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This article presents a framework for real-time analysis and visualization of ballet dance movements performed within a Cave Virtual Reality Environment (CAVE). A Kinect sensor captures and extracts dance-based movement features, from which a topology preserved "posture space" is constructed using a spherical self-organizing map (SSOM). Recordings of dance movements are parsed into gestural elements by projection onto the SSOM to form unique trajectories in posture space. Dependencies between postures in a trajectory are modeled using a Markovian empirical transition matrix, which is then used to recognize attempted movements. This allows for quantitative assessment and feedback of a student's performance, delivered using concurrent, localized visualizations together with a performance score based on incremental dynamic time warping (IDTW).

Soybean [Glycine max (L.) Merr.] provides a rich source of plant protein and oil worldwide. The commercial use of transgenic technology in soybean has become a classical example of the application of biotechnology to crop improvement. Although genetically modified soybeans have achieved commercial success, hybrid soybean breeding is also a potential way to increase soybean yield. Soybean cytoplasmic male-sterile (CMS) lines have been used in three-line hybrid breeding systems, but their application to exploiting soybean heterosis has been limited by rare germplasm resource of sterile lines. The generation of various genetic diversity male-sterile soybean lines will help to overcome the shortcoming. In this study, we used targeted editing of AMS homologs in soybean by CRISPR/Cas9 technology for the first time to generate stable male-sterile lines. Targeted editing of GmAMS1 resulted in a male-sterile phenotype, while editing of GmAMS2 failed to produce male-sterile lines. GmAMS1 functions not only in the formation of the pollen wall but also in the controlling the degradation of the soybean tapetum. CRISPR/Cas9 technology could be used to rapidly produce stable male-sterile lines, providing new sterile-line materials for soybean hybrid breeding systems.

Objectives This study evaluated the feasibility and safety of total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft on zone 0 landing for aortic arch pathologies. Methods Between June 2016 and October 2019, 37 consecutive patients underwent total endovascular arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing. Outcomes included technical success, perioperative and follow-up morbidity and mortality, and branch artery patency. Results During the study period, 37 patients were treated with total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft. Twenty-one (56.8%) patients were diagnosed with aortic dissections, 15 (40.5%) patients with aneurysms, and 1 (2.7%) patient required reintervention due to endoleak and sac expansion from previous thoracic endovascular aortic repair for thoracoabdominal aneurysm. The proximal landing zone for all patients were in zone 0, and all branch arteries of aortic arch were reconstructed. Technical success was achieved in 34 cases (91.9%). Three (8.1%) patients had fenestrations misaligned with target arteries, and the chimney technique was applied as a complementary measure. Thirty-day mortality rate was 5.4% (n=2). Thirty-day stroke rate was 5.4% (n=2). Thirty-day reintervention rate was 2.7% (n=1). At a median follow-up of 20 months (range, 3–49 months), 5 (13.5%) patients died, including 2 aortic-related deaths, 1 nonaortic-related death, and 2 deaths of unknown reason. One (2.7%) patient had stroke. Four patients (10.8%) had reintervention during the follow-up, including 2 cases of left subclavian artery occlusion and 2 cases of type II endoleak. The estimated survival (±SE) at 2 years was 72.4%±9.7% (95% CI 53.4%–91.4%). The estimated freedom from reintervention (±SE) at 2 years was 87.4%±5.9% (95% CI 75.84%–98.96%). Conclusions Total endovascular aortic arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing is an alternate option for the treatment of aortic arch pathologies in experienced centers.

Our proposed integrated evaluation method for the grouting effect in karst areas is based on the cloud model (CM), the analytic hierarchical process (AHP), and a fuzzy comprehensive evaluation system. Our method fully considers the fuzziness and randomness of the evaluation indices, and bridges the gap between qualitative information and a quantitative evaluation value. The evaluation index system for the grouting effect is established by integrating metrics related to the construction technology, apparent parameters, and observational data from inspection holes and geophysical exploration techniques. First, the weight of each index is calculated using the AHP, which has been modified by the CM. Then, we calculate the cloud model membership degree for each index. Finally, we determine the comprehensive evaluation level by examining the similarity measures between the various cloud models. In this case study, we use our integrated method to evaluate the initial results of the grouting treatment project in the China Resources Cement (Pingnan) Limestone Mine. Our results are validated by subsequent monitoring results for this project. This study provides valuable insight into the treatment of water inflow in karst areas.

Aims This study aims to develop and verify a physiologically based pharmacokinetic (PBPK) population model for the Chinese geriatric population in Simcyp. Methods Firstly, physiological information for the Chinese geriatric population was collected and later employed to develop the Chinese geriatric population model by recalibration of corresponding physiological parameters in the Chinese adult population model available in Simcyp (i.e., Chinese healthy volunteer model). Secondly, drug-dependent parameters were collected for six drugs with different elimination pathways (i.e., metabolized by CYP1A2, CYP3A4 or renal excretion). The drug models were then developed and verified by clinical data from Chinese adults, Caucasian adults and Caucasian elderly subjects to ensure that drug-dependent parameters are correctly inputted. Finally, the tested drug models in combination with the newly developed Chinese geriatric population model were applied to simulate drug concentration in Chinese elderly subjects. The predicted results were then compared with the observations to evaluate model prediction performance. Results Ninety-eight per cent of predicted AUC, 95% of predicted Cmax , and 100% of predicted CL values were within two-fold of the observed values, indicating all drug models were properly developed. The drug models, combined with the newly developed population model, were then used to predict pharmacokinetics in Chinese elderly subjects aged 60-93. The predicted AUC, Cmax , and CL values were all within two-fold of the observed values. Conclusion The population model for the Chinese elderly subjects appears to adequately predict the concentration of the drug that was metabolized by CYP1A2, CYP3A4 or eliminated by renal clearance.

In order to solve the problem that the global and local generated countermeasure network cannot inpaint the random irregular large holes, and to improve the standard convolution generator, which demonstrates the defects of color difference and blur, a network architecture of inpainting irregular large holes in an image based on double discrimination generation countermeasure network is proposed. Firstly, the image generator is a U-net architecture defined by partial convolution. The normalized partial convolution only completes the end-to-end mask update for the effective pixels. The skip link in U-net propagates the context information of the image to the higher resolution, and optimizes the training results of the model with the weighted loss function of reconstruction loss, perception loss and wind grid loss. Subsequently, the adversary loss function, the dual discrimination network including the synthetic discriminator and the global discriminator are trained separately to judge the consistency between the generated image and the real image. Finally, the weighted loss functions are trained together with generating network and double discrimination network to further enhance the detail and overall consistency of the inpainted area and make the inpainted results more natural. The simulation experiment is carried out on the Place 365 standard database. The subjective and objective experimental results show that the results of the proposed method has reasonable overall and detail semantic consistency than those of the existing methods when they are used to repair random, irregular and large-area holes. The proposed method effectively overcomes the defects of blurry details, color distortion and artifacts.

Hand pose estimation in 3D space from a single RGB image is a highly challenging problem due to self-geometric ambiguities, diverse texture, viewpoints, and self-occlusions. Existing work proves that a network structure with multi-scale resolution subnets, fused in parallel can more effectively shows the spatial accuracy of 2D pose estimation. Nevertheless, the features extracted by traditional convolutional neural networks cannot efficiently express the unique topological structure of hand key points based on discrete and correlated properties. Some applications of hand pose estimation based on traditional convolutional neural networks have demonstrated that the structural similarity between the graph and hand key points can improve the accuracy of the 3D hand pose regression. In this paper, we design and implement an end-to-end network for predicting 3D hand pose from a single RGB image. We first extract multiple feature maps from different resolutions and make parallel feature fusion, and then model a graph-based convolutional neural network module to predict the initial 3D hand key points. Next, we use 2D spatial relationships and 3D geometric knowledge to build a self-supervised module to eliminate domain gaps between 2D and 3D space. Finally, the final 3D hand pose is calculated by averaging the 3D hand poses from the GCN output and the self-supervised module output. We evaluate the proposed method on two challenging benchmark datasets for 3D hand pose estimation. Experimental results show the effectiveness of our proposed method that achieves state-of-the-art performance on the benchmark datasets.

BACKGROUND: Nowadays, the total knee arthroplasty (TKA) technique plays an important role in surgical treatment for patients with severe knee osteoarthritis (OA). However, there are still several key issues such as promotion of osteotomy accuracy and prosthesis matching degree that need to be addressed. OBJECTIVE: It is significant to construct an accurate three-dimensional (3D) geometric anatomy structure model of subject-specific human knee joint with major bone and soft tissue structures, which greatly contributes to obtaining personalized osteotomy guide plate and suitable size of prosthesis. METHODS: Considering different soft tissue structures, magnetic resonance imaging (MRI) scanning sequences involving two-dimensional (2D) spin echo (SE) sequence T1 weighted image (T1WI) and 3D SE sequence T2 weighted image (T2WI) fat suppression (FS) are selected. A 3D modeling methodology based on computed tomography (CT) and two sets of MRI images is proposed. RESULTS: According to the proposed methods of image segmentation and 3D model registration, a novel 3D knee joint model with high accuracy is finally constructed. Furthermore, remeshing is used to optimize the established model by adjusting the relevant parameters. CONCLUSIONS: The modeling results demonstrate that reconstruction and optimization model of 3D knee joint can clearly and accurately reflect the key characteristics, including anatomical structure and geometric morphology for each component.

Taking the Hejing limestone mining area of Guangxi Huarun Cement (Pingnan) Company as the research background, the method for water gushing runoff zones of open pit mining area is determined based on numerical simulation and field test. First of all, the calculation model of groundwater movement in open pit mining area is established by the equivalent continuous medium model. Then, calculation parameters of the model are reasonably valued through analyzing the development of karst degree, tracer tests, and pumping tests in drilling holes. Secondly, three existence forms of groundwater seepage field are put forward, and the distribution of groundwater runoff zones is determined by using numerical simulation to analyze the groundwater seepage field influence rules of water accumulation points (such as private mining pit). Thirdly, the results are verified by field tests. The water source and ground water connection in open pit mining area are determined. The results show that (1) the water gushing in the mining area mainly comes from the east and the south. The groundwater flow in the east is uniform, and the most of groundwater is fissure water gushing. (2) The groundwater flow in the south of the mining area is banded, and the most of groundwater is pipe gushing. The results of this research provide a theoretical basis for locating the groundwater runoff zones in karst open pit mining areas.

Chinese cabbage, belonging to Brassica rapa species, is an important vegetable in Eastern Asia. It is well known that Chinese cabbage is quite recalcitrant to genetic transformation and the transgenic frequency is generally low. The lack of an efficient and stable genetic transformation system for Chinese cabbage has largely limited related gene functional studies. In this study, we firstly developed a regeneration system for Chinese cabbage by optimizing numerous factors, with 93.50% regeneration rate on average. Based on this, a simple and efficient Agrobacterium-mediated genetic transformation method was established, without pre-culture procedure and concentration adjustment of hormone and AgNO3 in co-cultivation and selection media. Using this system, transformants could be obtained within 3.5 to 4.0 months. Average transformation frequency is up to 10.83%. The establishment of this simple and efficient genetic transformation method paved the way for further gene editing and functional studies in Chinese cabbage.

Objective. The aim of this systematic review was to summarize and evaluate the existing evidence on the effectiveness and safety of acupuncture in relieving chronic pain-related depression (CPRD). Methods. We searched seven online databases to identify eligible randomized controlled trials (RCTs) of acupuncture for CPRD published before September 2020. We included studies that used acupuncture as the intervention group, with or without a control group, and the control group was treated with conventional drugs. Meta-analysis was performed using RevMan 5.3 software. For outcomes, assessments were performed using the Hamilton Depression Scale (HAMD), Visual Analogue Scale (VAS), and adverse events. Results. Eight studies involving 636 participants were identified and included in the meta-analysis. The results showed that single acupuncture treatment and drug treatment have the same effect in improving the HAMD score (MD = −0.14, 95% CI = [−0.88, 0.59], P = 0.71) and alleviating the VAS score (MD = −0.42, 95% CI = [−1.10, −0.27], P = 0.23), but acupuncture treatment is safer (OR = 0.03, 95% CI = [0.01, 0.21], P = 0.0003). In addition, acupuncture combined with drugs (control group) is more beneficial than single-drug treatment in improving the HAMD score (MD = −2.95, 95% CI = [−3.55, −2.36], P P = 0.0004). Conclusion. Acupuncture is an effective and safe treatment for CPRD, and acupuncture combined with drug therapy is more effective than single-drug therapy. Nevertheless, the conclusions were limited due to the low quality and a small number of included studies.

Purpose The identification of HER2 overexpression in a subset of gastric adenocarcinoma (GA) patients represents a significant step forward in unveiling the molecular complexity of this disease. The predictive and prognostic value of HER2 amplification in advanced HER2 inhibitor-treated GA patients has been investigated. However, its predictive value in resectable patients remains elusive. Methods We enrolled 98 treatment-naïve resectable Chinese GA patients with HER2 overexpression assessed using IHC. Capture-based targeted sequencing using a panel consisting of 41 gastrointestinal cancer-related genes was performed on tumor tissues. Furthermore, we also investigated the correlation between HER2 copy number (CN) and survival outcomes. Results Of the 98 HER2-overexpressed patients, 90 had HER2 CN amplification assessed using next-generation sequencing, achieving 92% concordance. The most commonly seen concurrent mutations were occurring in TP53, EGFR and PIK3CA. We found HER2 CN as a continuous variable was an independent predictor associated with DFS (p = 0.029). Our study revealed HER2 CN-high patients showed a trend of intestinal-type GA predominant (p = 0.075) and older age (p = 0.07). The median HER2 CN was 15.34, which was used to divide the cohort into CN-high and CN-low groups. Patients with high HER2 CN had a significantly shorter DFS than patients with low HER2 CN (p = 0.002). Furthermore, HER2 CN as a categorical variable was also an independent predictor associated with DFS in patients. Conclusion We elucidated the mutation spectrum of HER2-positive resectable Chinese GA patients and the association between HER2 CN and DFS. Our work revealed HER2 CN as an independent risk factor predicted unfavorable prognosis in HER2-positive GA patients and allowed us to further stratify HER2-positive resectable GA patients for disease management.

In order to evaluate the effect of seismic isolation on random seismic response characteristics of a track-bridge system, in this paper, a three-dimensional detailed nonlinear dynamic model consists of rail, CRTS II slab ballastless track, high-speed railway simple supported bridges, isolated bearings, piers, pile foundations from top to bottom, is established by OpenSEES. The stochastic process of ground motion constructed by the random harmonic function is taking as random excitation, and the probability density evolution method (PDEM) is applied to investigate and analyze the system from the random perspective. On this basis, the influence of FPB bearing and the different FPB parameters (such as equivalent radius) on the random seismic response of the track-bridge system is studied. Thereby, aplenty probabilistic information (probability density evolution function, mean value and standard deviation) can be gained of seismic response of isolated bridges with different isolation parameters and non-isolated bridges of the high-speed railway track-bridge system under the excitation of random earthquakes by case study. Through the comparison of random seismic responses of non-isolated bridge and isolated bridges with different parameters under random ground motions, the favorable and unfavorable effects of seismic isolation for high-speed railway bridges are explored and demonstrated from a random point of view. The comparison of the random seismic response under different cases are discussed and significant outcomes are drawn. Results show that: The use of isolation bearing can reduce the response of track structure and pier, but meanwhile, increase the response of bearings. The change of the equivalent radius of the isolation bearing has no obvious influence on the random response of the pier and the track structure, but will to some extent bring the change of the bearing response. The results can be used for the seismic design and maintenance of the railway high-speed bridge.

Vascular remodeling is an initial step in the development of hypertension. Limb remote ischemic conditioning (LRIC) is a physiological treatment that induces endogenous protective effect during acute ischemic injury. However, the impact of long-term LRIC on hypertension, a chronic disease, is unknown. In this study, we aimed to investigate the LRIC effect on blood pressure and vascular remodeling in spontaneously hypertensive rat (SHR) model and patients with prehypertension and early-stage hypertension. LRIC of rats was performed once a day for 6-weeks. Blood pressure, vascular remodeling (cross-sectional area, extracellular deposition, and smooth muscle cell area), inflammation (inflammatory factors, and inflammatory cells) were compared among normotensive Wistar-Kyoto rats (WKY), WKY RIC group, SHR control group, and SHR RIC. Long-term LRCI treatment (twice a day for 4-weeks) was performed on patients with prehypertension or early-stage hypertension. Blood pressure and pulse wave velocity (PWV) were analyzed before and after LRIC treatment. LRIC treatment decreased blood pressure in SHR (n = 9-10). LRIC ameliorated vascular remodeling by decreasing cross-sectional area, suppressing deposition of the extracellular matrix, and hypertrophy of smooth muscle cell in conduit artery and small resistance artery (n = 7). LRIC decreased proinflammatory factors while increasing the anti-inflammatory factors in the circulation (n = 5). LRIC decreased circulating monocyte and natural killer T-cell levels (n = 5). Furthermore, LRIC treatment decreased blood pressure and improved vascular stiffness in patients (n = 20). In conclusion, long term LRIC could decrease blood pressure and ameliorate vascular remodeling via inflammation regulation. LRIC could be a preventive treatment for people with blood pressure elevation or prehypertension.

Although deep learning algorithms have been widely used, their performance depends heavily on a good set of hyperparameters. This article presents an efficient Hyperband and trust-region-based mode...

To preliminarily develop physiologically based population models for Chinese renal impairment patients and to evaluate the prediction performance of new population models by renally cleared antibacterial drugs. First, demographic data and physiological parameters of Chinese renal impairment patients were collected, and then the coefficients of the relative demographic and physiological equation were recalibrated to construct the new population models. Second, drug‐independent parameters of ceftazidime, cefodizime, vancomycin, and cefuroxime were collected and verified by Chinese healthy volunteers, Caucasian healthy volunteers, and Caucasian renal impairment population models built in Simcyp. Finally, the newly developed population models were applied to predict the plasma concentration of four antibacterial drugs in Chinese renal impairment patients. The new physiologically based pharmacokinetic (PBPK) population models can predict the main pharmacokinetic parameters, including area under the plasma concentration–time curve extrapolated to infinity (AUCinf), renal clearance (CLr), and peak concentration (C max), of ceftazidime, cefodizime, vancomycin, and cefuroxime following intravenous administrations with less than twofold error in mild, moderate, and severe Chinese renal impairment patients. The accuracy and precision of the predictions were improved compared with the Chinese healthy volunteers and Caucasian renal impairment population models. The PBPK population models were preliminarily developed and the first‐step validation results of four antibacterial drugs following intravenous administration showed acceptable accuracy and precision. The population models still need more systematic validation by using more drugs and scenarios in future studies to support their applications on dosage recommendation for Chinese renal impairment patients., The PBPK population models of Chinese renal impaired patients were preliminarily developed by employing demographic and physiological parameters of Chinese patients and results of first steps towards verification by four antibacterial drugs following IV administration showed acceptable accuracy and precision in Chinese patients with mild, moderate, and severe renal impairment.

Visual Question Answering (VQA) is a multimodal research related to Computer Vision (CV) and Natural Language Processing (NLP). How to better obtain useful information from images and questions and give an accurate answer to the question is the core of the VQA task. This paper presents a VQA model based on multimodal encoders and decoders with gate attention (MEDGA). Each encoder and decoder block in the MEDGA applies not only self-attention and crossmodal attention but also gate attention, so that the new model can better focus on inter-modal and intra-modal interactions simultaneously within visual and language modality. Besides, MEDGA further filters out noise information irrelevant to the results via gate attention and finally outputs attention results that are closely related to visual features and language features, which makes the answer prediction result more accurate. Experimental evaluations on the VQA 2.0 dataset and the ablation experiments under different conditions prove the effectiveness of MEDGA. In addition, the MEDGA accuracy on the test-std dataset has reached 70.11%, which exceeds many existing methods.

Scene text detection is a task that detects the position of text in natural scenes. Due to the different sizes, arbitrary orientations, different colors of texts, as well as low contrast and resolution in the complex background, text detection in natural scene images is very challenging. So far, the detection results for text instances in motion blur, low-resolution images are still not satisfactory. In this paper, in order to solve the above problems, we propose an effective and robust text detection network that combines a state-of-the-art contrastive learning method SimCLR. Before being input to the feature extractor, the data is augmented in different methods, and then we calculate the similarity of the extracted corresponding feature pairs. This can significantly improve the performance of the detector in difficult conditions. We conduct a series of experiments on the public dataset ICDAR2013, ICDAR2015 and MSRA-TD500. On the ICDAR 2015 dataset, our method achieves F-measure of 0.840 and runs at 9.1 FPS at 720p resolution, demonstrating that the proposed method is effective and efficient.

The nonzero interlayer Schottky barrier leads to a compromise between photodetectivity and photoresponsivity in photodiodes based on vdW heterojunctions. Seeking for the appropriate vdW heterojunction with Ohmic contact and a high tunneling barrier is of great significance to realize high-performance photodiodes. We built borophene/C4N4 (B/C4N4) vdW heterojunctions with a reduced interlayer Schottky barrier, by combining density functional theory and non-equilibrium Green's function. The adsorption of Li-ions can further tune its Schottky contact into n-type Ohmic contact. The electronic properties of the Li-ion-adsorbed B/C4N4 vdW heterojunction, including the separation of hole–electron pairs, the work function, as well as the effective mass of carrier, can be modulated by changing the adsorption site of Li-ions. B/C4N4/Li shows the most excellent absorbing capability of the infrared illumination and the strongest negative rectification, due to the highest interlayer tunneling barrier. The bottom surface of the C4N4 sublayer is the optimal adsorption site of Li-ions, for the potential application of B/C4N4 vdW heterojunctions in tunneling photodiodes. Our work unveils the great significance of Li-ion adsorption in modulating the interlayer Schottky and tunneling barriers in vdW heterojunctions, thus improving their device performance.

Li Zhou,1 Wanxin Yang,1 Enping Yao,1 Haiyan Li,2 Jihui Wang,2 Kun Wang,3 Xiaohua Zhong,1 Zhongxing Peng,4 Xuming Huang1 1Department of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, People’s Republic of China; 3School of Health Science, Guangdong Pharmaceutical University, Guangzhou 510310, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaCorrespondence: Xuming HuangDepartment of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaTel +86-20-82804660Email zr0370@163.comZhongxing PengDepartment of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaEmail pliunblgeve68@163.comBackground: Ischemic stroke, which often occurs with high morbidity, disability, and mortality, is a main cause of brain disease. In various types of human diseases, it is found that microRNAs (miRNAs) are considered as gene regulators. Increasing studies have proved that fluctuation of miRNAs, in the pathologies of ischemic stroke, plays a vital role. However, the accurate regulatory mechanism of cerebral ischemic stroke by miRNAs is still unclear. In this research, we investigated the inhibition mechanism of miR-488-3p on neuronal death through targeting vacuolar protein sorting 4B (VPS4B) in cerebral ischemia/reperfusion (I/R) injury.Methods: Western blot and qRT-PCR were utilized to detect the miR-488-3p level and VPS4B expression. The cell counting kit-8 (CCK-8) assay was utilized to measure the function of miR-488-3p in cell death induced by oxygen glucose deprivation/reoxygenation (OGD/R). After middle cerebral artery occlusion/reperfusion (MCAO/R), the impact of miR-488-3p on infarct volume in mouse brain was assessed. The targets of miR-488-3p were confirmed by luciferase analysis and bioinformatics software.Results: The miR-488-3p level remarkably reduced in primary neuronal cells administrated with OGD/R. Similarly, it also decreased in the mouse brain administrated with MCAO/R. Additionally, the up-regulation of miR-488-3p expression suppressed the death of neuronal cells and restrained ischemic brain infarction in ischemia-stroked mice. Besides, the results showed that VPS4B, which could be inhibited by miR-488-3p, was a direct target of miR-488-3p. This research revealed that the inhibition of VPS4B protected the neuronal cells in ischemic stroke both in vitro as well as in vivo. Meanwhile, this inhibition strengthened positive impact generated by miR-488-3p on ischemic injury.Conclusion: Overall, miR-488-3p played a critical role on neuroprotective function via reducing VPS4B protein level. These results performed a new underlying curative target for the treatment of cerebral ischemic stroke.Keywords: miR-488-3p, VPS4B, ischemia/reperfusion, I/R, ischemic stroke

Pregnant women are often excluded from routine clinical trials. Consequently, appropriate dosing regimens for majority of drugs are unknown in this population, which may lead to unexpected safety issue or insufficient efficacy in this un-studied population. Establishing evidence through the conduct of clinical studies in pregnancy is still a challenge. In recent decades, physiologically-based pharmacokinetic (PBPK) modeling has proven to be useful to support dose selection under various clinical scenarios, such as renal and/or liver impairment, drug-drug interactions, and extrapolation from adult to children. By integrating gestational-dependent physiological characteristics and drug-specific information, PBPK models can be used to predict PK during pregnancy. Population pharmacokinetic (PopPK) modeling approach also could complement pregnancy clinical studies by its ability to analyze sparse sampling data. In the past five years, PBPK and PopPK approaches for pregnancy have made significant progress. We reviewed recent progress, challenges and potential solutions for the application of PBPK, PopPK, and exposure-response analysis in clinical drug development for pregnancy.

Semiconductor photocatalysis technology, which can kill pathogenic microorganisms in a green and broad-spectrum way, is a new research field with great application potential. Due to the dependence on light, semiconductor materials have the problems of low utilization rate of sunlight and inactivation under dark conditions. A simple Au-loaded g-C3 N4 (Au/g-C3 N4 ) nanocomposites was studied. Under dark conditions, the antibacterial efficiency of 1.2 % Au/g-C3 N4 reached 99.1 % relative to 105 CFU (Colony-FormingUnits)/mL E. coli. Under light conditions, the antibacterial efficiency of 0.9 % Au/g-C3 N4 reached 94.1 % relative to 107 CFU/mL E. coli. The influence of contact time, Au loading and bacterial concentration on its antibacterial performance under dark conditions was discussed in detail. Through photoelectrochemistry, SEM, TEM and reactive oxygen species (ROS) detection the microscopic charge behaviour was revealed in the system, and a light-dark dual-mode antibacterial mechanism was proposed.

Aims Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure–efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. Subject and methods In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications. Results A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h−1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml). Conclusion Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics–pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.

Background Cystic adenomyosis is a particular type of adenomyosis, High intensity focused ultrasound (HIFU), as a non-invasive method, has also been used to treat adenomyosis. The purpose of this study was to investigate the efficacy, safety, and feasibility of HIFU for the treatment of cystic adenomyosis. Methods Diagnosis of cystic adenomyosis was obtained through trans-vaginal ultrasound and magnetic resonance imaging (MRI). Ultrasound-guided HIFU ablation was performed under conscious sedation. The patients were evaluated by the comparison of pre-HIFU and post-HIFU imaging, as well as the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire subscales, consisting of Symptom Severity Score (SSS) and Heath Related Quality of Life (HRQL). Results HIFU was effective in treating cystic adenomyosis. No complications were observed in the four patients who were successfully treated with HIFU. Compared to preoperative symptoms and patient satisfaction, symptoms at the first follow-up observed significant improvements, with no dysmenorrhea and high health-related quality of life. During the outpatient follow-up of one month, three months, and six months postoperation, the four patients were still without dysmenorrhea and were highly satisfied with the HIFU ablation. Conclusions HIFU, as a non-invasive treatment, supplies a safe and effective possibility for the treatment of cystic adenomyosis.

OBJECTIVE The aim of the study was to investigate the morphological and functional changes of the tibialis anterior muscle after mirror visual feedback combined with electromyographic biofeedback in poststroke patients. DESIGN A total of 46 poststroke patients were randomly divided into three groups: a mirror visual feedback + electromyographic biofeedback group, a mirror visual feedback group, and a control group. The mirror visual feedback + electromyographic biofeedback group was treated with both mirror visual feedback and electromyographic biofeedback, and the mirror visual feedback group was treated with mirror visual feedback alone. The morphological parameters, including the pennation angle, muscle thickness, and fascicle length, were assessed. RESULTS After 4 wks of treatment, the pennation angle and muscle thickness values were significantly increased in the mirror visual feedback + electromyographic biofeedback and mirror visual feedback groups (P < 0.05). The increase of these values in the mirror visual feedback + electromyographic biofeedback group was significantly greater than that in both metrics in the mirror visual feedback and control groups (P < 0.05), and those in the mirror visual feedback group were greater than those in the control group (P < 0.05). There was no significant difference in the fascicle length value among the three groups as a result of the treatment. After the treatment, the neurological functions were all increased in three groups (P < 0.05). CONCLUSIONS A combination of mirror visual feedback and electromyographic biofeedback seems to be an effective therapy for improving the motor function of the tibialis anterior muscle in poststroke patients.Clinical trial registration number: ChiCTR1800017050.

This study evaluated the removal of multiple pollutants, i.e., polybrominated diphenyl ethers (PBDEs), novel halogenated flame retardants (HFRs), sulfonamide antibiotics (SAs), and heavy metals (HMs), by a full-scale reversed A2/O process in a sewage treatment plant (STP) in Guangzhou, China. The reversed A2/O process demonstrated high removal efficiencies (REs) for total PBDEs (60.5% ± 4.3%), novel HFRs (98.4% ± 2.8%) and HMs (70.1% ± 1.2%), and a relatively low RE for SAs (25.0% ± 2.3%). BDE 209, the dominant PBDE congener, showed a high residual concentration (13.41 ± 5.18 ng/L) in the suspended particulate matter (SPM) of treated effluents. Some novel HFRs, dechlorane plus (DP) and decabromodiphenyl ethane (DBDPE), were detected in the SPM of the raw sewage (7.50 ± 4.14 ng/L and 11.52 ± 11.65 ng/L, respectively). The removal of SAs was mainly through biodegradation in the activated sludge bioreactors (ASBs). Of the HMs, Mn and Ni exhibited the lowest REs (47.5% ± 2.2% and 35.0% ± 2.6%, respectively), while Cr and Cu showed the highest removal (REs > 80%). In terms of treatment units in the reversed A2/O process, ASBs showed the highest RE (27.8%) for the multiple pollutants. The information can aid in our understanding of removal properties of STPs on various pollutants and evaluating the ecological/health risks of STPs as point pollutant sources

Oxygen supply for ischemic brain tissue during stroke is critical to neuroprotection. Remote ischemic conditioning (RIC) treatment is effective for stroke. However, it is not known whether RIC can improve brain tissue oxygen supply. In current study, we employed a mouse model of stroke created by middle cerebral artery occlusion (MCAO) to investigate the effect of RIC on oxygen supply to the ischemic brain tissue using a hypoxyprobe system. Erythrocyte oxygen-carrying capacity and tissue oxygen exchange were assessed by measuring oxygenated hemoglobin and oxygen dissociation curve. We found that RIC significantly mitigated hypoxic signals and decreased neural cell death, thereby preserving neurological functions. The tissue oxygen exchange was markedly enhanced, along with the elevated hemoglobin P50 and right-shifted oxygen dissociation curve. Intriguingly, RIC markedly elevated 2,3-biphosphoglycerate (2,3-BPG) levels in erythrocyte, and the erythrocyte 2,3-BPG levels were highly negatively correlated with the hypoxia in the ischemic brain tissue. Further, adoptive transfusion of 2,3-BPG-rich erythrocytes prepared from RIC-treated mice significantly enhanced the oxygen supply to the ischemic tissue in MCAO mouse model. Collectively, RIC protects against ischemic stroke through improving oxygen supply to the ischemic brain tissue where the enhanced tissue oxygen delivery and exchange by RIC-induced 2,3-BPG-rich erythrocytes may play a role.

To address the energy and environmental issues related to the use of traditional fossil fuels, the thermal utilization of low-grade solid fuels such as low-rank coal, biomass, and municipal solid w...

This phase 1, open‐label, single‐center study evaluated the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of single‐dose emicizumab in healthy Chinese males. Overall, 16 subjects received a single subcutaneous dose of 1‐mg/kg emicizumab. Blood samples were obtained before dosing on day 1 and at regular intervals over 16 weeks after dosing for PK evaluation. A single 1‐mg/kg subcutaneous dose of emicizumab was safe and well tolerated in healthy Chinese male subjects in the study. Mean (± standard deviation) area under the concentration‐time curve from time 0 to infinity and maximum concentration were 287 ± 74.2 μg⋅d/mL and 7.11 ± 1.77 μg/mL, respectively, with a terminal half‐life of 26.7 (±4.3) days. Emicizumab administration did not show significant impact on pharmacodynamic markers tested, which mostly remained stable throughout the study. One subject tested positive for antidrug antibody, with no impact on his PK or safety profile. Compared with results from healthy Japanese and Caucasian subjects receiving the same dose in previous clinical trials, the current results further indicated the absence of difference of emicizumab PK profile across Chinese, Japanese, and Caucasian subjects, validating the use of similar therapeutic doses in Asian and non‐Asian populations.

Background and Objective Dabigatran etexilate is a non-vitamin K antagonist oral anticoagulant (NOAC) that is used to prevent stroke and systemic embolism in adults with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. Pharmacokinetic data on this anticoagulant in Chinese subjects are limited. This study aimed to provide further information on the pharmacokinetic profile of dabigatran in healthy Chinese subjects, together with its safety profile. Methods This was an open-label, single-centre, phase I study. Subjects were randomized into 110 and 150 mg dabigatran etexilate treatment groups. Each subject received 7 days of treatment: a single dose on day 1, no dose on days 2–3, and then multiple doses on days 4–10. Blood samples were collected to analyze the pharmacokinetic profile of dabigatran. All adverse events (AEs) were recorded. Routine clinical laboratory tests, a physical examination, vital signs, and 12-lead electrocardiogram (ECG) measurements were performed. Results A total of 28 subjects (14 males and 14 females) were randomized in this trial. The plasma concentration of total dabigatran reached its maximum measured concentration at a median time of 3–4 h from the dose of interest (either the initial single dose on day 1 or the final dose on day 10) under fed conditions, and declined with an elimination half-life of 10.7–10.9 h following the dose of interest. There was a modest difference in pharmacokinetic profile between male and female subjects. None of the subjects experienced a serious adverse event (SAE) or an AE of moderate or severe intensity. The investigator reported that 17 of the 28 subjects had mild treatment-emergent AEs that resolved without any concomitant treatment or intervention. No clinically significant changes in vital signs or ECG parameters were observed. Conclusions This study revealed the pharmacokinetic characteristics and good safety profile of dabigatran in healthy Chinese subjects. Electronic supplementary material The online version of this article (10.1007/s13318-020-00626-4) contains supplementary material, which is available to authorized users.

A new nonlinear track-bridge random model was established based on OpenSEES, of which the random seismic responses is systematically studied by using probability density evolution method (PDEM). First, a three-dimensional detail nonlinear random dynamic model of the track-bridge coupled system in high-speed railway is established considering the earthquake as the random excitation. The dynamic model is composed with the rail, CRTS II slab ballastless track, the simple supported bridges, bearing, pier and the pile foundation, from which the random dynamic equation of the random model is formulated. In order to evaluate the seismic performance of track structures from a random perspective, the random seismic responses of high-speed railway bridge under random seismic excitations are investigated and analyzed by using the PDEM. Eventually, the Newmark β integration method and the double edge difference method of TVD format are adopted to obtain the random responses involving the probability functions, which can be translated to get the mean value and the standard deviation of responses. Thus, the abundant probability information of seismic responses of the high-speed railway bridge under random seismic excitations can be obtained. The PDF and CDF of the sliding layer are obtained; thus, the failure probability and reliability of different damage grades of sliding layer are obtained. Discussions and significant conclusions on the random dynamic responses are presented.

Background The epidermal growth factor receptor (EGFR) gene has been identified as the driving gene of non-small cell lung cancer (NSCLC), and EGFR-tyrosine kinase inhibitor (TKI) has shown efficacy, but acquired resistance is inevitable. It has been confirmed that the secondary EGFR Thr790Met (T790M) mutation accounts for about 50% of the mechanisms of acquired resistance to EGFR-TKI. The third-generation of EGFR-TKI has significantly efficacy in advanced T790M-positive NSCLC patients. Therefore, it is necessary to detect the status of T790M in patients with acquired resistance after first generation EGFR-TKI. The objective of this study was to investigate the positive rate of plasma test T790M mutation and its relationship with different clinical characteristics, and the frequency of T790M mutation in advanced EGFR-mutant NSCLC patients with acquired resistance after firstline EGFR-TKI treatment. Methods Patients from a single clinical center (Taizhou hospital) were recruited prospectively from September 2017 to June 2018. The eligibility criteria of the trial included the following: (I) aged 18 years or older, histologically confirmed NSCLC stage IIIB/st and EGFR mutation positive; (II) progressive disease (PD) after first generation EGFR-TKI by RECIST v1.1, with PFS>3 months; (III) no third generation TKI treatment. All patients signed informed consent, had 10 mL of blood drawn, and were evaluated for the presence of T790M gene by amplification refractory mutation system (ARMS). The study was approved by the Ethics Committee of Taizhou Hospital (ethical batch number: 201637). Results A total of 189 patients were included in the analysis. The overall T790M mutation rate of plasma detection was 36.51% (69/189). The positive rate of T790M mutation after the failure of first generation EGFR-TKI treatment was not correlated with the patient's age, sex, and the type of first generation TKI drugs. However, it was related to the mutation type of EGFR in baseline and the mode of progression according to reports by Wu et al. The frequency of T790M mutation among patients with initial exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 45.45%, 26.19% and 33.33%, respectively. The mutation rate of T790M in 19del mutant patients was higher than that of L858R mutation and other mutations (P=0.026). The frequency of T790M mutation in local progression patients was 50% after the first generation TKI was resistant to drug treatment: in gradual progression it was 26.92%, and in dramatic progression it was 38.10%. The frequency of T790M mutation of patients with local progression was significantly higher (P=0.031). Conclusions The patients with EGFR mutations after the first generation of EGFR-TKI-acquired resistance of NSCLC were evaluated for their plasma EGFR mutation status, and the overall T790M mutation rate of was 36.51%. The frequency of T790M mutation with initial mutation of 19 del was higher than that of L858R mutation and other mutations, and local progression was higher than that in patients with gradual progression and dramatic progression.

Purpose The burden of hepatitis C virus infection is particularly high in Asian countries, and new treatments are urgently needed. The purpose of this study was to characterize the pharmacokinetics (PK) and safety of the fixed-dose combination tablet of elbasvir/grazoprevir in healthy Chinese participants. Patient and Methods In this Phase I, single-site, open-label, 3-period study in healthy Chinese adults, participants received a single tablet of elbasvir 50 mg/grazoprevir 100 mg, followed by blood sampling for up to 96 hrs (http://www.chinadrugtrials.org.cn/ CTR20160034; Protocol PN071). Participants then received 1 tablet daily for 10 days, followed by a minimum 10-day washout, after which participants received a single dose of 2 tablets (elbasvir 100 mg/grazoprevir 200 mg). Elbasvir and grazoprevir PK were assessed following single and multiple doses. Safety and tolerability were also evaluated. Results Twelve participants (50% male) were enrolled in and completed the study. Following single-dose oral administration of elbasvir 50 mg/grazoprevir 100 mg or elbasvir 100 mg/grazoprevir 200 mg, the median Tmax was 3-4 hrs and elimination half-life was 18 hrs (elbasvir) and 30 hrs (grazoprevir). Multiple-dose administration resulted in AUC0-24 accumulation ratios of 1.58 (elbasvir) and 2.35 (grazoprevir). Both elbasvir 50 mg/grazoprevir 100 mg and 100 mg/200 mg regimens were generally well tolerated. Conclusion Single-dose administration of elbasvir 50 mg/grazoprevir 100 mg or 100 mg/200 mg and once-daily administration of elbasvir 50 mg/grazoprevir 100 mg for 10 days has been adequately characterized, with PK values within the expected range, and was generally well tolerated in healthy Chinese male and female participants.

To introduce and evaluate current research progress of moxibustion in the prevention and treatment of acute infectious diseases, related literature in CNKI, Wanfang Data, and SinoMed was retrieved and analyzed by the present study. Results showed abundant studies on the mechanism of action of moxibustion in the prevention and treatment of acute infectious diseases with remarkable clinical efficacy. The present study also summarizes the commonly-occurring problems and found out the deficiencies in existing studies in hope of providing more reference for further research.

Designing energy storage systems with both high energy density and power density by using low-cost electrodes is still a formidable challenge. Therefore, we propose a successful doped porous carbon synthesis process using agricultural waste in the form of ginger straw, which can be used for fabricating high-performance supercapacitors and Li-ion capacitors. Nitrogen doping in the carbon structure improves the wettability and alters the electronic structure, playing a pivotal role in providing extra charge storage capacity. The fabricated ionic-liquid-based supercapacitors exhibit an outstanding capacitance of 122 F g−1 at 0.5 A g−1 with a superb capacitance retention ratio of 73% at 100 A g−1, excellent specific energy of 37.8 W h kg−1 at 374 W kg−1, and low capacitance loss of 13.5% after 10 000 cycles. Based on the LiPF6 electrolyte, doped carbon used as the anode shows a high capacity of 1531 mA h g−1 at 0.1 A g−1, and the fabricated Li-ion capacitor exhibits high specific energy of 214.6 W h kg−1 at 373.5 W kg−1, maintains 63.6 W h kg−1 at the high specific power of 65.4 kW kg−1, and shows promising cycling performance with 82.7% capacity retention after 10 000 cycles. This work highlights the fact that sustainably doped carbon has the potential for large-scale commercial production, and it can be promising for use as an electrode in advanced energy storage systems.

Gonadotropin-releasing hormone analog (GnRHa) is the mainstream treatment for central precocious puberty (CPP). However, its effect on the ovarian reserve in CPP girls remains unclear. This study was designed to analyze the changes of ovarian reserve in CPP girls during and after GnRHa therapy, with an attempt to achieve the early prediction of the effect of GnRHa treatment on the reproductive function of CPP girls, eliminate the concerns of girls and their parents on the potential toxicities of GnRHa treatment, and improve the patients' adherence to treatment.The clinical data of 383 CPP girls who had been treated with GnRHa for more than half a year in our hospital within the past 10 years were retrospectively analyzed. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), FSH/LH, estradiol (E2), and anti-Müllerian hormone (AMH) levels, as well as uterine and ovarian volumes, were measured before treatment, at various time points during treatment, and after menarche or resumption of menses (ROM) after treatment discontinuation.GnRHa treatment had similar effects on uterine/ovarian volumes, LH, FSH, and E2: these indicators were significantly inhibited during the treatment (compared with the pre-treatment levels), gradually returned normal after drug withdrawal, and became significantly higher than the pre-treatment levels after menarche or ROM (both P0.05 for LH and FSH levels and P0.05 for E2 and uterine/ovarian volumes). AMH level transiently decreased 6 months after GnRHa treatment (2.70±1.76 vs. 3.56±2.21, t=3.227, P=0.001); however, the AMH levels after 12, 18, and 24 months of treatment were similar to the pre-treatment level (P0.05). The FSH/LH ratio significantly increased after 12 months of treatment compared with the pre-treatment (P0.05), and the FSH/LH ratio after menarche or ROM was significantly lower than the pre-treatment value (1.34±0.66 vs. 5.69± 6.85, t=3.068, P=0.006). When FSH/LH and FSH level were used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was higher than at pre-treatment (FSH/LH ratio: 100% vs. 46%, χ2=27.586, P0.05; FSH level: 100% vs. 99%, P0.05). When AMH level was used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was slightly lower than at pre-treatment (87% vs. 93%, P0.05).The ovarian reserve of CPP girls is somehow inhibited during GnRHa treatment but is gradually restored after drug discontinuation. Thus, GnRHa treatment does not affect ovarian reserve in CPP children after the treatment stops.

Purpose: To evaluate the midterm outcomes of thoracic endovascular aortic repair (TEVAR) using chimney grafts (ch-TEVAR) or thoracic stent-grafts with fenestrations made on the back table (f-TEVAR) to treat thoracic aortic dissection (TAD) and thoracic aortic aneurysm (TAA). Materials and Methods: A retrospective analysis was conducted of 474 consecutive patients (mean age 62.3±10.7 years; 346 men) treated with either f-TEVAR (n=110) or ch-TEVAR (n=364) for 352 TADs (81 f-TEVAR and 271 ch-TEVAR) or 122 TAAs (29 f-TEVAR and 93 ch-TEVAR) from 2008 to 2016. The primary endpoints at 30 days and during follow-up were overall mortality, aorta-related mortality, and major complications. The secondary endpoints were endoleak and reintervention. The patency of the target branches, cost of hospitalization, and the use of antiplatelet drugs were also analyzed. Results: Intraoperative type I endoleaks were treated in 69 (14.6%) cases (4 f-TEVAR and 65 ch-TEVAR, p

As a functional monosaccharide, L-arabinose has protective effects on metabolic syndrome, but whether it is effective for cerebral ischemia in diabetic patients remains unknown. The middle cerebral artery occlusion (MCAO) model of type 2 diabetic rats was prepared and applied to determine the effect of L-arabinose on cerebral infarction (CI) with or without diabetes. Results showed that diabetes aggravated neurological deficits, increased the volume of CI, brain edema, and blood–brain barrier (BBB) permeability after CI, which were alleviated by L-arabinose by repairing the damaged tight-junction proteins (zonula occludens 1 and claudin-5). L-arabinose could reverse the expression of nuclear factor-κB (NF-κB) p65, intercellular cell adhesion molecule-1, and tumor necrosis factor α in the MCAO model with diabetes. Conclusions: L-arabinose alleviates diabetes-aggravated cerebral ischemic injury by alleviating the destruction of the BBB via the downregulation of the NF-κB signaling pathway.

Background PB-201, a partial, pancreas/liver-dual glucokinase activator, showed good tolerance and glycaemic effects in multinational studies. This study determined its optimal dose, safety, pharmacokinetics, and pharmacodynamics in Chinese patients with type 2 diabetes. Methods In this double-blind, randomised, four-period, crossover, phase 1 trial in China, conducted at the Peking University Third Hospital, adult patients with drug-naive type 2 diabetes were randomised (1:1:1:1) to four sequence groups using a computer-generated randomisation table. In each period, they received oral placebo or PB-201 (50+50, 100+50, or 100+100 mg split doses) for 7 days. Investigators and patients were masked to treatment assignment. The primary endpoints were safety and pharmacokinetics. Continuous glucose monitoring was used to delineate the glucose excursion profile. Trial registration number: NCT03973515. Findings Between August 27, 2019 and December 19, 2019, 16 patients were randomised. PB-201 showed a dose-proportional pharmacokinetic profile without apparent accumulation in the body and induced dose-dependent lowering of blood glucose. PB-201 at 50+50, 100+50, and 100+100 mg increased mean time in range (49·210% [standard deviation 27], 56·130% [25], and 63·330% [20] with three doses, respectively) versus placebo (49·380% [27]) and reduced estimated glycated haemoglobin from baseline (-0·5445% [1·654], -1·063% [1·236], and -1·888% [1·381] vs -0·581% [1·200]). Fifteen patients (93·8%) had treatment-emergent adverse events, which were mild. No patients had hypoglycaemia with venous/capillary glucose

Background Ureaplasma urealyticum (UU) is found among the normal vaginal flora in a considerable proportion of asymptomatic women; however, adult central nervous system (CNS) infection of UU is extremely rare. Good's syndrome (GS) is an adult-onset immunodeficiency characterized by thymoma, hypogammaglobulinaemia, low or absent B‑cells, and an inverted CD4+/CD8+ T‑cell ratio. Patients with GS usually have severe or recurrent infections. Case presentation We describe the case report of a 49-year-old woman who developed UU meningitis. Initial routine anti-viral and anti-bacterial therapy showed no improvement in the patient's condition. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) identified the UU DNA sequence. Accordingly, a diagnosis of UU meningitis was made, and minocycline therapy was initiated. The patient responded favourably, with no signs of disease at subsequent follow-up. According to the severity and rarity of the case, secondary immunodeficiency was suspected. Flow cytometry found hypogammaglobulinaemia. Combined with the previous history of thymoma, the patient was diagnosed with immune deficiency disease of GS. Conclusions This case may be the first adult case report in the literature describing UU meningitis in a patient with GS. The diagnosis of GS should be considered in patients presenting with unexplained antibody deficiency and thymoma.

Cardiac hypertrophy, acting as a pathologic progress of chronic hypertension and coronary disease. Increasing evidence indicates that lncRNA potassium voltage-gated channel subfamily q member 1 overlapping transcript 1 (KCNQ1OT1) may led to MI. Recent studies showed, miR-301b level was evidently decreased in heart failure patients. To explore the regulate effect of lncRNAKCNQ1OT1 and miR-301b in cardiac hypertrophy, gain-and-lose function assays were tested. Notably, lncRNAKCNQ1OT1 overexpression causes a significant result as cardiac hypertrophy. Furthermore, lncRNAKCNQ1OT1 sponge microRNA-301b. The results showed that miR-301b exhibited lower expression in cardiac hypertrophy model, indicating that it may exert anti-hypertrophic role. Furthermore, the BNP and β-MHC expression increased, as well as cardiomyocyte surface area, with Ang II treatment, while the effect was repealed by miR-301b. Moreover, the protein expression of Tcf7 was down-regulated or up-regulated by miR-301b or AMO-301b. As displayed by luciferase reporter assay, miR-301b binds to 3’UTR of Tcf7. Briefly, we aimed to elucidate a down-regulate role of miR-301b in cardiac hypertrophy, as to provide potential therapeutic strategies.

Objective: The purpose of this study was to explore the level of coronavirus disease 2019 (COVID-19) vaccine hesitancy among medical students in Wuhan, China, and to identify the factors and barriers associated with their vaccination decision. Methods: A cross-sectional survey was launched with 612 medical students recruited by convenience sampling from 6 universities. Data collection measures mainly included a demographic questionnaire, COVID-19 vaccine knowledge questionnaire, and the vaccine hesitancy scale. Results: A total of 58.2% of medical students reported vaccine hesitancy. The most common reasons for this were worrying about the side effects of vaccines (44.4%), uncertainty about vaccine safety (40.4%), and underestimating the risk of exposure to COVID-19 (27.9%). The main factors associated with COVID-19 vaccine hesitancy among participants were their knowledge about COVID-19 vaccine, training related to COVID-19 vaccines, family address, and education level (P < 0.05). Conclusions: The government, health department and universities in China need to work together and actively communicate with vaccine-hesitant students, establish a standardized COVID-19 vaccine course, and provide on-campus vaccination services.

ObjectsImigliptin is a novel dipeptidyl peptidase-4 inhibitor. In the present study, we aimed to evaluate the effects of imigliptin and alogliptin on insulin resistance and beta-cell function in Chinese patients with type-2 diabetes mellitus (T2DM).MethodsA total of 37 Chinese T2DM patients were randomized to receive 25 mg imigliptin, 50 mg imigliptin, placebo, and 25 mg alogliptin (positive drug) for 13 days. Oral glucose tolerance tests were conducted at baseline and on day 13, followed by the oral minimal model (OMM).ResultsImigliptin or alogliptin treatment, compared with their baseline or placebo, was associated with higher beta-cell function parameters (φs and φtot) and lower glucose area under the curve (AUC) and postprandial glucose levels. The changes in the AUC for the glucose appearance rate between 0 and 120 min also showed a decrease in imigliptin or alogliptin groups. However, the insulin resistance parameter, fasting glucose, was not changed. For the homeostatic model assessment (HOMA-β and HOMA-IR) parameters or secretory units of islets in transplantation index (SUIT), no statistically significant changes were found both within treatments and between treatments.ConclusionsAfter 13 days of treatment, imigliptin and alogliptin could decrease glycemic levels by improving beta-cell function. By comparing OMM with HOMA or SUIT results, glucose stimulation might be more sensitive for detecting changes in beta-cell function.

Objective. This review aimed at systematically evaluating the efficacy and safety of moxibustion for chronic fatigue syndrome (CFS). Methods. Relevant trials were searched in seven digital databases up to January 2021. After literature screening, data extraction, and literature quality evaluation, the included studies were meta-analyzed using RevMan 5.4 software. The evidence level was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results. Fifteen studies involving 1030 CFS participants were included. Meta-analyses showed a favorable effect of moxibustion on the total effective rate compared with acupuncture (OR = 4.58, 95%CI = [2.85, 7.35], P < 0.00001 ) and drugs (OR = 6.36, 95%CI = [3.48, 11.59], P < 0.00001 ). Moxibustion also appeared to significantly reduce fatigue severity measured by fatigue scale-14 (FS-14) (WMD = −2.20, 95% CI = [−3.16, −1.24], P < 0.00001 ) and fatigue assessment instrument (FAI) (WMD = −16.36, 95% CI = [−26.58, −6.14], P = 0.002 ) compared with the control group. In addition, among the 15 included studies, only two studies reported adverse events related to moxibustion, and the symptoms were relatively mild. The quality of evidence based on the 15 included trials was assessed as moderate to very low. Conclusions. Based on limited evidence, moxibustion might be an effective and safe complementary therapy for CFS, which can be recommended to manage CFS. Because of the limited level of evidence in this review, further high-quality trials are still needed to confirm these findings.