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The target article by Lynch et al. (2021) offers approaches for improving trial availability and Expanded Access for non-pandemic diseases based on the analysis of the COVID-19 experience in the US...

Background. The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. Methods. Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. Results. A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: OR = 1.25 , 95% CI 1.12-1.40, P < 0.01 ; homozygous model: OR = 1.33 , 95% CI 1.03-1.72, P = 0.029 , respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: OR = 1.17 , 95% CI 1.02-1.34, P = 0.023 ; recessive model: OR = 1.28 , 95% CI 1.13-1.45, P < 0.01 ; homozygous model: OR = 1.39 , 95% CI 1.05-1.86, P = 0.023 , respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: OR = 0.86 , 95% CI 0.74-1.00, P = 0.045 ). Conclusions. Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.

The occurrences of impaired lung function during childhood could substantially influence the health states of the respiratory system in adults. So, the effects of air pollution and green spaces on impaired lung function in children were investigated in this study. The lung function of each student was tested every year from 2015 to 2017 and the method of case-control study was applied. 2087 students aged from 9 to 11 years old of primary schools in Tianjin were ultimately included in this study. The method of propensity score matching (PSM) was performed to minimize the confounding bias and the conditional logistic regression model was carried out to evaluate the effects of indoor and outdoor environmental risk factors on the occurrences of impaired lung function in children. For every interquartile range (IQR) increase in the mixture of six air pollutants at the lag1, lag2, and lag3 periods, the risks of getting impaired lung function were increased by 53.4%, 34.7%, and 16.9%, respectively. The protective effect of greenness at lag2 period (odds ratios (OR)) = 0.022 (95% confidence interval (CI): 0.008-0.035)) was stronger than that at lag1and lag3 periods, respectively. Separate and combined effects of most air pollutants at different lag periods exerted hazardous effects on the lung function of students. Exposure to greenness had protective effects on the lung health of children.

Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment.In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury.We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against HMG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.

Dietary supplementation with sea cucumber saponins (SCS) and exercise have been confirmed to be effective in preventing the development of obesity and its related diseases. However, the combined effectiveness of these interventions has not been explored. Here, we studied whether the beneficial influences of exercise could be further enhanced by dietary supplementation with SCS in high-fat diet-fed KM (Kunming) mice. Mice were randomly divided into four groups, including the high-fat diet group (HF), the SCS group (HF-S), the exercise group (HF-E), and the combination of dietary SCS and exercise group (HF-S + E). There were eight mice in every group. The results demonstrated that the combination of dietary SCS and exercise could synergistically reduce fat accumulation. In particular, white adipose tissue decreased by 63% in the HF-S + E group compared with that in the HF group. SCS supplementation with exercise also improved peripheral markers, such as serum parameters and hepatic TG levels. Further mechanical testing indicated that the combined effects of dietary SCS and exercise on inhibiting fat accumulation might be attributed to the inhibition of lipid synthesis in the liver and the activation of lipolysis in white adipose tissue to increase energy consumption.

Hemorrhage is the phenomenon of blood loss caused by vascular trauma or other pathological reasons, which is life-threatening in severe cases. Because microhemorrhage is difficult to visually monitor and pre-treat in vivo, it is necessary to establish in vitro prediction methods to study the hemostasis mechanism in different physiological environments. In this study, a microfluidic bleeding model was developed to investigate the effect of blood flow shear on microvascular hemostasis. The results indicated that the regulation of blood shear rate on platelet aggregation affected the growth and morphology of hemostatic thrombus, and finally regulated the process of hemostasis. This in vitro model is significant to studies on hemostatic mechanisms, a reliable prediction of microhemorrhages, and an adjustment of the treatment scheme.

Cognitive deficiencies, which are caused by maternal omega-3 PUFA deficiency (O-3 Def), are likely to be more rapidly and easily reversed at younger ages with quicker DHA reversal. This study aims to compare the efficiency of short-term supplementation of DHA in the form of phospholipids (PL) and triglycerides (TG) and improve cognitive deficiency in the O-3 Def model during different periods of brain development (3-week and 7-week old). The animal's spatial task performance, brain PUFA concentration, histopathology, and expression of synapse-associated proteins in the hippocampus were then analyzed. We demonstrate here that DHA-PL shows improved efficiency in improving cognitive deficiency compared to DHA-TG, particularly for adult O-3 Def offspring. The superiority of DHA-PL also correlates with the specific elevation of synapse-associated proteins, including BDNF, DCX, GAP-43, Syn, and PSD95, except to higher brain DHA accretion. This work highlights the DHA-PL as a better DHA supplement for inferior brain development caused by maternal O-3 Def, especially regarding those who missed the optimal time window of neurodevelopment.

The target article by David Alfandre et al. (2021) offers a new ethical framework to guide COVID-19 contingency surge planning and response, and applies this ethical framework to three case example...

BackgroundMultiple policy initiatives encourage more cautious prescribing of opioids in light of their risks. Electronic health record (EHR) redesign can influence prescriber choices, but some redesigns add to workload.ObjectiveTo estimate the effect of an EHR prescribing redesign on both opioid prescribing choices and keystrokes.DesignQuality improvement quasi-experiment, analyzed as interrupted time series.ParticipantsAdult patients of an academic multispecialty practice and a federally qualified health center (FQHC) who received new prescriptions for short-acting opioids, and their providers.InterventionIn the redesign, new prescriptions of short-acting opioids defaulted to the CDC-recommended minimum for opioid-naïve patients, with no alerts or hard stops, such that 9 keystrokes were required for a guideline-concordant prescription and 24 for a non-concordant prescription.Main MeasuresProportion of guideline-concordant prescriptions, defined as new prescriptions with a 3-day supply or less, calculated per 2-week period. Number of mouse clicks and keystrokes needed to place prescriptions.Key ResultsAcross the 2 sites, 22,113 patients received a new short-acting opioid prescription from 821 providers. Before the intervention, both settings showed secular trends toward smaller-quantity prescriptions. At the academic practice, the intervention was associated with an immediate increase in guideline-concordant prescriptions from an average of 12% to 31% of all prescriptions. At the FQHC, about 44% of prescriptions were concordant at the time of the intervention, which was not associated with an additional significant increase. However, total keystrokes needed to place the concordant prescriptions decreased 62.7% from 3552 in the 6 months before the intervention to 1323 in the 6 months afterwards.ConclusionsAutocompleting prescription forms with guideline-recommended values was associated with a large increase in guideline concordance in an organization where baseline concordance was low, but not in an organization where it was already high. The redesign markedly reduced the number of keystrokes needed to place orders, with important implications for EHR-related stress.Trial Registrationwww.ClinicalTrials.gov protocol 1710018646

The target article by Laacke et al. (2021) focuses on the specific context of identifying people in social media with a high risk of depression by using artificial intelligence (AI) technologies. I...

Negative feelings caused by external stress can continually agonize adrenergic receptors via promoting catecholamine secretion, causing cardiovascular disease. This study examines the mechanism by which persistent β-adrenergic receptor agonism induces myocardial injury. A rat model of cardiac injury was herein established using isoproterenol (5 mg/kg, continuous intraperitoneal injection for 3 days), and multiomics technology combined with metabolomics and proteomics was used to explore the mechanism by which persistent β-adrenergic receptor agonism induces myocardial injury. The mechanism underlying this phenomenon was further verified at the cellular level. Isoproterenol-induced persistent β-adrenergic receptor agonism promoted the release of reactive oxygen species, and P53, S100-A9, and complement 3 were shown to be involved in complement system activation pathways. Our data have demonstrated that isoproterenol could trigger ROS/P53/S100-A9 positive feedback to aggravate myocardial damage associated with complement activation.

Power conversion efficiencies (PCEs) of solution-processed organic solar cells (OSCs) have recently reached 17.4% (certified) for single-junction devices. Crucial to this advancement is the development of non-fullerene acceptors (NFAs) since 2015. The recent A-DAD-A NFAs have attracted widespread attention because of their ladder-type electron-deficient-core-based central fused ring with improved transport properties and optimum energy levels. With the synergistic effect of electron-deficient-core and specific molecular geometry, the A-DADA molecules could achieve low voltage losses and high current generation at the same time, reaching new regimes of device physics and photophysics. This perspective will discuss the voltage losses in state-of-the-art A-DAD-A NFA-based OSCs and propose new molecular design strategies to achieve PCEs over 20% in OSCs based on these new acceptors by further decreasing their total voltage losses. Funding Agencies|National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [21875286]; National Key Research & Development Projects of China [2017YFA0206600]; Science Fund for Distinguished Young Scholars of Hunan ProvinceNational Natural Science Foundation of China (NSFC)National Science Fund for Distinguished Young Scholars [2017JJ1029]; Swedish Research Council VRSwedish Research Council [2018-06048]; Swedish Energy Agency EnergimyndighetenSwedish Energy Agency [2016-010174]; Stiftelsen For Strategisk Forskning through a Future Research Leader program [FFL18-0322]; NSERCNatural Sciences and Engineering Research Council of Canada

Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils' responses in allergic conjunctivitis are currently not completely understood. This study reports that conjunctival eosinophils comprise two populations-Siglec-Fint and Siglec-Fhi-in different life stages. Siglec-Fint eosinophils partly expressed CD34 and were in the immature (or steady) state. Siglec-Fhi eosinophils did not express CD34, sharply increased in number after short ragweed (SRW) pollen challenge, and were in the mature (or activated) state. Moreover, chemical sympathectomy by 6-hydroxydopamine reduced the recruitment and activation of eosinophils, whereas the activation of the sympathetic nerve system (SNS) with restraint stress accelerated the recruitment and activation of eosinophils in SRW-induced conjunctivitis. It was also found that two eosinophil populations expressed alpha-1a-adrenergic receptors (α1a-ARs); in SRW-induced conjunctivitis, treatment with an α1a-AR antagonist decreased eosinophil responses, whereas treatment with an α1a-AR agonist aggravated eosinophil responses. Thus, eosinophil responses in conjunctivitis are regulated by the SNS via α1a-AR signaling. SNS inputs or α1a-AR function may be potential targets for the treatment of allergic conjunctivitis.

Background Asian women usually view the oval face, with a beautiful curve and clear outline, as elegant. The fat and bloated mid-lower face, with an undefined outline, takes away from what they perceive to be a beautiful appearance. Not only a bone but also soft tissue determine the shape of the mid-lower face. In this article, we introduce a modified surgical method of soft tissue for mid-lower facial recontouring, which can improve the fat and undefined outline of the mid-lower face caused by benign masseter muscle hypertrophy and reduce subcutaneous fat accumulation at the same time. The operative technique is simple and effective with few complications. Methods The surgical treatment of 36 patients who met the adaptation criteria was carried out by laser-assisted liposuction combined with masseter muscle dissection. All patients were followed up postoperatively, and the surgical efficacy was evaluated on the basis of: the comparison of facial contours of patients before and after surgery, the change of masseter muscle thickness detected by B-ultrasound imaging, the satisfaction of patients with postoperative facial contour improvement, and the incidence of complications. Results Between March 1, 2018, and August 31, 2019, 36 patients with indications underwent this procedure. The follow-up lasted 6 to 12 months postoperatively and demonstrated that all patients were satisfied with the postoperative results, of which 33 cases (91.7%) were very satisfied, and 3 cases (8.3%) were satisfied with the treatment and had obvious improvement of the appearance of their mid-lower face. Preoperatively, the average mandibular bigonial breadth was 138.6±8.3 mm, and the average thickness of the masseter muscle was 13.9±0.8 mm; the postoperative breadth was 123.3±7.7 mm, and the thickness was 10.1±0.2 mm. The average reduction of the lower face width and masseter thickness were 15.2±2.1 mm and 3.8±0.1 mm, respectively. No complications occurred among the 36 patients. Conclusion The described method makes a great improvement in reshaping the outline of the mid-lower face, improves the fat and unclear outline of the mid-lower face caused by masseter muscle hypertrophy, and reduces subcutaneous fat accumulation. The procedure is easy to perform and is minimally traumatic, allowing for a quick recovery with few complications. These advantages along with the patients’ overall satisfaction with the results make it worthy of clinical application.

Background There is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables. Methods We conducted an umbrella review of all systematic reviews of observational studies (with/without meta-analysis) that evaluated risk factors of CRC metastasis and recurrence. We also generated an updated synthesis of risk prediction models for CRC metastasis and recurrence. We cross-assessed individual risk factors and risk prediction models. Results Thirty-four risk factors for CRC metastasis and 17 for recurrence were investigated. Twelve of 34 and 4/17 risk factors with p vascular invasion for lymph node metastasis [LNM] in pT1 CRC) presented convincing evidence. We identified 24 CRC risk prediction models. Across 12 metastasis models, six out of 27 unique predictors were assessed in the umbrella review and four of them changed the odds of the outcome at least 3-fold. Across 12 recurrence models, five out of 25 unique predictors were assessed in the umbrella review and only one changed the odds of the outcome at least 3-fold. Conclusions This study provides an in-depth evaluation and cross-assessment of 51 risk factors and 24 prediction models. Our findings suggest that a minority of influential risk factors are employed in prediction models, which indicates the need for a more rigorous and systematic model construction process following evidence-based methods.

Magnetic flux ropes observed as magnetic clouds near 1 au have been extensively studied in the literature and their distinct features are derived using numerous models. These studies summarize the general characteristics of flux ropes at 1 au without providing an understanding of the continuous evolution of the flux ropes from near the Sun to 1 au. In the present study, we investigate 26 flux ropes observed by the Helios 1 and 2 spacecraft (from 0.3 to 1 au) using the velocity-modified Gold–Hoyle model. The correlation and regression analyses suggest that the expansion speed, poloidal speed, total magnetic helicity and twist per au of the flux rope are independent of heliospheric distance. The study implies that the aforementioned features are more strongly influenced by their internal properties compared with external conditions in the ambient medium. Moreover, the poloidal magnetic flux and magnetic energy of the studied flux ropes exhibit power-law dependence on heliospheric distance. A better understanding of the underlying physics and corroboration of these results is expected from the Parker Solar Probe measurements in the near future.

The Solar Ring mission, a concept to monitor the Sun and inner heliosphere from multiple perspectives, has been funded for pre-phase study by the Strategic Priority Program of Chinese Academy of Sciences in space sciences. The Solar Ring is comprised of 6 spacecraft, grouped in three pairs, moving around the Sun in an elliptical orbit in the ecliptic plane. The mission costs, including launch fee, deep-space maneuvers, and deployment time of the ring, are highly relevant to the working orbit, deep-space transfer, and phase angle within a group. The preliminary mission profile is analyzed and designed in this paper. The launch way, two spacecraft with one rocket, is adopted. The deployment time, phasing maneuvers, and C3 of launch energy are evaluated for the elliptical orbits with the perihelion between 0.7 and 0.9 AU using the rockets of Long March (LM) 3A and 3B. Numerical simulations show two candidate trajectories: fast deployment within 4 years by LM-3B, medium deployment more than 6 years by cheaper rocket of LM-3A. In order to obtain both fast deployment and low launch cost, another orbit profile is proposed by shortening the phase angle within a group. The suggested working orbits and the corresponding costs of launch, deployment time, and phasing maneuvers will strongly support the science objectives.

As one of the seven scientific payloads on board the Tianwen-1 orbiter, the Mars Orbiter Magnetometer (MOMAG) will measure the magnetic fields of and surrounding Mars to study its space environment and the interaction with the solar wind. The instrument consists of two identical triaxial fluxgate magnetometer sensors, mounted on a 3.19 meter-long boom with a seperation of about 90 cm. The dual-magnetometers configuration will help eliminate the magnetic field interference generated by the spacecraft platform and payloads. The sensors are controlled by an electric box mounted inside the orbiter. Each magnetometer measures the ambient vector magnetic field over a wide dynamic range (to 10,000 nT per axis) with a resolution of 1.19 pT. Both magnetometers sample the ambient magnetic field at an intrinsic frequency of 128 Hz, but will operate in a model with alternating frequency between 1 and 32 Hz to meet telemetry allocations.

Purpose The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs) is increasing globally; however, little has been reported on the risk factors and outcomes of CRKP BSIs in central China. This study aimed to determine the clinical risk factors for CRKP BSIs and the outcomes of CRKP BSIs. Patients and Methods We performed a case-control study of 239 patients with K. pneumoniae BSIs who were treated at Henan Provincial People's Hospital between July 2017 and July 2018. The cases (n=98, 41%) had CRKP BSIs, and the controls (n=141, 59%) had non-carbapenem-resistant K. pneumoniae (non-CRKP) BSIs. Antimicrobial sensitivity was determined using automated broth microdilution and an agar disk diffusion method. Data were obtained from clinical and laboratory records. Multivariate logistic regression and Pearson chi-square tests were used to identify clinical factors and outcomes associated with carbapenem resistance. Results Risk factors for carbapenem resistance included recent carbapenem use (odds ratio [OR]: 9.98, 95% confidence interval [CI]: 5.2-17.1, P

We propose and realize a spatial phase modulation laser interferometer (SPMLI), which mainly consists of a laser source, an optical fiber, a transparent plate and a linear charge coupled device (CCD). The reflected beams from the upper and lower surfaces of the transparent plate produce two-beam interference. The generated spatial phase modulation interference image is taken by the CCD. The spatial frequency of the image is proportional to the wave number of the laser light and the thickness of the transparent plate. Experimental results show that the wavelength and thickness can be measured in picometer-level and nanometer-level resolution, respectively. Compared with other interferometers, the proposed interferometer has the advantages of simple structure, low cost and no need for mechanical scanning components.

With the slowdown of the progressive pace of miniaturization, the development of microelectronic systems shows diverse features. This leads to the emergence of new types of packages and challenges, demanding systematic approaches to sort out characteristic issues, increase insightful visions and map out progressive schemes. Focusing on mechanical characterization, this paper identifies mechanical challenges emerged in the current and future progresses of microelectronic packages. Mechanical challenges are firstly identified from the three categories of new issues, thermal interfaces and new structural patterns to highlight the key points. This is then followed by a discussion of mechanical characterization on the aspects of the domination of surface effects, the coupling of material-structural integration and the advent of multiphysical systems to describe the main schemes. Finally, mechanical issues expected in the ongoing future are analyzed through three aspects of stacked 3D structures, in-situ packages and nanomechanics to give a perspective view. Miniaturization is highlighted as the fundamental reason bringing significant changes and issues to mechanics. The interactive couplings on interfaces and between nanomaterial phases are emphasized as the phenomenal issues for mechanical investigations. By highlighting the characteristics and challenges with mechanics, this paper roughly profiles a framework of mechanical issues of microsystems.

The study aims to explore the distribution characteristics and influencing factors of diabetic retinopathy (DR) in diabetes mellitus (DM) patients and association rules of eye diseases in these patients. Data were obtained from 1284 DM patients at Henan Provincial People’s Hospital. Association rules were employed to calculate the probability of the common occurrence of eye-related diseases in DM patients. A web visualization network diagram was used to display the association rules of the eye-related diseases in DM patients. DR prevalence in people aged P P

Background: Worldwide, lung cancer has the highest mortality rate, and pulmonary tuberculosis has a high incidence in China, and both may be misdiagnosed frequently because of similar clinical presentation and atypical imaging findings. Diagnostic biomarkers to distinguish between lung cancer and other pulmonary diseases can be detected by metabolomics to avoid non-essential treatment.Methods: This cohort study employed non-targeted and targeted metabolomic analysis in participants enrolled from three independent centers. Multivariate statistics, variable importance in the projection parameter, receiver operating characteristics (ROC) curve were used to build potential key diagnostic biomarkers model of lung cancer and these were subsequently analyzed using targeted metabolomics in test set. Quantitative analysis of differences in biomarker levels was conducted, and a support vector machine (SVM) classifier was used to identify the prediction rate of diagnostic biomarker model. Results: Phenylalanylphenylalanine showed opposite trends in lung cancer and tuberculosis. The area under the curve 0.8887 (95% CI 0.8064–0.9710, pConclusions: Changes in the levels of phenylalanylphenylalanine facilitate differential diagnosis between lung cancer and tuberculosis, thereby potentially reducing the damage caused by misdiagnosis in the clinical setting, and enabling early treatment of lung cancer patients.Trial registration: This study is registered in the China Clinical Trial Registration Center (registration number ChiCTR2000040666, Registered 07 December 2020, http://www.chictr.org.cn/index.aspx)

High correlation, large radiation range, and deep impact are the characteristics of aerospace product common quality problems, which have been an important research field of aerospace quality management over the years. At present, the treatment of common quality problems focuses on the research of management mechanism and work mode, and relies on the experience level of the processing personnel. How to mine and identify common factors of the high-dimensional under-information description is the difficulty in the identification and management of common quality problems. Structured data is formed by proposing normative criteria for quality problem data, extracting characteristic indicators that describe the characteristics of common quality problems, using the optimal transfer matrix to define the index weights, calculating and determining the comprehensive similarity between the characteristic examples and the problem examples, and constructing and forming a common set of quality-problem relevant characteristic examples. Identify and analyze the data attributes that have a greater impact on the common factors, and construct the value distribution vector of the quality-problem common set. According to the characteristics of the value distribution of the common set attributes, the value concentration degree of each attribute for the common set is calculated, the common factors existing on the common set of quality problems are analyzed and identified, which can promote the effective management of the common quality problems.

Emerging evidence suggests that the reduction of ethanolamine plasmalogen (PlsEtn) is associated with in Alzheimer's disease and metabolic diseases. However, the mechanistic bases for PlsEtn on the these diseases are not well understood. Plasmalogens are primarily synthesized in the liver and enriched in brain. To this end, the present study sought to investigate the potential role of PlsEtn on steatohepatitis and memory impairments and its underlying mechanism. Here we show that peroxisome dysfunction and impairment of PlsEtn synthesis pathway occurs in both of hippocampus and liver, resulting in the decrease of PlsEtn level in APP/PS1 mice and HFD-fed mice. shGNPAT induced PlsEtn deficiency in hepatocytes induces p75NTR enhancement leading to decreased lipolysis activity, thereby exacerbating steatosis. Moreover, in the brain, PlsEtn administration appears to not only improve steatosis but also prevent Alzheimer's disease through restoration of TrkA/p75NTR balance. Together, our findings reveal a molecular mechanistic insight into the preventive role of plasmalogen modulation against steatosis and memory impairments via p75NTR inhibition., Graphical abstract The potential of plasmalogen modulation as a therapeutic strategy in lipid accumulation and memory impairments was demonstrated, and p75NTR was identified to play a pivotal role on the effect of PlsEtn in lipid accumulation and cognitive impairment.Image 1, Highlights • Peroxisome dysfunction and impairment of plasmalogen synthesis pathway resulted in the decrease of plasmalogen level. • Plasmalogen deficiency in hepatocytes induces p75NTR enhancement leading to decreased lipolysis activity. • Ethanolamine plasmalogen administration improves memory impairments by restoration of TrkA/p75NTR balance. • Ethanolamine plasmalogen administration attenuates neurodegeneration and neuronal death, and mitigates oxidative stress.

Most athletes continually endure mental and physical stress from intense exercise. Fructo-oligosaccharide (FOS) can reduce physical exhaustion, but the concrete mechanism behind it still needs further research. In this study, the effect of FOS on colonic mucosal barriers was investigated using an exercise-induced stress mouse model. Except for control individuals, mice were subject to cycles of 2-day exercise (at 20 rpm) interleaved by 5-day rest. The mice experienced a total of 6 days of exercise during the feeding period. FOS improved common indicators of exhaustion, such as glycogen storage in muscle. 16S rRNA data supported that changes in the gut microbiome were also closely related to stress status. Notably, Anaerotruncus was increased in mice under stress, while FOS facilitated the growth of Dorea, which is negatively associated with exhaustion. The RNA-seq analysis revealed that FOS could maintain the integrity of colonic epithelial barriers. For example, FOS significantly restored the expression of tight junctions (Occludin and Zonula occludens-1) in the colon, which was impaired under a stress state. Besides, the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome might contribute to the protection of the colonic mucosa by promoting the secretion of IL-18, Mucin2 (Muc2) and intestine lectin 1 (Itln1) in FOS-treated individuals. In short, FOS administration attenuated the damage of colonic mucosal barriers in exercise-induced stressed mice.

The reflectometry on Experimental Advanced Superconducting Tokamak (EAST) is undergoing an upgrade for more comprehensive measurement of plasma density profile and fluctuation. The Data Acquisition and Control System (DACS) has been redeveloped to satisfy the requirements of the upgraded reflectometry. The profile reflectometry works in 30-110 GHz (X-mode) and 40-90GHz (O-mode), when the fluctuation reflectometry operates at 20 fixed frequency points in 50-110GHz (X-mode) and 20-60GHz (O-mode). The PXIe-based DACS includes two 8-channel 14-bit 250MSPS digitizers and ten 8-channel 12-bit 60MSPS digitizers. A self-developed 5-channel 250MSPS arbiter waveform generator (AWG) is used to control voltage control oscillators for frequency sweeping. A trigger and clock manger and a timing module receive the trigger and clock signal from central controller and synchronize all the digitizers and the AWG. The total data rate from digitizers is 2515 MB/S. The Data from digitizers is streamed to a disk array (RAID 0) with data throughput capacity of 3000 MB/S. Meanwhile, selected data is transported to a FPGA based real-time data processing module, which utilize a pre-trained neural network to calculate the plasma density profile. Now the new reflectometry is being installed on EAST, and its performance will be tested in experimental campaign after 2018., 21st IEEE Real Time Conference

The Editors of the Journal of Geophysical Research Space Physics would like to honor and thank the 2018 manuscript reviewers for the journal. This is a large‐scale, community‐wide effort for which 1,358 scientists submitted 3,027 reviews in 2018. We understand that this is a volunteer task and we greatly appreciate your time and effort to fulfill this service role back to the research community.

Background Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. Methods Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA

Keloids are the most common pathological form of trauma healing, with features that seriously affect appearance and body function, are difficult to treat and have a high recurrence rate. Emerging evidence suggests that miRNAs are involved in a variety of pathological processes and play an important role in the process of fibrosis. In this study, we investigated the function and regulatory network of miR-152-5p in keloids. The miRNA miR-152-5p is frequently downregulated in keloid tissue and primary cells compared to normal skin tissue and fibroblasts. In addition, the downregulation of miR-152-5p is significantly associated with the proliferation, migration and apoptosis of keloid cells. Overexpression of miR-152-5p significantly inhibits the progression of fibrosis in keloids. Smad3 is a direct target of miR-152-5p, and knockdown of Smad3 also inhibits fibrosis progression, consistent with the overexpression of miR-152-5p. The interaction between miR-152-5p and Smad3 occurs through the Erk1/2 and Akt pathways and regulates collagen3 production. In summary, our study demonstrates that miR-152-5p/Smad3 regulatory pathways involved in fibrotic progression may be a potential therapeutic target of keloids. [BMB Reports 2019; 52(3): 202-207].

Background Considering that the quality control indicators in Chinese medicine (CM) are disconnected from safety and effectiveness, Prof. Chang-xiao Liu et al. has proposed a concept regarding the quality marker (Q-marker) of CM to promote the healthy development of the CM industry and improve the CM quality control method. Purpose In this study, we proposed a strategy to discover and verify the toxicity Q-marker of CM based on network toxicology. Methods First, traditional biochemical pathology indicators and sensitive biomarkers were used to predict the toxicity of CM. Next, the chemical composition of toxic CMs and their metabolites were rapidly identified by multidimensional detection techniques. Subsequently, the interaction network between “toxicity - toxic chemical composition - toxic target - effect pathway” was built through network toxicology, and the potential toxicity Q-marker of CM was initially screened. Finally, the chemical properties of toxicity Q-markers were verified by traceability and testability. Results Based on the predicted results of network toxicology, the toxic compounds of CM were preliminarily identified, and the toxic mechanism was comprehensively interpreted. In the context of definite biological properties and chemical properties, the toxicity Q-marker was finally confirmed. Conclusion This extensive review provides a study method for the toxicity Q-marker of CM, which helps to systemically and thoroughly reveal the internal toxicity mechanism of CM. The in-depth study of the toxicity Q-marker provides the material basis and technical support for the safety evaluation of CM.

Here, we report the first imported case of melioidosis from Laos in central China. COMPACT VITEK2 identification system and PCR, as well as sequencing methods confirmed that the patient was infected by Burkholderia pseudomallei, a bacterial species closely related to an isolate detected in Thailand. These findings are highly valuable for an early diagnosis, treatment and to prevent the spread of this emerging infectious disease in central China.

Cisplatin is an effective chemotherapeutic agent used in the treatment of various cancers. However, its use is usually complicated by nephrotoxic side effects, which limit its clinical application. Interestingly, DHA supplementation has been found to exhibit anticancer activity without any side effects. It is noted that DHA-PC has been applied in the treatment of kidney diseases. Our aim in the current study was to investigate whether DHA-PC treatment could alleviate cisplatin-induced nephrotoxicity using a Balb/c mice model. Our results showed that DHA-PC could significantly prolong the survival time, while the traditional DHA had no remarkable changes. In addition, short supplements of DHA-PC alleviated the cisplatin-induced kidney dysfunction, such as increased levels of blood urea nitrogen and creatinine. DHA-PC could protect the kidneys against cisplatin-induced toxicity, which might be attributed to the sirtuin 1 activation and the inhibition of oxidative stress and apoptosis. These findings suggest that DHA-PC might be a new dietary strategy for the treatment of nephrotoxicity.

Hyperlipidemia with the characteristic of excessive blood lipid level is a risk factor for stroke, coronary heart disease, myocardial infarction, hypertension, impaired glucose tolerance, diabetes, sudden death, and so on. Therefore, we should pay more attention to the dangers of hyperlipidemia and look for natural lipid-lowering ingredients to prevent and relieve hyperlipidemia. In recent years, various studies have shown that active ingredients from marine foods exhibit obvious anti-hyperlipidemia activity, which have attracted more and more researches' attention. This paper shows that the regulatory mechanisms of lipid metabolism mainly include the cholesterol metabolism balance and the metabolism balance of triglyceride and fatty acid. This paper also summarizes active ingredients from marine foods with the role of treating or preventing hyperlipidemia, and relevant literature published in the past decades are reviewed. The active ingredients from marine foods are divided into polysaccharides, lipids, proteins, saponins, polyphenols and others, which are described in this article from the aspects of active ingredients, sources, models, efficacy and mechanisms. This paper may provide a valuable reference for the development of functional ingredients from marine foods with anti-hyperlipidemia activity.

A low-energy ion spectrometer (LEIS) for use aboard three-axis stabilized spacecraft has been developed to measure ion energy per charge distribution in three-dimensional space with good energy-, angular- and temporal-resolutions. For the standard top-hat electrostatic analyzer used widely in space plasma detection, three-axis stabilized spacecraft makes it difficult to obtain complete coverage of all possible ion arrival directions. We have designed angular scanning deflectors supplementing to a cylindrically symmetric top-hat electrostatic analyzer to provide a half-space field of view as 360°×90° (–45°–+45°), and fabricated the LEIS flight model for detecting magnetospheric ions in geosynchronous orbit. The performance of this payload has been evaluated in detail by a series of simulation and environmental tests, and the payload has also been calibrated through laboratory experiments using a low-energy ion source. The results show that capabilities of the LEIS payload are in accordance with the requirements of a magnetospheric mission.

Antimicrobial peptide (AMP) can be a promising alternative in various domains. However, further risk information is required. In this study, mice were orally administrated different dosages of recombinant AMP microcin J25 (4.55, 9.1, and 18.2 mg/kg; MccJ25) for 1 week, and the toxicity risk impacts were examined. We evidenced that middle-dosage administration mice had a lower inflammation, better body weight, and ameliorated mucosal morphology, accompanied by reduced intestinal permeability and tighter intestinal barrier. Fecal microbiota composition analysis in middle- or low-dosage mice revealed the Bifidobacterium count was increased and the coliform bacteria count was decreased, and increased in short-chain fatty acid levels. Unexpectedly, there was a risk that high-dosage mice increased intestinal permeability and imbalance of intestinal bacteria. Taken together, these data indicated a safe threshold for usage of MccJ25 in clinical practice. Such studies can effectively enhance the safety of various aspects such as food preservative and drug.

JUNO is a 20-kton liquid scintillator detector aiming to determine the neutrino mass ordering, precisely measure the oscillation parameters, detect the astrophysical neutrinos and search for exotic physics. It is designed to reach an energy resolution of 3% at 1 MeV with the highest ever PMT coverage, using two types of 20 inch phototubes: MCP-PMT from NNVT and dynode-PMT from Hamamatsu. In this article, the gain and charge response of the MCP and dynode PMTs are investigated with the study of JUNO Central Detector prototype. The linearity of the MCP-PMT charge output is measured too to check the effect of a long tail on its charge spectrum.

Chronic spontaneous urticaria (CSU) is a common skin disease which symptom is local pruritus and pain. In medicine, researchers take a certain point that the brain is the control center of CSU, but in previous experiments, the researchers found that cerebellum also had a certain effect on CSU. In order to find out the influence of CSU in the brain and cerebellum, we collected the brain resting-state fMRI data from 40 healthy controls and 32 CSU patients and used DPABI to preprocess. We calculated the entropy values of five scales by using multiscale entropy (MSE) and the average entropy values of two groups’ BOLD signals; 15 regions with significant differences were found which not only had a more detailed impact in the brain but also had an impact in the cerebellum, such as precentral gyrus, lenticular putamen, and vermis of cerebellum. In addition, we found that compared with the healthy controls, the entropy values of CSU patients showed two trends which need further study. The advantage of our experiment is that the multiscale entropy value is used to get more influence regions of CSU in the brain and cerebellum. The results of this paper may provide some help for the pathological study of CSU.

Background DHA (22:6n-3), a long-chain n-3 PUFA, is essential for normal brain development and function. Our previous study demonstrated that DHA significantly improves scopolamine-induced dementia. However, there are no reports on the relation between n-3 PUFA deficiency and scopolamine-induced cognitive impairment. Objectives The aim of this study was to evaluate whether n-3 PUFA deficiency increases vulnerability to scopolamine-induced cognitive impairment. Methods Male and female C57BL/6 mice were mated and fed an n-3 PUFA-adequate [containing 2.88% α-linolenic acid (ALA; 18:3n-3)] or -deficient (containing 0.09% ALA) diet for 2 consecutive generations. The corresponding second-generation male offspring were kept on the same diet as their mothers after weaning, and were randomly assigned to 2 subgroups at 7 wk of age, in which they were intraperitoneally injected with saline [fed n-3 PUFA-adequate (Con) or -deficient (Def) diet] or scopolamine [5 mg/kg body weight; fed n-3 PUFA-adequate (Sco) or -deficient (Def + Sco) diet] once per day for 7 d before killing. Behavioral performance was analyzed using the Morris Water Maze test. Fatty acid composition, protein expression, and indicators of cholinergic and oxidative stress in the brain were measured. Results The Def group showed lower brain DHA (-63.7%, P ≤ 0.01) and higher n-6 PUFA (+65.5%, P ≤ 0.05) concentrations than the Con group. The Def + Sco group and the Sco group showed poorer spatial learning and memory (escape latency on the sixth day: +60.3% and +36.8%; platform crossings: -43.9% and -28.2%, respectively) and more obvious cholinergic dysfunction (acetylcholine: -47.6% and -27.7%, respectively), oxidative stress (glutathione peroxidase: -64.2% and -32.5%, respectively), apoptosis [B-cell lymphoma 2 (BCL2)-associated X protein/BCL2: +230.8% and +153.8%; phosphorylated P38/P38: +232% and +130%, phosphorylated c-Jun N-terminal kinase (JNK)/JNK: +104.5% and +58.8%, respectively], neuroinflammation (IL-1β: +317.6% and +95%, respectively), and neurodevelopmental delay (brain-derived neurotrophic factor: -54.4% and -7.25%, respectively) than their corresponding saline-treated controls. Conclusions Dietary n-3 PUFA deficiency significantly decreases brain DHA concentrations and increases vulnerability to scopolamine-induced cognitive impairment in C57BL/6 male mice.

Background: There is no study that has systematically investigated the breadth and validity of the associations of folate and multiple health outcomes. We aimed to evaluate the quantity, validity, and credibility of evidence regarding associations between folate and multiple health outcomes by using umbrella review of meta-analysis.Methods: We searched the MEDLINE, EMBASE, and Cochrane Library databases from inception to May 20, 2018, to identify potential meta-analyses that examined the association of folate with any health outcome. For each included meta-analysis, we estimated the summary effect size and their 95% confidence interval using the DerSimonian and Laird random-effects model. We used the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) to assess methodological quality and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation working group classification) to assess the quality of evidence for each outcome included in the umbrella review.Results: Overall, 108 articles reporting 133 meta-analyses of observational studies and 154 meta-analyses of randomized controlled trials (RCTs) were included in the study. Among them, 108 unique exposure–outcome–population triplets (referred to as unique meta-analyses hereafter) of RCTs and 87 unique meta-analyses of observational studies were reanalyzed. Beneficial effects of folate were observed in the all-cause mortality rate and in a number of chronic diseases, including several birth/pregnancy outcomes, several cancers, cardiovascular disease and metabolic-related outcomes, neurological conditions, and several other diseases. However, adverse effects of folate were observed for prostate cancer, colorectal adenomatous lesions, asthma or wheezing, and wheezing as an isolated symptom and depression.Conclusions: Current evidence allows for the conclusion that folate is associated with decreased risk of all-cause mortality and a wide range of chronic diseases. However, folate may be associated with an increased risk of prostate cancer. Further research is warranted to improve the certainty of the estimates.

With the development of the fourier ptychography in microscopy imaging, more and more researchers consider applying fourier ptychography in long-distance imaging. However being different from microscopic imaging, long distance fourier ptychographic imaging will face more challenges, one of which is the source image quality. In this manuscript, the influence of the source image quality on camera scanning FP imaging will be investigated and simulated. In the first part, the calibration aims to solve the influence of unenenly illumination. After that, a poisson-gaussian mixed noise model based denoising is uesd and could effectively suppresses the noise through parameter estimation. Finally, Phase correalation regisitrtion has to be used to correct the mismatch between adjacent images caused by camera scanning mode. The simulation results demonstrate the effectiveness of the preprocessing methods and could make FP more robust.The signal to noise ratio could reach to 40.5dB while obtained 5×improvement in resolution.

Background and purpose Chronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management. Methods Forty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry. Results Compared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs. Conclusions Our findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.

Background Patients with Extracorporeal Membrane Oxygenation (ECMO) undergoing primary bronchial malignancy resection and left pneumonectomy via bilateral thoracic approach are rare for there exist few reports available to date. And the nursing experience about this disease is rare reported. Case presentation This study reported a 50-year-old man with adenoid cystic carcinoma in left main bronchus by computed tomography (CT), fiberoptic bronchoscopy, and puncture biopsy. The case is the first report about operation method and the comprehensive nursing care, including conventional nursing, airway management, fluid management, nutritional support, and psychosocial support for patients undergoing primary bronchial malignancy resection and left pneumonectomy. After multidisciplinary treatment and comprehensive care, the patient was cured and discharged on the 17th day after surgery. Conclusion This study reported a rare case with bronchial malignancy resection and left pneumonectomy and discussed its nursing care. A skilled management of ECMO, intraoperative position transformation, and prevention, as well as control of pulmonary complications are fundamental in caring patients with bronchial tumors. Monitoring of pulmonary function and blood pressure, adequate nutrition, and psychological support could be contributing factors for successful treatment during the postoperative stage.

Background Public health interventions have been implemented to contain the outbreak of coronavirus disease 2019 (COVID-19) in New York City. However, the assessment of those interventions—for example, social distancing and cloth face coverings—based on real-world data from published studies is lacking. Methods The Susceptible-Exposed-Infectious-Removed (SEIR) compartmental model was used to evaluate the effect of social distancing and cloth face coverings on the daily culminative laboratory confirmed cases in New York City (NYC) and COVID-19 transmissibility. The latter was measured by Rt reproduction numbers in 3 phases that were based on 2 interventions implemented during this timeline. Results Transmissibility decreased from phase 1 to phase 3. The initial R0 was 4.60 in phase 1 without any intervention. After social distancing, the Rt value was reduced by 68%, while after the mask recommendation, it was further reduced by ~60%. Conclusions Interventions resulted in significant reduction of confirmed case numbers relative to predicted values based on the SEIR model without intervention. Our findings highlight the effectiveness of social distancing and cloth face coverings in slowing down the spread of severe acute respiratory syndrome coronavirus 2 in NYC.

BACKGROUND Data on tenofovir alafenamide fumarate (TAF) for preventing mother-to-child transmission of hepatitis B virus (HBV) are lacking. AIMS To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother-to-child transmission. METHODS Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother-to-child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother-to-child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. RESULTS Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA

ObjectiveThe physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy.DesignInfants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants’ physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age.ResultsOf 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social–emotional, and adaptive behaviour measurements) were all comparable between the groups.ConclusionInfants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission.Trial registration numberNCT01488526.

Rationale: Epidemiological studies have identified an associate between iron deficiency (ID) and the use of oral contraceptives (CC) and ischemic stroke (IS). To date, however, the underlying mechanism remains poorly understood. Both ID and CC have been demonstrated to upregulate the level and iron-binding ability of Tf (transferrin), with our recent study showing that this upregulation can induce hypercoagulability by potentiating FXIIa/thrombin and blocking antithrombin-coagulation proteases interactions. Objective: To investigate whether Tf mediates IS associated with ID or CC and the underlying mechanisms. Methods and Results: Tf levels were assayed in the plasma of IS patients with a history of ID anemia, ID anemia patients, venous thromboembolism patients using CC, and ID mice, and in the cerebrospinal fluid of some IS patients. Effects of ID and estrogen administration on Tf expression and coagulability and the underlying mechanisms were studied in vivo and in vitro. High levels of Tf and Tf-thrombin/FXIIa complexes were found in patients and ID mice. Both ID and estrogen upregulated Tf through hypoxia and estrogen response elements located in the Tf gene enhancer and promoter regions, respectively. In addition, ID, administration of exogenous Tf or estrogen, and Tf overexpression promoted platelet-based thrombin generation and hypercoagulability and thus aggravated IS. In contrast, anti-Tf antibodies, Tf knockdown, and peptide inhibitors of Tf-thrombin/FXIIa interaction exerted anti-IS effects in vivo. Conclusions: Our findings revealed that certain factors (ie, ID and CC) upregulating Tf are risk factors of thromboembolic diseases decipher a previously unrecognized mechanistic association among ID, CC, and IS and provide a novel strategy for the development of anti-IS medicine by interfering with Tf-thrombin/FXIIa interactions.

BACKGROUND Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be an ideal endpoint for antiviral therapy and a final therapeutic target for chronic hepatitis (CHB). This study aimed to evaluate the HBsAg kinetics in CHB patients during peginterferon-alpha (Peg-IFN-alpha) treatment. MATERIAL AND METHODS A retrospective cohort study was performed using a case database, which included 151 patients who received Peg-IFN-alpha treatment and with HBsAg load of no less than 4 time points from May 1, 2018 to January 31, 2019. The HBsAg kinetic pattern was analyzed by Q-type clustering, and a clinical prognostic empirical model was constructed based on the HBsAg kinetic pattern of uncured patients. RESULTS Changes of HBsAg in 13 functionally cured patients were attributed to 3 kinetic patterns by cluster analysis, and there was a significant positive correlation between functionally cure time and baseline HBsAg. For uncured 116 patients with treatment duration longer than or equal to 56 days, 5 HBsAg kinetic patterns were obtained by cluster analysis, and the clinical prognosis empirical model was established. Finally, 13 new functionally cured patients preliminarily confirmed the rationality of the proposed empirical model. CONCLUSIONS According to empirical model, we recommend that the therapeutic regime should be timely adjusted to improve sustained response rate and reduce patients' medical burden for patients with second (Z type) and fifth (Z+W type) kinds of patterns. While for the rest of patterns' patients, it is recommended to continue treatment for a longer period of time to achieve the desired therapeutic goal.