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Background: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials., Objective: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis., Methods: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale., Results: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events., Conclusions: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021)., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Heart sound analysis plays an important role in early detecting heart disease. However, manual detection requires doctors with extensive clinical experience, which increases uncertainty for the task, especially in medically underdeveloped areas. This paper proposes a robust neural network structure with an improved attention module for automatic classification of heart sound wave. In the preprocessing stage, noise removal with Butterworth bandpass filter is first adopted, and then heart sound recordings are converted into time-frequency spectrum by short-time Fourier transform (STFT). The model is driven by STFT spectrum. It automatically extracts features through four down sample blocks with different filters. Subsequently, an improved attention module based on Squeeze-and-Excitation module and coordinate attention module is developed for feature fusion. Finally, the neural network will give a category for heart sound waves based on the learned features. The global average pooling layer is adopted for reducing the model's weight and avoiding overfitting, while focal loss is further introduced as the loss function to minimize the data imbalance problem. Validation experiments have been conducted on two publicly available datasets, and the results well demonstrate the effectiveness and advantages of our method.

Background: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results., Methods: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature., Results: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model., Conclusions: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention., (© 2024. The Author(s).)

Background: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years., Methods: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness., Results: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit., Conclusion: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone., (© 2024. The Author(s).)

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P 4 Mo 6 O 31 } 12- -based compounds, [H 4 (HPTTP)] 2 {Cu I [Mo 12 O 24 (OH) 6 (PO 4 ) 3 (HPO 4 )(H 2 PO 4 ) 4 ]}· x H 2 O ( x = 13 for ( 1 ), 7 for ( 2 ); HPTTP = 4,4',4″,4‴-(1 H -pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1 - 2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.

Background: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca 2+ -dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca 2+ /glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs., Aim: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR., Methods: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis., Results: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca 2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group., Conclusion: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In recent years, the growing pervasiveness of wearable technology has created new opportunities for medical and emergency rescue operations to protect users' health and safety, such as cost-effective medical solutions, more convenient healthcare and quick hospital treatments, which make it easier for the Internet of Medical Things (IoMT) to evolve. The study first presents an overview of the IoMT before introducing the IoMT architecture. Later, it portrays an overview of the core technologies of the IoMT, including cloud computing, big data and artificial intelligence, and it elucidates their utilization within the healthcare system. Further, several emerging challenges, such as cost-effectiveness, security, privacy, accuracy and power consumption, are discussed, and potential solutions for these challenges are also suggested.

Background: The purpose of this study was to explore the relationship between quantitative epicardial adipose tissue (EAT) based on coronary computed tomography angiography (CCTA) and coronary slow flow (CSF)., Methods: A total of 85 patients with < 40% coronary stenosis on diagnostic coronary angiography were included in this retrospective study between January 2020 and December 2021. A semi-automatic method was developed for EAT quantification on CCTA images. According to the thrombolysis in myocardial infarction flow grade, the patients were divided into CSF group (n = 39) and normal coronary flow group (n = 46). Multivariate logistic regression was used to explore the relationship between EAT and CSF. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of EAT in CSF., Results: EAT volume in the CSF group was significantly higher than that of the normal coronary flow group (128.83± 21.59 mL vs. 101.87± 18.56 mL, P < 0.001). There was no significant difference in epicardial fat attenuation index between the two groups (P > 0.05). Multivariate logistic regression analysis showed that EAT volume was independently related to CSF [odds ratio (OR) = 4.82, 95% confidence interval (CI): 3.06-7.27, P < 0.001]. The area under ROC curve for EAT volume in identifying CSF was 0.86 (95% CI: 0.77-0.95). The optimal cutoff value of 118.46 mL yielded a sensitivity of 0.80 and a specificity of 0.94., Conclusions: Increased EAT volume based on CCTA is strongly associated with CSF. This preliminary finding paves the way for future and larger studies aimed to definitively recognize the diagnostic value of EAT in CSF., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Studies on coronary slow flow are receiving increasing attention, but objective evaluations are still lacking. The purpose of this study was to visualize the current status and research hotspots of coronary slow flow through bibliometric analysis., Methods: All relevant publications on coronary slow flow from 2003 to 2022 were extracted from the Web of Science Core Collection database and analyzed by VOSviewer and CiteSpace visualization software. Year of publication, journal, country/region, institution, and first author of each paper, as well as research hotspots were identified., Results: A total of 913 publications were retrieved. The journal with the most publications was Coronary Artery Disease. The country/region with the most publications was Turkey, followed by China and the United States. The institution with the largest publication volume was Turkey Specialized Higher Education Research Hospital. The author with the largest publication volume was Chun-Yan Ma from China. Keyword analysis indicated that "treatment and prognosis", "pathogenesis and risk factors" and "diagnosis" were the clustering centers of coronary slow flow, and the research hotspots gradually changed with time, from pathogenesis to treatment and prognosis., Conclusion: Future research will focus on the search for effective and non-invasive detection indicators and treatments of coronary slow flow. Collaboration needs to be enhanced between different institutions or countries/regions, which would improve clinical outcomes for patients with coronary slow flow., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Image segmentation is a challenging problem in imaging informatics, which stems from the intersection of imaging techniques, computer science and biomedicine. In particular, accurate segmentation of cardiac structures in late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is of great clinical importance for cardiac function assessment and myocardial disease diagnosis. However, it is a well-known challenge due to its special imaging modality and the lack of labeled LGE samples. In this paper, we propose an unsupervised ventricular segmentation algorithm that can perform biventricular segmentation of LGE images in the absence of labeled LGE data. There are two primary modules, the data augmentation procedure and the segmentation network. The easily available annotated balanced-Steady State Free Precession (bSSFP) images are employed for cross-modal data augmentation by image translation, where a single bSSFP image is converted into multiple synthetic LGE images while preserving the original morphological structure. Then, the proposed segmentation network is trained with the synthetic LGE images and used for segmenting real LGE images. Validation experiments demonstrated the effectiveness and advantages of the proposed algorithm.

Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1-3, total N = 366) and two fMRI (Datasets 4-5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

To assess the performance of biplane area-length method in measuring left atrial (LA) volume and sphericity index and to investigate the correlation of LA reservoir function and sphericity index with atrial fibrosis on cardiac magnetic resonance imaging (MRI) in patients with mitral valve disease (MVD). Forty-eight patients with MVD undergoing cardiac MRI scan were enrolled in this retrospective study. LA reservoir function, measured as maximum volume (LAV max ), minimum volume (LAV min ) and ejection fraction (LAEF), and sphericity index were quantified using the biplane area-length method and standard short-axis approach, respectively. Comparisons of LA reservoir function and sphericity index between the two different methods were performed, as well as between positive (n = 17, 35%) and negative atrial wall fibrosis groups (n = 31, 65%). There was no difference in the values of LAV max index and sphericity index between the two different methods. The biplane area-length method had poor performance in assessing LAV min index and LAEF compared to standard short-axis approach, with an underestimation of 13.5% for LAV min index and an overestimation of 27% for LAEF. Patients with positive atrial fibrosis had larger LAV max index, LAV min index and sphericity index, and lower LAEF levels in comparison to the negative atrial fibrosis group. The biplane area-length method has good performance in assessing LA sphericity index for patients with MVD, not in LA reservoir function. Patients with positive atrial fibrosis tend to suffer from more adverse LA remodelling., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Previous assessments of the effectiveness of protected areas (PAs) focused primarily on changes in human pressure over time and did not consider the different human-pressure baselines of PAs, thereby potentially over- or underestimating PA effectiveness. We developed a framework that considers both human-pressure baseline and change in human pressure over time and assessed the effectiveness of 338 PAs in China from 2010 to 2020. The initial state of human pressure on PAs was taken as the baseline, and changes in human pressure index (HPI) were further analyzed under different baselines. We used the random forest models to identify the management measures that most improved effectiveness in resisting human pressure for the PAs with different baselines. Finally, the relationships between the changes in the HPI and the changes in natural ecosystems in PAs were analyzed with different baselines. Of PAs with low HPI baselines, medium HPI baselines, and high HPI baselines, 76.92% (n=150), 11.11% (n=12), and 22.86% (n=8) , respectively, showed positive effects in resisting human pressure. Overall, ignoring human-pressure baselines somewhat underestimated the positive effects of PAs, especially for those with low initial human pressure. For PAs with different initial human pressures, different management measures should be taken to improve effectiveness and reduce threats to natural ecosystems. We believe our framework is useful for assessing the effectiveness of PAs globally, and we recommend it be included in the Convention on Biological Diversity Post-2020 Strategy., (© 2022 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Treating and preventing chronic pain require our understanding of how it develops and maintains. Löffler et al. (2022) 1 demonstrate that distinct operant learning signals in the vmPFC-NAc pathway predict the development and maintenance of chronic back pain., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The ideal treatment strategy for stable three-vessel coronary artery disease (CAD) patients are difficult to determine and for patients undergoing conservative treatment, imaging evidence of coronary atherosclerotic severity progression remains limited. Epicardial fat volume (EFV) on coronary CT angiography (CCTA) has been considered to be associated with coronary atherosclerosis. Therefore, this study aims to evaluate the relationship between EFV level and coronary atherosclerosis severity in three-vessel CAD., Methods: This retrospective study enrolled 252 consecutive patients with three-vessel CAD and 252 normal control group participants who underwent CCTA between January 2018 and December 2019. A semi-automatic method was developed for EFV quantification on CCTA images, standardized by body surface area. Coronary atherosclerosis severity was evaluated and scored by the number of coronary arteries with ≥ 50% stenosis on coronary angiography. Patients were subdivided into groups on the basis of lesion severity: mild (score = 3 vessels, n = 85), moderate (3.5 vessels ≤ score < 4 vessels, n = 82), and severe (4 vessels ≤ score ≤ 7 vessels, n = 85). The independent sample t-test, analysis of variance, and logistic regression analysis were used to evaluate the associations between EFV level and severity of coronary atherosclerosis., Results: Compared with normal controls, three-vessel CAD patients had significantly higher EFV level (65 ± 22 mL/m 2 vs. 48 ± 19 mL/m 2 ; P < 0.001). In patients with three-vessel CAD, there was a progressive decline in EFV level as the score of coronary atherosclerosis severity increased, especially in those patients with a body mass index (BMI) ≥ 25 kg/m 2 (75 ± 21 mL/m 2 vs. 72 ± 22 mL/m 2 vs. 62 ± 17 mL/m 2 ; P < 0.05). Multivariable regression analysis showed that both BMI (OR 3.40, 95% CI 2.00-5.78, P < 0.001) and the score of coronary atherosclerosis severity (OR 0.49, 95% CI 0.26-0.93, P < 0.05) were independently related to the change of EFV level., Conclusion: Three-vessel CAD patients do have higher EFV level than the normal controls. While, there may be an inverse relationship between EFV level and the severity of coronary atherosclerosis in patients with three-vessel CAD., (© 2022. The Author(s).)

As non-pharmaceutical interventions, non-invasive electrical neuromodulation techniques are promising in pain management. With many advantages, such as low costs, high usability, and non-invasiveness, they have been exploited to treat multiple types of clinical pain. Proper use of these techniques requires a comprehensive understanding of how they work. In this article, we reviewed recent studies concerning non-invasive electrical peripheral nerve stimulation (transcutaneous electrical nerve stimulation and transcutaneous vagus/vagal nerve stimulation) as well as electrical central nerve stimulation (transcranial direct current stimulation and transcranial alternating current stimulation). Specifically, we discussed their analgesic effects on acute and chronic pain, and the neural mechanisms thereof. We then contrasted the four kinds of nerve stimulation techniques, pointing out limitations of existing studies and proposing directions for future research. With more extensive and in-depth research to overcome these limitations, we shall witness more clinical applications of non-invasive electrical nerve stimulations to alleviate patients' pain and ease the crippling medical and economic burden imposed on patients, their families, and the entire society.

Background: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients., Case Presentation: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration., Conclusion: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.

Methamphetamine abuse has become a serious public health problem. However, effective treatment for methamphetamine addiction remains elusive, especially considering its high rate of relapse after treatment. A conditioned stimulus (CS) memory retrieval-extinction procedure has been demonstrated to decrease reinstatement of cocaine, heroin, and alcohol seeking in rats, and to reduce cue-induced cravings in heroin and nicotine addicts. The goal of the present study is to explore the effect of the CS memory retrieval-extinction procedure on methamphetamine seeking in rats and the underlying mechanisms. We found that daily retrieval of methamphetamine-associated memories 1 h before extinction sessions decreased subsequent drug priming-induced reinstatement, spontaneous recovery, and renewal of methamphetamine seeking. We also found that retrieval of methamphetamine-associated memories induced neuronal activation in the basolateral amygdala (BLA), while presenting extinction within the time window of reconsolidation abolished the neuronal activation in BLA. These results indicate that the CS memory retrieval-extinction procedure could prevent reconsolidation of methamphetamine memory traces in BLA and subsequent methamphetamine craving and relapse.

Background: Over the years, mesenchymal stromal (stem) cells (MSCs) have been pre-clinically applied in the treatment of variety kinds of diseases including asthma and chronic lung diseases. Aim of the current study was to systematically review and to conduct meta-analysis on the published studies of MSC treatment in asthma animal models., Methods: Publications on the MSC and asthma treatment was thoroughly searched in the electronic databases. Statistical analysis was then performed using the Comprehensive Meta-Analysis software (Version 3). Effect of MSC therapy on asthma model was assessed by Hedges's g with 95% confidence intervals (95% CIs). Random effect model was used due to the heterogeneity between the studies., Results: Meta-analysis of the 32 included studies showed that MSC transplantation was significantly in favor of attenuating lung injury and remodeling (Hedges's g = -9.104 ± 0.951 with 95% CI: -10.969 ∼ -7.240, P < 0.001) and airway inflammation (Hedges's g = -4.146 ± 0.688 with 95% CI: -5.495 ∼ -2.797, P < 0.001). The mechanism of MSC therapy in asthma seems to be regulating the balance of Th1 cytokine and Th2 cytokines (IFN-γ: Hedges's g = 4.779 ± 1.408 with 95% CI: 1.099-2.725, P < 0.001; IL-4: Hedges's g = -10.781 ± 1.062 with 95% CI: -12.863 ∼ -8.699, P < 0.001; IL-5: Hedges's g = -10.537 ± 1.269 with 95% CI: -13.025 ∼ -8.050, P < 0.001; IL-13: Hedges's g = -6.773 ± 0.788 with 95% CI: -8.318 ∼ -5.229, P < 0.001)., Conclusion: Findings of the current systemic review suggested a potential role for MSCs in asthma treatment although it is still challenging in clinical practice. The mechanisms of MSCs in pre-clinical asthma treatment may be associated with attenuating airway inflammation through regulating Th1 and Th2 cytokines., (Copyright © 2018. Published by Elsevier Ltd.)

Posttraumatic stress disorder (PTSD) is an anxiety disorder characterized by intrusive recollections of a severe traumatic event and hyperarousal following exposure to the event. Human and animal studies have shown that the change of amygdala activity after traumatic stress may contribute to occurrences of some symptoms or behaviors of the patients or animals with PTSD. However, it is still unknown how the neuronal activation of different sub-regions in amygdala changes during the development of PTSD. In the present study, we used single prolonged stress (SPS) procedure to obtain the animal model of PTSD, and found that 1 day after SPS, there were normal anxiety behavior and extinction of fear memory in rats which were accompanied by a reduced proportion of activated glutamatergic neurons and increased proportion of activated GABAergic neurons in basolateral amygdala (BLA). About 10 days after SPS, we observed enhanced anxiety and impaired extinction of fear memory with increased activated both glutamatergic and GABAergic neurons in BLA and increased activated GABAergic neurons in central amygdala (CeA). These results indicate that during early and late phase after traumatic stress, distinct patterns of activation of glutamatergic neurons and GABAergic neurons are displayed in amygdala, which may be implicated in the development of PTSD.

Background: Nicotine craving and relapse often occurs after reactivation of nicotine reward memories. We recently developed a memory retrieval-reconsolidation interference procedure in which reactivating nicotine reward memories by acute exposure to nicotine (the unconditioned stimulus [UCS]) and then pharmacologically interfering with memory reconsolidation decreased relapse to nicotine seeking in rats and nicotine craving in smokers. Here, we investigated underlying mechanisms., Methods: In the first series of experiments, we trained rats for nicotine-induced conditioned place preference (CPP) or nicotine self-administration and ventricularly microinjected them with the protein synthesis inhibitor anisomycin immediately after UCS-induced memory retrieval. In the second series of experiments, we used tyramide-amplified immunohistochemistry-fluorescence in situ hybridization to examine neural ensembles in the basolateral amygdala (BLA) reactivated by nicotine conditioned stimulus- or UCS-induced memory retrieval. We then used the Daun02 chemogenetic inactivation procedure to selectively inhibit the nicotine UCS-reactivated BLA neuronal ensembles., Results: Ventricular injections of the anisomycin immediately after nicotine UCS memory retrieval inhibited subsequent nicotine CPP and relapse to operant nicotine seeking after short or prolonged abstinence. More important, within BLA, distinct neuronal ensembles encoded pavlovian CPP and operant self-administration reward memories and nicotine (the UCS) injections in the home cage reactivated both neuronal ensembles. Daun02 chemogenetic inactivation of the nicotine-reactivated ensembles inhibited both nicotine CPP and relapse to nicotine seeking., Conclusions: Results demonstrate that the nicotine UCS-induced memory retrieval manipulation reactivates multiple nicotine reward memories that are encoded by distinct BLA neuronal ensembles that play a role in nicotine preference and relapse., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Exposure to drug-paired cues causes drug memories to be in a destabilized state and interfering with memory reconsolidation can inhibit relapse. Calpain, a calcium-dependent neutral cysteine protease, is involved in synaptic plasticity and the formation of long-term fear memory. However, the role of calpain in the reconsolidation of drug reward memory is still unknown. In the present study, using a conditioned place preference (CPP) model, we found that exposure to drug-paired contextual stimuli induced the activation of calpain and decreased the expression of glutamate receptor interacting protein 1 (GRIP1) in the nucleus accumbens (NAc) core, but not shell, of male rats. Infusions of calpain inhibitors in the NAc core immediately after retrieval disrupted the reconsolidation of cocaine/morphine cue memory and blocked retrieval-induced calpain activation and GRIP1 degradation. The suppressive effect of calpain inhibitors on the expression of drug-induced CPP lasted for at least 14 d. The inhibition of calpain without retrieval 6 h after retrieval or after exposure to an unpaired context had no effects on the expression of reward memory. Calpain inhibition after retrieval also decreased cocaine seeking in a self-administration model and this effect did not recover spontaneously after 28 d. Moreover, the knock-down of GRIP1 expression in the NAc core by lentivirus-mediated short-hairpin RNA blocked disruption of the reconsolidation of drug cue memories that was induced by calpain inhibitor treatment. These results suggest that calpain activity in the NAc core is crucial for the reconsolidation of drug reward memory via the regulation of GRIP1 expression. SIGNIFICANCE STATEMENT Calpain plays an important role in synaptic plasticity and long-term memory consolidation, however, its role in the reconsolidation of drug cue memory remains unknown. Using conditioned place preference and self-administration procedures, we found that exposure to drug-paired cues induced the activation of calpain and decreased glutamate receptor interacting protein 1 (GRIP1) expression in the nucleus accumbens (NAc) core. The inhibition of calpain activity in the NAc core immediately after retrieval disrupted the reconsolidation of cocaine/morphine cue memory that was blocked by prior GRIP1 knock-down. Our findings indicate that calpain-GRIP signaling is essential for the restabilization process that is associated with drug cue memory and the inhibition of calpain activity may be a novel strategy for the prevention of drug relapse., (Copyright © 2017 the authors 0270-6474/17/378938-14$15.00/0.)

JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC 50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC 50 of 3.0 and 3.1 nmol/L, respectively. Furthermore, JS-001 displayed distinct species cross-reactivity: it could bind to the PD-1 antigen on the peripheral blood mononuclear cells (PBMCs) of humans and cynomolgus monkeys, but not to those of mice and woodchucks; the K d values for the interaction between JS-001 and PD-1 antigens on CD8 + T cells of human and cynomolgus monkey were 2.1 nmol/L and 1.2 nmol/L, respectively. In vitro, treatment with JS-001 (0.01-10 μg/mL) dose-dependently stimulated human T cell proliferation, as well as IFN-γ and TNF-α secretion. In HBsAg-vaccinated cynomolgus monkeys, the expression of PD-1 + /CD4 + and PD-1 + /CD8 + was significantly elevated, intramuscular injection of JS-001 (1 and 10 mg/kg) resulted in dramatic decreases in PD-1 + /CD4 + and PD-1 + /CD8 + expression in a dose-dependent manner, which was supported by PD-1 receptor occupancy (RO) results. In the PK study, 18 cynomolgus monkeys treated with single, ascending doses of 1, 10, and 75 mg/kg, and another 6 cynomolgus monkeys received 10 mg/kg successive administration. The plasma clearance of JS-001 followed a linear PK profile with single administration in the 1 and 10 mg/kg groups and a non-linear PK profile in the 75 mg/kg group. In the successive 10 mg/kg administration group, no drug accumulation was observed. But the AUC from the last exposure was lower than that of the first administration, which was probably due to the production of ADAs, as demonstrated in immunogenicity study. These non-clinical data are encouraging and provide a basis for the efficacy and safety of JS-001 in clinical trials.

Importance: A relapse into nicotine addiction during abstinence often occurs after the reactivation of nicotine reward memories, either by acute exposure to nicotine (a smoking episode) or by smoking-associated conditioned stimuli (CS). Preclinical studies suggest that drug reward memories can undergo memory reconsolidation after being reactivated, during which they can be weakened or erased by pharmacological or behavioral manipulations. However, translational clinical studies using CS-induced memory retrieval-reconsolidation procedures to decrease drug craving reported inconsistent results., Objective: To develop and test an unconditioned stimulus (UCS)-induced retrieval-reconsolidation procedure to decrease nicotine craving among people who smoke., Design, Setting, and Participants: A translational rat study and human study in an academic outpatient medical center among 96 male smokers (aged 18- 45 years) to determine the association of propranolol administration within the time window of memory reconsolidation (after retrieval of the nicotine-associated memories by nicotine UCS exposure) with relapse to nicotine-conditioned place preference (CPP) and operant nicotine seeking in rats, and measures of preference to nicotine-associated CS and nicotine craving among people who smoke., Intervention: The study rats were injected noncontingently with the UCS (nicotine 0.15 mg/kg, subcutaneous) in their home cage, and the human study participants administered a dose of propranolol (40 mg, per os; Zhongnuo Pharma)., Main Outcomes and Measures: Nicotine CPP and operant nicotine seeking in rats, and preference and craving ratings for newly learned and preexisting real-life nicotine-associated CS among people who smoke., Results: Sixty-nine male smokers completed the experiment and were included for statistical analysis: 24 in the group that received placebo plus 1 hour plus UCS, 23 who received propranolol plus 1 hour plus UCS, and 22 who received UCS plus 6 hours plus propranolol. In rat relapse models, propranolol injections administered immediately after nicotine UCS-induced memory retrieval inhibited subsequent nicotine CPP and operant nicotine seeking after short (CPP, d = 1.72, 95% CI, 0.63-2.77; operant seeking, d = 1.61, 95% CI, 0.59-2.60) or prolonged abstinence (CPP, d = 1.46, 95% CI, 0.42-2.47; operant seeking: d = 1.69, 95% CI, 0.66-2.69), as well as nicotine priming-induced reinstatement of nicotine CPP (d = 1.28, 95% CI, 0.27-2.26) and operant nicotine seeking (d = 1.61, 95% CI, 0.59-2.60) after extinction. Among the smokers, oral propranolol administered prior to nicotine UCS-induced memory retrieval decreased subsequent nicotine preference induced by newly learned nicotine CS (CS1, Cohen d = 0.61, 95% CI, 0.02-1.19 and CS2, d = 0.69, 95% CI, 0.10-1.28, respectively), preexisting nicotine CS (d = 0.57, 95% CI, -0.02 to 1.15), and nicotine priming (CS1, d = 0.82, 95% CI, 0.22-1.41 and CS2, d = 0.78, 95% CI, 0.18-1.37, respectively; preexisting nicotine CS, d = 0.92, 95% CI, 0.31-1.52), as well as nicotine craving induced by the preexisting nicotine CS (d = 0.64, 95% CI, 0.05-1.22), and nicotine priming (d = 1.15, 95% CI, 0.52-1.76)., Conclusions and Relevance: In rat-to-human translational study, a novel UCS-induced memory retrieval-reconsolidation interference procedure inhibited nicotine craving induced by exposure to diverse nicotine-associated CS and nicotine itself. This procedure should be studied further in clinical trials.

In the process of steel manufacture, up to ten millions of tons of sintering dust (SD) are produced annually in China, which contain noble metals such as Ag. Therefore, recovery of silver (Ag) from SD could be a potential economic and environmental activity. The purpose of this article is to generate information about reaction kinetics of silver leaching with thiourea from SD, comparing the conventional and ultrasonic-augment leaching. The effects of various control parameters such as the ultrasound power, particle size, leaching temperature and thiourea concentration on leaching rate of silver were studied. The results showed 89% silver recovery for conventional process against 95% for ultrasound assisted leaching. The ultrasonic wave increased the leaching rate and shorten the reaction time. The rate controlling step was analyzed using shrinking core model and the rate controlling step is identified to be the diffusion through the product layer in both conventional and ultrasonic-augment leaching processes. The activation energies were estimated to be 28.01kJ/mol and 18.19kJ/mol, and the reaction order were 0.89 and 0.71, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Recently, a number of double-image cryptosystems have been developed. However, there are notable security performance differences between the two encryption channels in these algorithms. This weakness downgrades the security level and practicability of these cryptosystems, as the cryptosystems cannot guarantee all the input images be transmitted in the channel with higher security level. In this paper, we propose a novel double-image encryption scheme based on cross-image pixel scrambling in gyrator domains. The two input images are firstly shuffled by the proposed cross-image pixel scrambling approach, which can well balance the pixel distribution across the input images. The two scrambled images will be encoded into the real and imaginary parts of a complex function, and then converted into gyrator domains. An iterative architecture is designed to enhance the security level of the cryptosystem, and the cross-image pixel scrambling operation is performed to the real and imaginary parts of the generated complex encrypted data in each round. Numerical simulation results prove that a satisfactory and balanced security performance can be achieved in both channels.

Objective: To investigate the therapeutic efficacy and safety of salbutamol and dexamethasone added into large-volume whole lung lavage (WLL) fluid in patients with pneumoconiosis., Methods: A total of 176 patients with pneumoconiosis were randomly divided into control group (n=86) and treatment group (n=90). The control group received WLL with 0.9% sodium chloride solution, while for the treatment group, salbutamol and dexamethasone were added into the WLL fluid for both lungs at the 1st and 4th WLLs.Before and after WLL, the pulmonary wheezing, arterial partial pressure of oxygen (Pa02), peak airway pressure(Pa peak), amount of intrapulmonary residual fluid, forced expiratory volume in one second (FEVw) (72 h later),diffusion capacity for carbon monoxide (DLCO ), and forced vital capacity (FVC) were measured for comparison between the two groups., Results: After WLL, the treatment group had a significantly lower detection rate of pulmonary wheezing than the control group ( 13.3% vs 29.1 %, x2=5.028, ?=0.025), and the control group had a significantly higher incidence rate of pulmonary wheezing than the treatment group (21.8% vs 3.7%, 0R=5.423,95%CI 2.036-9.568 ). Compared with the control group, the treatment group had significantly higher Pa02 and significantly lower Pa peak and amount of intrapulmonary residual fluid (t =2.163 -4.132, P<0.05) and significantly higher FEV1, DLCO, and FVC (t=1.986-2.345, P<0.05) after WLL., Conclusion: Salbutamol and dexamethasone added into large-volume WLL fluid may effectively alleviate bronchial spasm, reduce hypoxemia, and decrease Pa peak in patients with pneumoconiosis, thus promoting lung function recovery after WLL.

The 18 biochemical parameters of serum were measured to analyze the pathogenic risks of the Yangtze River Source of Drinking Water in Nanjing area (YZR-SDW-NJ) on mouse Mus musculus for protection of human health in this research. The male mice Mus musculus were sampled and fed with YZR-SDW-NJ for 90 days then the eighteen serum biochemical levels were measured with Automatic Biochemical Analysis/RerLi 600. And the parameter data were treated by One-Way ANOVA statistic approach. The results showed that five parameter levels for the sample group mice were different from those for the control group significantly (0.01 < P or 0.05 < P). Four 4 of the 5 altered parameter levels were decreased including glutamate pyruvate transaminase 38% lower, glutamine-oxaloacetic transaminase 24% lower, triglyceride 76% lower and cystatin C 73% lower, only creatinine level was 26% higher than that in the control group. The data suggest that YZR-SDW-NJ had toxicity on the mouse and the organic pollutants in YZR-SDW-NJ might lead to liver, kidney, cardiovascular and metabolic pathogenic risks on the human beings. The results might be cited as evidence to control pollutants in the source water for the protection of NJ people's health.