgeons can choose either of them depending on their preferences.

Active vision sensing is widely used in intelligent robotic welding for bead detection and tracking. Disturbed by welding noise such as arc light and spatter, it is a hard work to extract the laser stripe and feature values. This paper presents a method for denoising and feature extraction of weld seam profiles with strong welding noise in gas metal arc welding (GMAW) process by using stacked denoising autoencoder (SDAE). This algorithm encodes the images of various butt joints with strong welding noise to several useful intermediate representations, which can be decoded to the image of pure laser stripe in 1-pixel width. The results show little deviations when there are large spatters across the laser stripe. A back propagation neural network (BPNN) is developed to verify the reliability of the intermediate representations gotten from the encoder, in which the intermediate representations are input neurons and the weld seam width is output neuron. The average width error in training dataset and testing dataset is 0.042 mm and 0.061 mm. The results show that this algorithm can extract the weld seam profiles with strong welding noise and extract feature values accurately.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P 

Xikun Wu,1 Weichong Dong,1 Haoran Li,1 Xiuling Yang,1 Yiran Jin,1 Zhiqing Zhang,1 Ye Jiang2 1The Second Hospital of Hebei Medical University, Shijiazhuang City, People’s Republic of China; 2Pharmacy College, Hebei Medical University, Shijiazhuang City, People’s Republic of ChinaCorrespondence: Zhiqing ZhangThe Second Hospital of Hebei Medical University, Department of Pharmacy, 215 Hepingxi Road, Shijiazhuang City, 050000, People’s Republic of ChinaEmail 777yyy@sina.cnYe JiangPharmacy College, Hebei Medical University, 361 Zhangshandong Road, Shijiazhuang City, 050017, People’s Republic of ChinaEmail jiangye@hebmu.edu.cnPurpose: To perform therapeutic drug monitoring (TDM) of total and free plasma valproic acid (VPA) concentrations in pediatric patients with epilepsy and to analyze related factors.Patients and Methods: Pediatric epileptic patients treated in 2015– 2019 in our hospital were assessed. Total and free plasma VPA concentrations were obtained by UPLC and LC-MS/MS, respectively. Regression analysis was performed to examine the associations of free plasma VPA with total plasma VPA and plasma protein binding rate. The impacts of individual situation, CYP2C9 genotype, and drug combination on VPA concentration were examined.Results: Of the 251 patients, 81 had lower total concentrations than effective therapeutic levels; 86 and 31 patients had infections and central nervous system dysplasia, respectively. VPA’s daily doses and free drug concentrations were significantly lower in the CYP2C9 *3/*3 genotype group versus the CYP2C9 *1/*3 and CYP2C9 *1/*1 groups (P< 0.05). Free and total VPA concentrations were linked by Y = 0.0004 X2 + 0.042 X + 0.3035 (r=0.6981); VPA plasma protein binding rate and free VPA concentration were related by Y = 0.0003 X2 - 0.0127 X + 0.9777 (r=0.8136). Both total and free VPA concentrations were significantly decreased in patients simultaneously administered phenobarbital, meropenem and biapenem (P< 0.05), with therapeutic failure after meropenem/biapenem co-administration.Conclusion: Free VPA amounts have nonlinear relationships with total VPA amounts and plasma protein binding rate in epileptic children. Additionally, CYP2C9 *3/*3 expression affects VPA metabolism. Since phenobarbital affects VPA metabolism, TDM is recommended. Meanwhile, carbapenem-co-administration with VPA should be prohibited.Keywords: valproic acid, pediatric patient, free concentration, CYP2C9 gene expression, TDM

Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle–brachial index (ABI) (0.9–1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group ( p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group ( p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

Aerated flow characterized by complex mass transfer processes with multiple hydraulic properties is a common enviro-hydraulics phenomenon, which have a variety of profound effects on aquatic ecosystems and the environment. Accurate prediction of the mass transfer process between air and water is crucial to manage the water ecosystem. In this research, an improved two-phase mass transfer smoothed particle hydrodynamics (ITMT-SPH) model is developed with considering the inherent hydrodynamic equations and transport equations to investigate multiple key factors that have ecological implications such as DO (dissolved oxygen) concentration and TDG (total dissolved gas) level. The established model can eliminate the effects of phase separation and non-physical voids for conventional SPH models, which performs better than conventional grid-based methods in terms of prediction accuracy of hydraulic calculation. In addition, to improve the prediction accuracy of mass transfer calculation, experimental and observed field data from a physical model and a practical project are used to calibrate the source parameter of transport equations. Then, a physical model of Songta Hydropower Station (1:80) is established to simulate DO concentration. At the same time, the practical project of Tongjiezi Hydropower Station is used to explore dynamics of TDG level. Simulation results show that ITMT-SPH can simulate ecological indicators of the aerated flow well. The maximum relative error of DO deficit recovery rate between simulation and experiment is 7.8% downstream of dam of Songta physical model. The predicted result of TDG level downstream of Second Dam is 130–148% for Tongjiezi Project, which is close to the monitoring result (138%). This work provides an important theoretical and technical support for the application of ITMT-SPH model to accurately simulate ecological indicators in the ecosystem management.

In this study, a novel gradient grating period guided-mode resonance (GGP-GMR) biosensor is proposed, and albumin was successfully detected as a test model. The GGP-GMR sensor exhibits a gradient resonant wavelength along the device. At a fixed incident wavelength, light resonates at a specific period such that the light is reflected at this period (or resonant period) and transmitted to other periods. Thus, for a charge-coupled device under the GGP-GMR sensor, a dip-like intensity distribution was measured with a specific pixel of minimum intensity corresponding to the resonant period. The variation in sample concentrations caused changes in the refractive index (RI) on the sensor surface, which induced a shift in the resonant period and in the pixel corresponding to the minimum intensity. A GGP-GMR sensor can achieve a limit of detection of $8.58\times 10^{{-4}}$ RIU within a detection range of sucrose solutions of 0%–60% concentrations that corresponds to the RI from 1.333 to 1.442. In a buffer solution, albumin was successfully detected to measure the clinically relevant concentration. The simple design and easy fabrication of the GGP-GMR sensor combined with its simple readout and optical path design facilitates system miniaturization for handheld devices and its integration with smartphones, which could be beneficial for future point-of-care applications.

Data are limited with regard to the association between low-grade albuminuria (below the threshold of microalbuminuria) and high cardiovascular risk in normoalbuminuric Chinese adults free of cardiovascular disease (CVD).A total of 32 650 participants aged over 40 years from seven regional centers in China were included in this study. The single-void first morning urine sample was collected to measure the urinary albumin to creatinine ratio (UACR) and the data were divided into sex-specific quartiles. The Framingham Risk Score (FRS) was used to identify participants at high risk of developing coronary heart disease (CHD) over the next 10 years and the association between low-grade albuminuria and high 10-year Framingham risk for CHD (FRS ≥20%) was investigated.Among males and females, the prevalence of cardiometabolic risk factors (diabetes, hypertension, and dyslipidemia) increased markedly with the elevation of UACR quartiles. Logistic regression analysis showed that the odds ratios (ORs) for high 10-year risk of CHD increased significantly from the second quartile in males (UACR: 4.78 ~ 7.53 mg/g, OR = 1.21, 95% confidence interval [CI]: 1.05-1.40) and the third quartile in females (UACR: 9.13 ~ 15.04 mg/g, OR = 3.07, 95% CI: 1.75-5.40). Stratified analysis showed that in males, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and hypertension whereas in females, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and with hypertension.Low-grade albuminuria was significantly associated with high 10-year cardiovascular risk among CVD-free and normoalbuminuric Chinese adults.背景: 在无心血管疾病(CVD)且尿蛋白正常的中国成年人群中, 关于低度白蛋白尿(低于微量白蛋白尿阈值)与心血管高危风险的相关性研究数据有限。 方法: 本研究共纳入来自中国7个中心的32650名40岁以上社区人群。收集晨尿测尿微量白蛋白与肌酐的比值(UACR), 分别在男性和女性中进行数据分析, 并根据UACR水平将各性别人群分成四分位。采用Framingham风险评分(FRS)计算参与者未来10年罹患冠心病(CHD)的风险, FRS ≥ 20%者被定义为未来10年患冠心病的风险为高危。建立Logistic回归模型, 分析低度白蛋白尿与未来10年冠心病高危风险的相关性。 结果: 在男性和女性中, 冠心病高危因素如糖尿病、高血压和血脂异常的患病率随着UACR水平的升高而显著增加。Logistic回归分析显示, 从男性UACR第二分位(UACR: 4.78 ~ 7.53 mg/g, OR = 1.21, 95% [CI]: 1.05-1.40)、女性第三分位(UACR:9.13 ~ 15.04 mg/g, OR = 3.07, 95% CI: 1.75-5.40)开始, 随着UACR的升高, 未来10年冠心病高危风险的比值比(OR)明显增加。分层分析显示, 在老年、超重或肥胖、无糖尿病和无高血压的男性以及老年、超重或肥胖、无糖尿病和有高血压的女性中, 这种相关性最为显著。 结论: 在无心血管疾病病史且尿蛋白正常的中国成年人群中, 低度白蛋白尿与未来10年冠心病高危风险显著相关。.

Perovskite solar cells (PSCs) have triggered a research trend in solar energy devices in view of their high power conversion efficiency and ease of fabrication. However, more delicate strategies are still required to suppress carrier recombination at charge transfer interfaces, which is the necessary path to high-efficiency solar cells. Here, a p-p+ homojunction was constructed on basis of NiO film to enhance hole transfer in an inverted planar perovskite solar cell. The homojunction was generated by fabricating a NiO/Cu:NiO bilayer film. The density functional theory calculation demonstrated the charge density difference in the two layers, which could generate a space charge region and a band bending at the junction, and the result was further proved by energy level structure analysis of NiO and Cu:NiO films. The designed homojunction could accelerate the hole transfer and inhibit carrier recombination at the interface between hole transfer layer and perovskite layer. Finally, the inverted planar perovskite solar cell with p-p+ homojunction showed an efficiency of 18.30 % and a high fill factor of 0.81, which were much higher than the counterpart of the PSCs individually using NiO or Cu:NiO as hole transfer layer. This work developed a new structure of hole transport layer to enhance the performance of PSCs, and also provided new ideas for design of charge transfer films.

PURPOSE To demonstrate a proof of concept for the measurement of myocardial oxygen extraction fraction (mOEF) by a cardiovascular magnetic resonance technique. METHODS The mOEF measurement was performed using an electrocardiogram-triggered double-echo asymmetric spin-echo sequence with EPI readout. Seven healthy volunteers (22-37 years old, 5 females) were recruited and underwent the same imaging scans at rest on 2 different days for reproducibility assessment. Another 5 subjects (23-37 years old, 4 females) underwent cardiovascular magnetic resonance studies at rest and during a handgrip isometric exercise with a 25% of maximal voluntary contraction. Both mOEF and myocardial blood volume values were obtained in septal regions from respective maps. RESULTS The reproducibility was excellent for the measurements of mOEF in septal myocardium (coefficient of variation: 3.37%) and moderate for myocardial blood volume (coefficient of variation: 19.7%). The average mOEF and myocardial blood volume of 7 subjects at rest were 0.61 ± 0.05 and 11.0 ± 4.3%, respectively. The mOEF agreed well with literature values that were measured by PET in healthy volunteers. In the exercise study, there was no significant change in mOEF (0.61 ± 0.06 vs 0.62 ± 0.07) or myocardial blood volume (12 ± 6% vs 13 ± 4%) from rest to exercise, as expected. CONCLUSION The implemented cardiovascular magnetic resonance method shows potential for the quantitative assessment of mOEF in vivo. Future technical work is needed to improve image quality and to further validate mOEF measurements.

After cardiac arrest (CA) and resuscitation, the unfolded protein response (UPR) is activated in various organs including the brain. However, the role of the UPR in CA outcome remains largely unknown. One UPR branch involves spliced X-box-binding protein-1 (XBP1s). Notably, XBP1s, a transcriptional factor, can upregulate expression of specific enzymes related to glucose metabolism, and subsequently boost O-linked β-N-acetylglucosamine modification (O-GlcNAcylation). The current study is focused on effects of the XBP1 UPR branch and its downstream O-GlcNAcylation on CA outcome. Using both loss-of-function and gain-of-function mouse genetic tools, we provide the first evidence that activation of the XBP1 UPR branch in the post-CA brain is neuroprotective. Specifically, neuron-specific Xbp1 knockout mice had worse CA outcome, while mice with neuron-specific expression of Xbp1s in the brain had better CA outcome. Since it has been shown that the protective role of the XBP1s signaling pathway under ischemic conditions is mediated by increasing O-GlcNAcylation, we then treated young mice with glucosamine, and found that functional deficits were mitigated on day 3 post CA. Finally, after confirming that glucosamine can boost O-GlcNAcylation in the aged brain, we subjected aged mice to 8 min CA, and then treated them with glucosamine. We found that glucosamine-treated aged mice performed significantly better in behavioral tests. Together, our data indicate that the XBP1s/O-GlcNAc pathway is a promising target for CA therapy.

Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy. The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates. We systematically searched the PubMed and Embase databases from inception to 30 June 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults. Fourteen studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved adults only. The median value of apparent clearance for children (0.074 L/h/kg [range 0.038–0.079]) was higher than that for adults (0.054 L/h/kg [range 0.039–0.061]). Body weight was found to significantly influence the apparent clearance and volume of distribution, whereas renal function influenced the clearance. Likewise, coadministration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9–22%, whereas coadministration with valproate acid decreased it by 18.8%. Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.

The purpose of this study was to establish a protein binding model of unbound valproic acid (VPA) based on Chinese pediatric patients with epilepsy and provide a reference for clinical medication. A total of 313 patients were included and both their total and unbound VPA concentrations (375 pairs of concentrations) were measured. NONMEM software was used for population pharmacokinetic modeling. The stepwise method was used to screen the potential covariates. Goodness-of-fit plot, bootstrap, and visual predictive check were used for model evaluation. In addition, dose recommendations for typical patients aged 0 to 16 years were proposed by Monte Carlo simulations. A one-compartment model of first-order absorption and first-order elimination was used to describe the pharmacokinetic characteristics of unbound VPA, and the linear non-saturable binding equation was introduced to describe the protein binding. Body weight, age-based maturation, and co-medicated with lamotrigine could affect the CL/F of unbound and bound VPA. Model evaluation showed satisfactory robustness of the final model. The dosing regimens for children aged 0 to 16 years were proposed based on the final established model. We developed a population pharmacokinetic model of unbound and bound VPA that took account of protein binding. The VPA dosing regimen in pediatric patients with epilepsy needs to be optimized by the body weight, age, and co-medications.

Introduction: Oculomotor paresis with cyclic spasms (OPCS) is a rare disorder in which the muscles innervated by the third cranial nerve undergo alternating rhythmic spasm and paralysis. This disease is usually noticeable at birth or developing during the first year of life. To date, most of the OPCS cases reported in the English-language literature were Caucasians. Case Presentation: In this study, we review OPCS patients published in China’s high-quality journals and report 1 new case encountered in our clinic. The clinical characteristics of 29 Chinese OPCS patients are summarized. Our review demonstrates the same trend in the analysis values for the onset age, pupil, lid, eye movement, time of cycles, and preferentially involved side in Chinese OPCS patients in comparison with previous reviews. Moreover, we review a case combined with Marcus Gunn Syndrome, a case with rapid relief under oral carbamazepine treatment, and cases with atypical patterns of cyclic changes. Discussion: Our study may broaden the current knowledge and phenotypic spectrum of OPCS.

Hierarchical load forecasting (HLF) is an approach to generate forecasts for hierarchical load time series. The performance of HLF can be improved by optimizing the forecasting model and the hierarchical structure . Previous studies mostly focus on the forecasting model while the hierarchical structure is usually formed by clustering of natural attributes like geography, customer type, or the similarities between load profiles. A major limitation of these natural hierarchical structures is the mismatched objectives between clustering and forecasting. Clustering aims to minimize the dissimilarity among customers of a group while forecasting aims to minimize their forecasting errors. The two independent optimizations could limit the overall forecasting performance. Hence, this paper attempts to integrate the hierarchical structure and the forecasting model by a novel closed-loop clustering (CLC) algorithm. It links the objectives of forecasting and clustering by a feedback mechanism to return the goodness-of-fit as the criterion for the clustering. In this way, the hierarchical structure is enhanced by re-assigning the cluster membership and the parameters of the forecasting models are updated iteratively. The method is comparatively assessed with existing HLF methods. Using the same forecasting model, the proposed hierarchical structure outperforms the bottom-up structure by 52.20%, ensemble-based structure by 26.89%, load-profile structures by 19.90%, respectively.

Single-well shear-wave imaging using a dipole source-receiver system is an important application for detecting geologic structures away from the borehole. This development allows for determining the azimuth information of the structures. Existing analyses, however, focus on the data received at the borehole axis and use the elastic reciprocity theorem to model the borehole radiation and recording. We have extended the existing analyses to model the radiation, reflection, and recording response of the borehole for azimuthally spaced receivers off the borehole axis. By treating the mirror image of the borehole source with respect to the reflector plane as a virtual source, the borehole reception problem was shown to be equivalent to the response of the borehole to the spherical wave incidence from the virtual source, which can be solved using the cylindrical-wave expansion method. An asymptotic solution using the steepest-descent method is obtained if the virtual source is far from the borehole. The analytical solution allows us to analyze the borehole response for azimuthally spaced off-axis receivers. The analysis results agree well with those from 3D finite-difference simulations. With this analysis, one can further model multicomponent shear-wave reflection data from the cross-dipole acoustic tool and study the azimuthal variation characteristics of the data. Our results reveal that, whereas the data characteristics are dominated by those of a dipole, nondipole responses due to the off-axis reception can be observed, the magnitude of the responses depending on the off-axis distance and frequency and on the formation elasticity. The nondipole response characteristics have the potential to resolve the 180°-ambiguity problem in the azimuth determination for dipole shear-wave imaging. Our findings, therefore, provide new information for shear-wave reflection imaging analysis and development.

Thermal treatment is a widely applied food processing technology in the meat industry due to its convenience. However, the interpretation of the changes in the bacterial community and quality properties in the thermal processed meat products have not been well established. Therefore, the effects of thermal treatment on the quality characteristics and bacterial communities in meatballs during storage at 4°C were investigated, which will provide a more comprehensive understanding of the influence of thermal treatment on the meat quality. Thermal treatment (121°C, 15 min) decreased the initial total viable bacterial counts by 2.1 log CFU/g and the diversity of the initial bacterial communities in meatballs. Compared with the thermal treatment group, a significantly more rapidly increasing trend of total volatile basic nitrogen and a decreasing trend of pH were observed in the control group. At the end of storage, the bacterial community was dominated by Streptococcus, Acinetobacter and Pseudomonas in the thermal treatment meatballs, whereas Pseudomonas, Pantoea, and Serratia. dominated the bacterial community of the control group. Besides, the predicted metabolic pathways revealed high levels of carbohydrate, amino acid, and lipid metabolism in the control group. This finding could contribute to a deep understanding of the influence of thermal treatment on the meat quality. Moreover, these results could provide a theoretical foundation for the development of alternative and novel nonthermal processing technologies for use in the meat industry., The findings of this study demonstrated that thermal treatment (121°C, 15 min) could significantly decrease bacterial community diversity and the growth of potential spoilage bacteria in meatballs. In particular, thermal treatment could largely decrease the relative abundance of bacterial metabolic pathways in meatballs, such as carbohydrate, amino acid, and lipid metabolism to maintain the freshness of meatballs during storage.

BACKGROUND The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown. AIM To evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments. METHODS Electronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline. RESULTS Nineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups. CONCLUSION Treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand the relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery by using ferumoxytol-enhanced MRI and macrin in an ATC mouse model. Materials and Methods ATC tumors were generated in 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors, or intravenously to model hematogenous metastasis, and prospectively enrolled randomly into treatment cohorts (

Photonic crystals (PCs) have attracted intense interest for sensing applications. Photonic crystal hydrogels (PCHs) consist of both periodic PCs and stimuli-responsive hydrogels, which can act as a sensing system for the detection of specific analytes. In PCHs, the hydrogel system undergoes volume phase transitions (VPT, swelling or shrinkage) upon exposure to external stimuli. The VPT of the hydrogel causes the photonic stopband of the PCs within the hydrogel to change, which shifts the Bragg diffraction peak wavelengths. Based on this sensing mechanism, a variety of PCH sensors that can respond to external stimuli, such as humidity, temperature, pH, hazardous chemicals and biological species, have been reported. In this review, we overview the response mechanism, preparation methods, and biosensing applications of three-dimensional (3D) and two-dimensional (2D) PCHs. 3D and 2D PCH biosensors are systematically summarized according to the types of the target analytes. At the end of this review, we also propose the prospects of PCHs in the field of biosensing.

Postmenopausal osteoporosis (PMOP) is one of the most common metabolic bone diseases in postmenopausal women. Increasing evidence has indicated that microRNAs (miRNAs) play vital regulatory roles during osteoporosis progression. This study aimed to investigate the potential function of miR-23b-3p in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs). PMOP was induced in mice by bilateral ovariectomy. X-ray absorptiometry was applied to detect BMD and BMC in PMOP mice. Luciferase reporter assay and RIP assay were utilized to investigate the relationship between miR-23b-3p and MRC2. We found the upregulation of miR-23b-3p in bone tissues of PMOP mice. Silencing of miR-23b-3p relieved PMOP in mice. Moreover, miR-23b-3p knockdown facilitated the osteogenic differentiation of hMSCs by increasing the expression of Runx2, OCN, Osterix and promoting ALP activity. Mechanistically, MRC2 is a downstream target gene of miR-23b-3p. MRC2 knockdown significantly rescued the promoting effect of lenti-miR-23b-3p inhibitor on osteogenic differentiation of hMSCs. Furthermore, miR-23b-3p targeted MRC2 to inhibit the Wnt/β-catenin pathway during the osteogenic differentiation of hMSCs. In summary, inhibition of miR-23b-3p alleviates PMOP by targeting MRC2 to inhibit the Wnt/β-catenin signaling, which may provide a novel molecular insight for osteoporosis therapy.

To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) for colorectal neoplasms. We retrospectively reviewed the medical records of 991 consecutive patients who underwent ESD for colorectal neoplasms at our hospital from January 2007 to November 2016. Delayed post-ESD bleeding was defined as bleeding within 6 h to 30 days after ESD that resulted in either of the three situations: overt hematochezia, bleeding spots confirmed by repeat colonoscopy, or the requirement of a blood transfusion. Delayed bleeding was furtherly separated into early and late delayed bleeding by the end of post-ESD day 2. We analyzed the relationship between delayed bleeding and candidate factors including patient-, lesion-, and treatment-related details. Delayed post-ESD bleeding was found in 47 patients (4.7%), of which 18 cases were late delayed bleeding. Among all patients, 14 patients required a second colonoscopy, and 2 other patients were transferred to surgery. Univariate analysis revealed that patients with hypertension (p = 0.017) and using hot biopsy forceps for wound management (p = 0.028) were significantly associated with late delayed bleeding. Both risk factors remained significant after multivariate analysis: hypertension (OR 2.829, 95% CI 1.101–7.265, p = 0.031), hot biopsy forceps (OR 2.873, 95% CI 1.013–8.147, p = 0.047). Using hot biopsy forceps was also the significant risk factor for late delayed bleeding compared with early delayed bleeding. Patient with hypertension and using hot biopsy forceps for wound management during procedure call for attention on high risk of delayed post-ESD bleeding. Therefore, additional perioperative treatment is recommended in patients with these risk factors.

Background Cryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF. Objective Atrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study. Methods In this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12‐lead electrocardiogram, a 24‐h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits. Results As of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter‐free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter‐free survival. Conclusions Although CBA and RFA are both effective in left atrial electrical and structural reverse‐remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long‐term follow‐up, there was no significant intergroup difference.

Peer-to-peer (P2P) energy market has emerged as a promising way to absorb local generations. However, unregulated P2P transactions are likely to exacerbate voltage violations at distribution networks. The challenge is how to ensure P2P markets to flourish whilst maintaining system voltages within the stator limits. This study proposes a distributed-hierarchical control structure consisting of a central controller and peer controllers to address the challenge. The central controller computes the optimised P2P transaction levels and the nodal voltage references simultaneously and sends the outcomes to the peers as routing-update messages at regular intervals. The peer controllers are developed based on individual phase decupled P–Q theory where two individual channels follow the optimised transaction levels and nodal voltage references. The peers, also, apply a current limit strategy to release the network capacity and improve voltage profiles when confronting with short-term voltage magnitude variations between the two update intervals. A case-study-based investigation shows that reactive power contributions improve the power transaction levels up to 30% while the node voltage violations are reduced. The effectiveness of the proposed strategy is validated using simulation and compared with state-of-the-art voltage mitigation methodologies over the IEEE 19-bus system.

Inflammation is known to play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). T cell immunoglobulin and mucin domain-3 (Tim-3) has emerged as a critical regulator of adaptive and innate immune responses, and has been identified to play a vital role in certain inflammatory diseases; The present study explored the effect of Tim-3 on inflammatory responses and detailed mechanism in EBI following SAH. We investigated the effects of Tim-3 on SAH models established by endovascular puncture method in Sprague-Dawley rats. The present studies revealed that SAH induced a significant inflammatory response and significantly increased Tim-3 expression. Tim-3-AAV administration aggravated neurocyte apoptosis, brain edema, blood-brain barrier permeability, and neurological dysfunction; significantly inhibited Nrf2 expression; and increased HMGB1 expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-17, and IL-18. However, Tim-3 siRNA or NK252 administration abolished the pro-inflammatory effects of Tim-3. Our results indicate a function for Tim-3 as a molecular player that links neuroinflammation and brain damage after SAH. We reveal that Tim-3 overexpression deteriorates neuroinflammatory and neurocyte apoptosis after subarachnoid hemorrhage through the Nrf2/HMGB1 signaling pathway in rats.

BACKGROUND Patients with ischemic stroke who have H-type hypertension are at an increased risk of recurrent stroke. The relationship between risk perception and lifestyle in these patients has not been fully explored. The objective of this study is to investigate risk perceptions and lifestyles among H-type hypertensive ischemic stroke patients and explore their relationships. METHODS A total of 314 hypertensive ischemic stroke patients were divided according to homocysteine (Hcy) level into the normal Hcy and high Hcy group using convenience sampling. The high Hcy group was further divided into the perceived or non-perceived group based on the patients' risk perceptions. The Essen Stroke Risk Score and the Health Behavior Scale were used to investigate the patients' risk perceptions and lifestyles. RESULTS The perceived risk factors in the high Hcy group included hypertension, diabetes, alcohol consumption, hyperlipidemia, and smoking, which showed no significant difference with those in the normal Hcy group. The high Hcy group had a total lifestyle score of (2.54±0.42). The perceived group had a better lifestyle than the non-perceived group; however, only blood pressure monitoring compliance showed a significant difference between the groups (P

The polyvinylidene fluoride hollow fibre membrane air dehumidification tests were carried out between the liquid desiccant solutions and the wet air. Three liquid desiccant solutions of LiBr solution (50%), LiCl solution (35%) and CaCl2 solution (40%) were tested under different wet air conditions. The results showed that all the membrane dehumidification processes were stable. The air moisture content in the outlet of the membrane was maintained as 6.5 g/kg (da)–8.2 g/kg (da) when the air moisture content in the inlet of the membrane was operated from 17.1 g/kg (da) to 32.4 g/kg (da). The dehumidification amount of LiBr solution (50%) and LiCl solution (35%) was more productive. On this basis, a membrane-based air pre-dehumidification process for the capillary radiant air conditioning system was built. Since the ideal dew point temperature range of the indoor air is below 14–17°C according to the cold supply water, all the air moisture content at the membrane outlet is much lower than that of the ideal dew point temperature range, which means non-condensing occurs in the capillary tube surface. The membrane-based air pre-dehumidification process can easily form an adaptive regulation process of humidity with the capillary radiant air conditioning system under different environmental parameters.

Background. Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. Methods. Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. Results. Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. Conclusion. ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.

Aims Morphological abnormalities are present in patients with developmental dysplasia of the hip (DDH). We studied and compared the pelvic anatomy and morphology between the affected hemipelvis with the unaffected side in patients with unilateral Crowe type IV DDH using 3D imaging and analysis. Methods A total of 20 patients with unilateral Crowe-IV DDH were included in the study. The contralateral side was considered normal in all patients. A coordinate system based on the sacral base (SB) in a reconstructed pelvic model was established. The pelvic orientations (tilt, rotation, and obliquity) of the affected side were assessed by establishing a virtual anterior pelvic plane (APP). The bilateral coordinates of the anterior superior iliac spine (ASIS) and the centres of hip rotation were established, and parameters concerning size and volume were compared for both sides of the pelvis. Results The ASIS on the dislocated side was located inferiorly and anteriorly compared to the healthy side (coordinates on the y-axis and z-axis; p = 0.001; p = 0.031). The centre of hip rotation on the dislocated side was located inferiorly and medially compared to the healthy side (coordinates on the x-axis and the y-axis; p < 0.001; p = 0.003). The affected hemipelvis tilted anteriorly in the sagittal plane (mean 8.05° (SD 3.57°)), anteriorly rotated in the transverse plane (mean 3.31° (SD 1.41°)), and tilted obliquely and caudally in the coronal plane (mean 2.04° (SD 0.81°)) relative to the healthy hemipelvis. The affected hemipelvis was significantly smaller in the length, width, height, and volume than the healthy counterpart. (p = 0.014; p = 0.009; p = 0.035; p = 0.002). Conclusion Asymmetric abnormalities were identified on the affected hemipelvis in patients with the unilateral Crowe-IV DDH using 3D imaging techniques. Improved understanding of the morphological changes may influence the positioning of the acetabular component at THA. Acetabular component malpositioning errors caused by anterior tilt of the affected hemi pelvis and the abnormal position of the affected side centre of rotation should be considered by orthopaedic surgeons when undertaking THA in patients with Crowe-IV DDH. Cite this article: Bone Joint J 2020;102-B(10):1311–1318.

Background. The relationship between fasting blood glucose (FBG) and microvascular obstruction (MVO) after primary percutaneous coronary intervention (PCI) remains unclear in nondiabetic patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to determine the predictive value of FBG in MVO in nondiabetic STEMI patients. Methods. A total of 108 nondiabetic STEMI patients undergoing primary PCI were enrolled in this study. The patients were classified into either the MVO group or non-MVO group based on cardiac magnetic resonance imaging (CMR). Results. FBG in the MVO group was higher than in the non-MVO group. Univariate analysis showed that FBG, peak high-sensitive troponin T (TnT), pre-PCI thrombolysis in myocardial infarction (pre-PCI TIMI) flow, left ventricular ejection fraction (LVEF), infarction size, left ventricular end-diastolic diameter (LVEDd), left ventricular end-diastolic volume (LVEDV), and global longitudinal strain (GLS) were likely predictive factors of MVO. After adjustment for other parameters, FBG, peak TnT, LVEF, and LVEDV remained independent predictors for MVO. Conclusion. FBG was independently associated with MVO in nondiabetic STEMI patients.

External evaluation is an important issue in the population pharmacokinetic analysis of antibiotics. The purpose of this review was to summarize the current approaches and status of external evaluations and discuss the implications of external evaluation results for the future individualization of dosing regimens. We systematically searched the PubMed and EMBASE databases for external evaluation studies of population analysis and extracted the relevant information from these articles. A total of 32 studies were included in this review. Vancomycin was investigated in 17 (53.1%) articles and was the most studied drug. Other studied drugs included gentamicin, tobramycin, amikacin, amoxicillin, ceftaroline, meropenem, fluconazole, voriconazole, and rifampicin. Nine (28.1%) studies were prospective, and the sample size varied widely between studies. Thirteen (40.6%) studies evaluated the population pharmacokinetic models by systematically searching for previous studies. Seven (21.9%) studies were multicenter studies, and 27 (84.4%) adopted the sparse sampling strategy. Almost all external evaluation studies of antibiotics (93.8%) used metrics for prediction-based diagnostics, while relatively fewer studies were based on simulations (46.9%) and Bayesian forecasting (25.0%). The results of external evaluations in previous studies revealed the poor extrapolation performance of existing models of prediction- and simulation-based diagnostics, whereas the posterior Bayesian method could improve predictive performance. There is an urgent need for the development of standards and guidelines for external evaluation studies.