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We designed a study to compare the newly developed 5-mg flunarizine hydrochloride capsules (test) to that of its marketed counterpart (5-mg; reference) among healthy adult Chinese volunteers. We performed an open-label, single-center study that consisted of 2 randomized, crossover trials, including a fasting trial and a fed trial. In each part of the study, the subjects were randomly assigned to either receive the test or reference products (5-mg flunarizine) in a 1:1 ratio. Subjects then received the alternative products, following a 14-day washout period. Concentrations of plasma flunarizine were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were evaluated using the WinNonlin software. The analysis of variance and Food and Drug Administration bioequivalence statistical criterion of 90% confidence interval for 80% to 125% range (set at P ≤ .05) of geometric means ratios of test: reference product for peak plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, and AUC from time 0 to infinity were determined. Tolerability was evaluated during the entire study period. Overall, 23 volunteers completed the fasting study, while 40 volunteers completed the fed study. The test formulation was found to be bioequivalent to the marketed formulation, as the 90% confidence interval for the ratio of geometric means of peak plasma concentration (fasting: 87.61%-101.67%; fed: 87.38%-104.06%), AUC from time 0 to time t (fasting: 89.44%-99.92%; fed: 92.65%-98.28%), and AUC from time 0 to infinity (fasting: 95.02%-104.33%; fed: 90.41%-96.96%) were within equivalence limits (80-125%) under both the fasting and fed conditions. When flunarizine was given alongside high-fat meals, time to maximum concentration was delayed ≈3.5 hours compared to fasting conditions. Meantime, high-fat meals increased its exposure by nearly 50%. Furthermore, there were no serious adverse events found among the subjects. This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and postprandial conditions.

BACKGROUND The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p

Summary Objectives Tuberculosis (TB) remains one of the public health problems worldwide. Rapid, sensitive and cost-effective diagnosis of Mycobacterium tuberculosis (M.tb) is critical for TB control. Methods We developed a novel M.tb DNA detection platform (nominated as TB-QUICK) which combined loop-mediated isothermal amplification (LAMP) and CRISPR-Cas12b detection. TB-QUICK was performed on pulmonary or plasma samples collected from 138 pulmonary TB (PTB) patients, 21 non-TB patients and 61 close contacts to TB patients. Acid-fast bacillus (AFB) smear, M.tb culture and GeneXpert MTB/RIF (Xpert) assays were routinely conducted in parallel. Results By targeting M.tb IS6110, TB-QUICK platform could detect as low as 1.3 copy/μL M.tb DNA within 2 h. In pulmonary TB samples, TB-QUICK exhibited improved overall sensitivity of 86.8% over M.tb culture (66.7%) and Xpert (70.4%), with the specificity of 95.2%. More significantly, TB-QUICK exhibited a superior sensitivity in AFB-negative samples (80.5%) compared to Xpert (57.1%) and M.tb culture (46.2%). In the detection of plasma M.tb DNA by TB-QUICK, 41.2% sensitivity for AFB-positive and 31.7% for AFB-negative patients were achieved. Conclusion In conclusion, TB-QUICK exhibits rapidity and sensitivity for M.tb DNA detection with the superiority in smear-negative paucibacillary TB patients. The clinical application of TB-QUICK in TB diagnosis needs to be further validated in larger cohort.

M protein is often expressed in multiple myeloma and also can be detected in several lymphoma such as Waldenstrm macroglobulinaemia. M protein level can reflect the malignant degree and even genetic abnormality of multiple myeloma and lymphoma to some extent to predict the progress of the diseases, and the therapeutic response and prognosis of the disease can be evaluated by monitoring the M protein level and its change degree. This article reviews the role of M protein in the progression and prognosis of multiple myeloma and lymphoma, and discusses the differences in M protein expression between multiple myeloma and lymphoma, in order to provide new insights for clinical diagnosis, monitoring and evaluation of therapeutic effect.M蛋白在多发性骨髓瘤与淋巴瘤中的临床作用.M蛋白常表达于多发性骨髓瘤中，也可在华氏巨球蛋白血症等多种淋巴瘤中检测到。M蛋白水平可在一定程度上反映多发性骨髓瘤和淋巴瘤的恶性程度甚至是遗传异常从而预测疾病进展，并可通过监测M蛋白水平及其变化程度评估疾病治疗反应和预后。本文主要介绍M蛋白在多发性骨髓瘤和淋巴瘤中的进展判断及预后评估中的作用，并讨论M蛋白在多发性骨髓瘤和淋巴瘤中的表达差异，以期为临床提供疾病诊断、监测及疗效评估的新思路。.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma harboring an ASPL-TFE3 fusion gene. Herein, we report a case of ASPS associated with brain metastasis. Immunohistochemistry (IHC) for TFE3 antigen expression and fluorescence in situ hybridization (FISH) for TFE3 rearrangement were performed to arrive at an accurate diagnosis.A 47-year-old man was hospitalized for a headache and numbness of the lower limbs.Preoperative computed tomography and magnetic resonance imaging revealed 2 brain masses, 1 each in the right parietal and temporal bones. We diagnosed this case as ASPS with brain metastasis based on histological morphology, IHC, and FISH.The patient underwent right skull titanium mesh implantation and supratentorial superficial lesion resection.: The patient recovered well after discharged from hospital.The diagnosis of ASPS depends on careful clinical, radiographic, histopathological, IHC, and FISH assessments to arrive at the correct diagnosis. Thus, TFE3 may be useful in the diagnosis and treatment of ASPS.

Grassland degradation has become a worldwide ecological problem. Although soil microorganisms, as the main participants in the process of grassland degradation, play a key role in maintaining ecosystem function and improving soil productivity, little is known about the changes in microbial communities caused by grassland degradation and their relationship with soil properties and plant communities. In this study, we used Illumina MiSeq sequencing to analyze the soil fungal communities of subalpine meadow soil at four different degradation stages[i.e., non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD)] on Mount Wutai. The results showed that Ascomycota, Basidiomycota, and Zygomycota were the dominant phyla of soil fungi in the subalpine meadow, regardless of degradation stage. LEfSe showed that the subalpine meadows with different degradation degrees were enriched with different biomarkers. Compared with ND, MD and HD were enriched with more pathogenic fungi. Moreover, HD apparently decreased the richness and Shannon indexes of soil fungal communities compared with those of ND. Non-metric multidimensional scaling (NMDS) and similarity analysis (ANOSIM) indicated that the compositions and structures of fungal communities were significantly different among meadows with different degradation degrees (

Background Rice eating quality largely dictates consumer preference, and the demand for new rice varieties with excellent eating quality from farmers is increasing. Identification of factors contributing to eating quality is helpful for developing high-quality rice varieties. Results Two groups of rice with different apparent amylose content (AACs) were used in this study. One group contained four varieties with low AACs (8.8-9.4%), whereas the other contained four traditional varieties with medium AACs (17.2-17.5%). The physicochemical properties, starch fine structure and crystallinity and storage protein composition of the two groups were analyzed. We found that, in both groups, the rice varieties with high eating quality had more short-chain amylopectin, lower glutelin and prolamin content, and a higher albumin content. In addition, the low-AAC varieties produced opaque endosperms, which may result from an increased number of pores in the center of starch granules. Conclusions Both the fine structure of starch and the storage protein composition were closely related to rice eating quality. In both groups, short branch-chain amylopectin, short-chain amylopectin [degree of polymerization (DP) 6-12], and albumin had positive effects on eating quality. By contrast, long branch-chain amylopectin, long-chain amylopectin (DP 35-60), glutelin and prolamin had adverse effects on eating quality of rice. © 2020 Society of Chemical Industry.

OBJECTIVES An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P CONCLUSIONS The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.

Background: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. Methods: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-β1, TGF-β2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and β-catenin in FLSs. Results: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, β-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. Conclusions: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA. Key words: Dickkopf-1; Fibroblast-like synoviocytes; Rheumatoid arthritis; small interfering RNAs

Sleep quality is known to have a considerable impact on human health. Recent research shows that head and body pose play a vital role in affecting sleep quality. This paper presents a deep multi-task learning network to perform head and upper-body detection and pose classification during sleep. The proposed system has two major advantages: first, it detects and predicts upper-body pose and head pose simultaneously during sleep, and second, it is a contact-free home security camera-based monitoring system that can work on remote subjects, as it uses images captured by a home security camera. In addition, a synopsis of sleep postures is provided for analysis and diagnosis of sleep patterns. Experimental results show that our multi-task model achieves an average of 92.5% accuracy on challenging datasets, yields the best performance compared to the other methods, and obtains 91.7% accuracy on the real-life overnight sleep data. The proposed system can be applied reliably to extensive public sleep data with various covering conditions and is robust to real-life overnight sleep data.

Background Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. Methods The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. Results Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P Conclusions DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

To observe the moxibustion sensation and the clinical therapeutic effect of heat-sensitive moxibustion of two different suspension moxibustion methods and imitation moxibustion apparatus on mild to moderate knee osteoarthritis (KOA), and compare the therapeutic effect of different moxibustion methods.A total of 90 patients with mild to moderate KOA were randomized into a hand-held group (30 cases, 1 case dropped off), an imitation moxibustion apparatus group (30 cases) and a moxibustion shelf group (30 cases, 1 case dropped off).The compositions of moxibustion sensation and numbers of moxibustion sensation types in individuals in the hand-held group and the moxibustion shelf group were richer, the moxibustion sensation intensity was higher than that in the imitation moxibustion apparatus group (Heat-sensitive moxibustion can effectively treat knee osteoarthritis, while the different suspension moxibustion methods have an influence on clinical therapeutic effect, hand-held suspension moxibustion has the best efficacy.

This study was the first to compare the differences in trunk/shoulder kinematics and impact vibration of the upper extremity during backhand strokes in wheelchair tennis players and the able-bodied players relative to standing and sitting positions, adopting an electromagnetic system along with wearable tri-axial accelerometers upon target body segments. A total of 15 wheelchair tennis players and 15 able-bodied tennis players enrolled. Compared to players in standing positions, wheelchair players demonstrated significant larger forward trunk rotation in the pre-preparation, acceleration, and deceleration phase. Significant higher trunk angular velocity/acceleration and shoulder flexion/internal rotation angular velocity/acceleration were also found. When able-bodied players changed from standing to sitting positions, significant changes were observed in the degree of forward rotation of the trunk and shoulder external rotation. These indicated that when the functions of the lower limbs and trunk are lacking or cannot be used effectively, “biomechanical solutions” such as considerable reinforcing movements need to be made before the hitting movement. The differences between wheelchair tennis players and able-bodied players in sitting positions could represent the progress made as the wheelchair players evolve from novices to experts. Knowledge about how sport biomechanics change regarding specific disabilities can facilitate safe and inclusive participation in disability sports such as wheelchair tennis.

Background:. Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. Methods:. Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. Results:. Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246–15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. Conclusions:. The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Recent reports have established atherosclerosis (AS) as a major factor in the pathogenetic process of cardiovascular diseases such as ischemic stroke and coronary heart disease. Although the possible pathogenesis of AS remains to be elucidated, a large number of investigations strongly suggest that the inhibition of toll-like receptors (TLRs) alleviates the severity of AS to some extent by suppressing vascular inflammation and the formation of atherosclerotic plaques. As pattern recognition receptors, TLRs occupy a vital position in innate immunity, mediating various signaling pathways in infective and sterile inflammation. This review summarizes the available data on the research progress of AS and the latest antiatherosclerotic drugs associated with TLR pathway.

This clinical trial was conducted to assess the lipid-lowering activity of oat noodles by replacing partial staple food (wheat or rice noodle) in normal and mildly hypercholesterolemic subjects. Totally 84 healthy and mild hypercholesterolemic subjects were recruited and divided into 2 groups as experimental (oat noodles) and placebo (wheat noodles) and instructed to consume 100 g of oat noodles or wheat noodles (replacing one or two meals/day) for 10 weeks and followed by 2 weeks of follow up (without noodle consumption). Various anthropometric measurements and biochemical analysis were carried out during initial (baseline), 2nd, 6th, 10th and 12th week (follow-up). Consumption of oat noodles by replacing staple food for 10 weeks significantly reduced (**p

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30–78 years). After a median of 9 cycles BDex (range 1–9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome.

Purpose: This cross-sectional study assessed the associations of gender, age, level of intellectual disabilities (IDs) and of daily sedentary and physical activity (PA) time with physical fitness in adults with ID. Materials and methods: Sixty adults (mean age = 39.19 ± 11.70 years) with ID participated in this cross-sectional study. PA was monitored for 7 days using an ActiGraph GT3X monitor. Physical fitness was measured with a 6-min walking test, isometric push-up test, modified curl-up test, handgrip strength test, and back-saver sit-and-reach test. Results: (a) An age of ≥39 years and female gender were associated with lower performance in multiple aspects of physical fitness. (b) More moderate-to-vigorous PA (MVPA) was associated with greater muscular strength and endurance (modified curl-ups: β = 0.36, p &lt, 0.01, handgrip strength: right, β = 0.52, p &lt, left, β = 0.52, p &lt, 0.01). (c) More light-intensity PA (LPA) was associated with greater upper-body muscular endurance (β = 0.42, p &lt, 0.01) and greater flexibility (right leg: β = 0.36, p &lt, left leg: β = 0.38, p &lt, 0.01). Conclusion: LPA may be as beneficial as MVPA to the physical fitness of adults with ID. Future studies should focus on developing effective PA interventions for adults with ID, especially for women and individuals aged ≥39 years, by incorporating both LPA and MVPA.

Reproductive health is a key aim of the population health strategy, and male reproductive health constitutes an important part of reproductive health. This article systematically analyzes the applications to and grants from the National Natural Science Foundation of China (NSFC) and some related scientific problems in the field of male reproductive health in the past 30 years. It also discusses the development of the basic researches on male reproductive health in China and the facilitating role of NSFC in this field.

The herbal pair of Coptidis Rhizoma (CR) and Euodiae Fructus (EF) is a classical traditional Chinese medicine formula used for treating gastro-intestinal disorders. In this study, we established a systematic method for chemical profiling and quantification analysis of the major constituents in the CR-EF herbal pair. A method of ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) for qualitative analysis was developed. Sixty-five compounds, including alkaloids, phenolics, and limonoids, were identified or tentatively assigned by comparison with reference standards or literature data. The UHPLC fingerprints of 19 batches of the CR-EF herbal pair samples were obtained and the reference fingerprint chromatograms were established. Furthermore, nine compounds among 24 common peaks of fingerprints were considered as marker components, which either had high contents or significant bioactivities, were applied to quality control of the CR-EF herbal pair by quantitative analysis. This UHPLC-DAD analysis method was validated by precision, linearity, repeatability, stability, recovery, and so on. The method was simple and sensitive, and thus reliable for quantitative and chemical fingerprint analysis for the quality evaluation and control of the CR-EF herbal pair and related traditional Chinese medicines.

Aims: The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD). Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words “methotrexate,” “cardiovascular,” “acute coronary syndrome,” “coronary heart disease,” “myocardial infarction,” “angina pectoris,” and “rheumatoid arthritis.” The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death. Results: A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726–0.876, P = .001, I2 = 27. 9%). Conclusion: MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.

Inflammation in the central nervous system (CNS) contributes to disease pathologies by disrupting the integrity of the blood-brain barrier (BBB). Tight junctions (TJ) are a key component of the BBB. Following hypoxic-ischaemic or mechanical injury to the brain, inflammatory mediators are released such as cytokines, chemokines, and growth factors. Simultaneously, matrix metalloproteinases (MMPs) are released which can degrade TJ proteins. Subsequently, the function and morphology of the BBB are disrupted, which allows immune cells an opportunity to enter into the brain parenchyma. This review summarises the information on the role of TJ protein families in the BBB and provides a comprehensive summary of the mechanisms whereby inflammation breaks down the BBB by increasing degradation of TJ proteins.

Lately, Drosophila has been favored as a model in sleep and circadian rhythm research due to its conserved mechanism and easily manageable operation. These studies have revealed the sophisticated parameters in whole-day sleep profiles of Drosophila, drawing connections between Drosophila sleep and human sleep. In this study, we tested several sleep deprivation protocols (mechanical shakes and light interruptions) on Drosophila and delineated their influences on Drosophila sleep. We applied a daytime light-deprivation protocol (DD) mimicking jet-lag to screen drugs that alleviate sleep deprivation. Characteristically, classical sleep-aid compounds exhibited different forms of influence: phenobarbital and pentobarbital modified total sleep time, while melatonin only shortened the latency to sleep. Such results construct the basis for further research on sleep benefits in other treatments in Drosophila. We screened seven herb extracts, and found very diverse results regarding their effect on sleep regulation. For instance, Panax notoginseng and Withania somnifera extracts displayed potent influence on total sleep time, while Melissa officinalis increased the number of sleep episodes. By comparing these treatments, we were able to rank drug potency in different aspects of sleep regulation. Notably, we also confirmed the presence of sleep difficulties in a Drosophila Alzheimer’s disease (AD) model with an overexpression of human Abeta, and recognized clear differences between the portfolios of drug screening effects in AD flies and in the control group. Overall, potential drug candidates and receipts for sleep problems can be identified separately for normal and AD Drosophila populations, outlining Drosophila’s potential in drug screening tests in other populations if combined with the use of other genetic disease tools.

Most chemotherapeutic drugs commonly suffer from low aqueous solubility that can potentially limit drugs absorption. Drug nanomerization is an advanced approach to overcoming their poor water-solubility. In this study, class I hydrophobin recombinant HGFI (rHGFI)-based curcumin (Cur) nanoparticles (rHGFI-Cur) were prepared by freeze-drying method. The rHGFI-Cur nanocomposites were characterized by contact angle, transmission electron microscopy, fluorescence microscopy and dynamic light scattering. The results showed that rHGFI could lead to the wettability conversion and stability improved of Cur in water. X-ray photoelectron spectroscopy and Fourier transform infrared suggested that rHGFI could non-covalently bind to Cur to render them hydrophilic through hydrophobic forces. Additionally, drug release and cytotoxicity assays illustrated that rHGFI-Cur nanoparticles could facilitate Cur release and exhibited higher cytotoxicity than free Cur for human esophageal cancer cells TE-1. Thus, it suggested that rHGFI has a great potential application for hydrophobic drug delivery without toxicity.[Formula: see text].

Summary Purpose This study aims to analyze sensitivities and polymorphisms of the Bethesda panel markers (BAT25, BAT26, D2S123, D5S346 and D17S250) for microsatellite instability testing in Chinese from Jiangsu Province and their clinical implication. Methods MSI, sensitivity and polymorphism analysis in 541 colorectal cancer (CRC) patients were detected by fragment analysis. Results Five hundred and twenty-five tissue samples and 541 blood samples of the 541 sample pairs were successfully amplified. Thirty-four (6.5%) cases were MSI-high (MSI-H) while 33 (6.3%) and 458 (87.2%) were MSI-low (MSI-L) and microsatellite stable (MSS), respectively. BAT26 (85.3%) exhibited the highest instability followed by BAT25 (82.4%), D2S123 (67.6%), D17S250 (64.7%) and D5S346 (50.0%) in MSI-H cases. The median ages of CRC patients with LS, MSI-H, MSI-L and MSS status were 38–43, 48, 60 and 63, respectively. 75.0%, 44.1%, 12.1% and 7.0% CRC cases were mucinous carcinomas in LS, MSI-H, MSI-L and MSS group, respectively. For D2S123, D17S250 and D5S346, heterozygosity was 80.8%, 74.1% and 57.7% and sizes of polymorphic variation range (PVR) were 207 bp to 234 bp, 140 bp to 169 bp and 109 bp to 137 bp, respectively. For D2S123 and D5S346, there was a bimodal distribution distinguishing the D17S250 from an indistinct trimodal or tetramodal distribution. Conclusion MSI-H cases showed earlier onset and higher proportion of mucinous carcinomas. Mononucleotide BAT26 and BAT25 exhibited higher sensitivity than dinucleotides D2S123, D17S250 and D5S346 in the Chinese population. The dinucleotide markers were highly polymorphic with high percent of heterozygosity, great variation in repeat length and non-normal distribution in Chinese population from Jiangsu Province.

Objective To determine whether early, short-term, low-dose glucocorticoid treatment prevents the progression of severe acute exacerbation of chronic hepatitis B to liver failure. Methods We prospectively enrolled 125 patients with severe acute exacerbation of chronic hepatitis B from the Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University between September 2013 and March 2016. The patients were randomized to a hormone group (3-day, low-dose glucocorticoid treatment plus conventional treatment; 63 patients) and a control group (conventional treatment only; 62 patients). We analyzed markers of liver function, complications, mortality rates, and duration and cost of hospitalization. Results Serum alanine transaminase levels were significantly lower in the hormone group than in the control group at 3 days (P = 0.009) and 1 week (P = 0.018) after treatment. The decrease in this level from the baseline value on day 3 was greater in the hormone group than in the control group (P = 0.023). The trend of the changes in this level significantly differed between the two groups (P = 0.008). The incidence of liver failure (8.06% vs. 30.16%; P = 0.002) and the duration of hospitalization (23.79 vs. 31.79 days; P = 0.031) were significantly lower in the hormone group than in the control group. Conclusion Low-dose, short-term glucocorticoid treatment early in the course of severe acute exacerbation of chronic hepatitis B along with conventional treatment significantly reduced the risk of progression to liver failure and shortened the duration of hospitalization, without increasing the complication rate.

Older patients, especially those with malignancy, may have an increased risk of pulmonary embolism (PE). However, few studies have evaluated the clinical characteristics and prognosis of older patients. We evaluated the clinical characteristics, prognosis, and risk factors in older patients with lung cancer complicated with PE. This was a single-center, prospective cohort study. Older patients (≥65 years) with lung cancer admitted in Beijing Hospital from January 2006 to December 2016 were enrolled. The patients were divided into two groups according to the presence of PE using propensity score matching (PSM). After PSM, one hundred and six patients (53 per group) with an average age of (77.3 ± 10.9) years were enrolled. Adenocarcinoma was the most common histology in patients with PE (52.8%, n = 28), and most lung cancer patients were in stages III and IV (59.4%, n = 63). Patients with PE were stratified to low risk (52.8%, n = 28), intermediate-low risk (24.5%, n = 13), intermediate-high risk (15.1%, n = 8), high-risk (7.5%, n = 4) subgroups. Most PE patients presented with dyspnea (75.5%), and the majority of patients (86.8%, n = 46) developed PE within 3 months after the diagnosis of cancer. The median follow-up time was 23.7 months (12.0–62.0 months), and 7 patients (6.6%) were lost to follow-up. During the follow-up period, 92 patients (86.8%) died, including 8 cases (8.7%) of PE-related death, 73 (79.3%) of tumor death, and 11 (11.9%) of unknown cause. There were significant differences in all-cause mortality (94.3% vs. 83.0%) and PE-related mortality (15.1% vs. 0) between the PE and control groups, but the rate of tumor-related mortality (75.5% vs. 66.0%) was comparable between the groups. Among the 92 patients who died, the mortality rates at 3, 6, 12, and > 12 months after tumor diagnosis were 33.0% (33/106), 57.5% (61/106), 78.3% (83/106), and 89.6% (95/106), respectively. Kaplan–Meier survival analysis showed that the median overall survival time was significantly different between the PE and the control groups (4.3 vs. 9.2 months, P = 0.0015). Multivariate stepwise logistic regression analysis showed that age ≥ 77 years (OR = 2.58, 95%CI: 1.66–4.01), clinical stage III–IV (OR = 2.21, 95%CI: 1.03–4.74), adenocarcinoma (OR = 3.24, 95%CI: 1.75–6.00), high D-dimer (≥600 mg/L) (OR = 2.73, 95%CI: 1.25–5.96), and low partial pressure of oxygen (PaO2; OR = 2.85, 95%CI: 1.74–4.67) were independent risk factors for PE in older patients with lung cancer. Older patients with lung cancer and PE often have poor prognosis. Advanced age, clinical stage III–IV, adenocarcinoma, high D-dimer level, and low PaO2 are independent risk factors for PE.

An 82-year-old woman presented with neck pain and bilateral upper limb paraesthesia after sustaining an unwitnessed fall at home the day before. Physical examination revealed tenderness over the C4-6 region but no evidence of step deformity or neurological deficit. Magnetic resonance imaging of the cervical spine revealed multiple small fractures at the anteroinferior endplate corners of the C3, C5 and C6 vertebrae with focal kyphosis and marrow oedema at these levels, as well as associated disruption of the anterior longitudinal ligament and central spinal canal stenosis. The diagnosis of multiple flexion teardrop fractures was made based on these imaging findings, and the patient subsequently received conservative management. This paper illustrates the radiological features of flexion teardrop fractures and highlights the importance of prompt diagnosis and management of such cases.

Objective: The association between poor intraoperative glycemic control and postoperative acute kidney injury (AKI) in adult cardiac surgery has been observed, but data in the pediatrics remain unknown. We performed a hypothesis that intraoperative hyperglycemia and/or wider glycemic fluctuation were associated with the incidence of postoperative AKI in pediatric cardiac surgery. Methods: A retrospective study was performed in pediatrics who underwent cardiac surgery from 2013 to 2016. Perioperative glycemic data up to 48 hours after surgery were collected and analyzed. Patients with AKI were matched 1:1 with patients without AKI by a propensity score. Variables of demographic data, preoperative renal function and glycemic level, perioperative cardiac condition were matched. Results: The incidence of AKI was 11.5% (118/1026), with 53.4% (63/118), 30.5% (36/118), and 16.1% (19/118) categorized as AKIN stages I, II, and III, respectively. Children who experienced AKI were younger and cyanotic, underwent more complex surgeries, had higher peak intraoperative glucose levels, wider intraoperative glycemic fluctuation, greater inotropic scores and more transfusions, and poor outcomes (all p

Background Gastrointestinal stromal tumors (GISTs) with different types of mutations exhibit different clinical characteristics and prognosis. This study aimed to evaluate the prognostic value of mutations in KIT and PDGFRA in a large‐scale cohort of GIST patients with current therapy including surgery and imatinib. Methods A total of 1163 patients diagnosed with GISTs between January 2006 and December 2018 were enrolled in this study. Mutation analysis was performed for exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA. Mutations were grouped into 12 categories according to the gene, exon, and involved codons; they were analyzed considering the clinical characteristics, disease‐free survival (DFS), and overall survival (OS) of patients with GISTs. Results In low‐risk GISTs, we identified two predictors of worse DFS: tumor origin in the rectum and KIT exon 11 deletion involving two or more codons. In high‐risk GISTs treated with R 0 resection and imatinib, patients with KIT exon 11 homozygous mutations and KIT intron 10/exon 11 junction deletions demonstrated the highest recurrence rate, indicating that these mutations can be independent prognostic factors of DFS. The presence of KIT exon 11 homozygous mutations also independently influenced OS. Conclusion Low‐incidence mutations such as KIT exon 11 homozygous mutations or intron 10/exon 11 junction deletions in GISTs should be carefully evaluated to explore novel treatment strategies, as tumors with these mutations have a high recurrence rate and a very poor prognosis after surgery followed by imatinib adjuvant treatment., Low‐incidence mutations such as KIT exon 11 homozygous mutations or intron 10/exon 11 junction deletions in GISTs should be carefully evaluated to explore novel treatment strategies, as tumors with these mutations have a high recurrence rate and a very poor prognosis after surgery followed by imatinib adjuvant treatment.

Atypical squamous cells of undetermined significance (ASCUS) are the most common cytological abnormality of all smear test. No study has demonstrated the prevalence of cervical cancer or its precursor in Chinese patients with ASCUS. This study aims to investigate the prevalence of cervical intraepithelial neoplasia 1 or worse (CIN1+) and CIN3 or worse (CIN3+) in patients with ASCUS in China to provide insight into appropriate management for Chinese health care. In a retrospective cross-sectional study, patients who underwent liquid-based thin layer cytology and human papillomavirus (HPV) co-testing at the Peking Union Medical College Hospital between January 2014 and January 2017, and had ASCUS results on liquid-based thin layer cytology test and underwent follow-up and colposcopic biopsy were included. Age, HPV DNA test, and pathological outcomes were assessed. One hundred forty-four patients with ASCUS and positive HPV test results were included. In the 3-year follow-up, 23 (16.0%) patients had CIN1, 28 (19.4%) had CIN2, and 17 (11.8%) had CIN3 or carcinoma in situ. The risk of CIN3+ was significantly higher in those older than 60 years (42.8%, P = .005), whereas the CIN1+ prevalence displayed no significant difference between age groups. Both hybrid Capture II (HC II) value and cytopathological description of HPV infection showed no statistically significant correlation with CIN1+ or CIN3+. Patients with HPV-positive ASCUS who were older than 60 years had a significantly higher risk of CIN3+, and clinicians should pay more attention to them. Both HC II value and cytopathological description of HPV infection showed no significant correlation with CIN1+ or CIN3+.

Background Data on visuomotor performance in combat training and the effects of combat training on visuomotor performance are limited. This study aimed to investigate the effects of a specially designed combat sports (CS) training program on the visuomotor performance levels of children. Methods A pre–post comparative design was implemented. A total of 26 students aged 9–12 years underwent 40-min CS training sessions twice a week for 8 weeks during their physical education classes. The CS training program was designed by a karate coach and a motor control specialist. The other 30 students continued their regular activities and were considered as a control group. Each student’s eye movement was monitored using an eye tracker, whereas the motor performance was measured using a target hitting system with a program-controlled microprocessor. The measurements were taken 8 weeks before (baseline), 1 day before (pretest), and 1 week after (posttest) the designated training program. The task used for evaluating these students was hitting or tracking random illuminated targets as rapidly as possible. A two-way analysis of variance [group(2) × time(3)] with repeated measures of time was performed for statistical analysis. Results For the children who received combat training, although the eye response improvement was not significant, both the primary and secondary saccade onset latencies were significantly earlier compared to the children without combat training. Both groups of students exhibited improvement in their hit response times during the target hitting tasks. Conclusion The current finding supported the notion that sports training efforts essentially enhance visuomotor function in children aged 9–12 years, and combat training facilitates an earlier secondary saccade onset.

Pearl is one of the well-known traditional Chinese medicine (TCM) prescribed for treating various skin and bone related disorders due to its abundant proteins and mineral contents. The present investigation focused on antioxidation and life span prolonging effects from different extracts of pearl powder. During in vitro studies, various oxidative indices were evaluated, along with lifespan-prolonging effect were checked using wild-type Caenorhabditis elegans. For the clinical trial, 20 healthy middle-aged subjects were recruited and separated into 2 groups as experimental and placebo group, who received 3 g of pearl powder/d (n = 10) and 3 g of placebo/d (n = 10) for 8 weeks, respectively. During the initial, 2nd, 4th, 6th, 8th and 10th weeks the blood samples were collected for biochemical analysis. The protein extract of pearl powder recorded maximum (p

This study aimed to develop an LC-MS/MS method for determining sildenafil and its metabolites N-desmethylsildenafil and N1,N4-desmethylsildenafil in human plasma and applying it to a pharmacokinetic study of sildenafil in healthy volunteers. Sildenafil-d8 was used as the internal standard. Plasma samples were pretreated via protein precipitation with acetonitrile. The extractives were then separated on an ACQUITY UPLC BEH C18 (50-mm × 2.1-mm, 1.7-μm) column using gradient elution. The aqueous and organic mobile phases were ammonium formate 2 mM supplemented with 0.1% formic acid in water and acetonitrile, respectively, and the flow rate was 0.3 mL/min. An electrospray ionization source was applied, and multiple reaction monitoring was operated in the positive mode with selective channels at m/z 475.30 → 100.10, 461.20 → 283.30, 483.30 → 108.10, and 449.00 → 283.00 for sildenafil, sildenafil-d8, N-desmethylsildenafil, and N1,N4-desmethylsildenafil, respectively. The linear calibration curves of sildenafil and its metabolites spanned 1.0-1000 ng/mL. The lower limit of quantification was 1.0 ng/mL. The extractive recovery of analytes from the biological matrix was more than 90% and the matrix effect complied with relevant provisions. The intra- and inter-day precisions of sildenafil and its metabolite were10%. The intra- and inter-day accuracy of sildenafil, N-desmethylsildenafil, and N1,N4-desmethylsildenafil was more than 99%. The method is highly sensitive and selective, and it was successfully applied to the bioequivalence studies of 100-mg sildenafil citrate tablets in 40 healthy Chinese volunteers.

Toll-like receptor 2 (TLR2) is a pattern recognition receptor which plays an important role in innate immune system. In humans it's encoded by the TLR2 gene and also been designated as CD282. Using CRISPR/Cas9 gene editing technology, we have established a TLR2 mutant WAe001-A-64 cell line from the original embryonic stem cell line H1. It has adopted two biallelic deletions in exon 3 of TLR2 which resulted in a frame shift and early termination in the translation of TLR2. Moreover, WAe001-A-64 has maintained the normal karyotype, pluripotent phenotype, parental cell morphology and the ability to differentiate into three germ layers.

Endometrial-derived stem cells (EnSCs) serve an important role in the development of endometriosis via retrograde menstruation. Abnormal expression of miRNAs in EnSCs is involved in the etiology of endometriosis, however, the mechanisms remain unclear. The aim of the present study was to investigate the expression of miR‑34a‑5p and VEGFA in endometrial samples from patients with or without endometriosis, and then examine the underlying mechanism of microRNA‑34a‑5p regulation of VEGFA in EnSCs. Endometrial samples from patients with or without endometriosis were collected, and miR‑34a‑5p expression in the two groups was measured using RT‑PCR. Human endometrial‑derived stem cells (hEnSCs) were isolated from these endometrial samples, and hEnSCs were transfected with the miR‑34a‑5p mimics or control miRNAs. qPCR and western blotting were performed to assess the effects of miR‑34a‑5p on the expression of VEGFA in hEnSCs, and cell growth was assessed by an MTT assay. miR‑34a‑5p was significantly downregulated in patients with endometriosis when compared with that of those without endometriosis. VEGFA expression levels in hEnSCs with an overexpression of miR‑34a‑5p were significantly reduced when compared with those in the negative control (P

Context: Ganoderma lucidum (Leyss: Fr) Karst. (Polyporaceae) is an oriental medicinal fungus, commonly used in traditional Chinese medicine (TCM) for treating various condition or diseases such as hypertension, hyperglycaemia, hepatitis and cancer. Objective: The current study examines whether triterpenoids and polysaccharide-enriched G. lucidum (GL) influence antioxidation and hepatoprotective efficacy by suppressing oxidative stress. Materials and methods: Forty-two healthy subjects (22 male and 20 female) were recruited and segregated into two groups as experimental or placebo and requested to intake GL (n = 21) or placebo (n = 21) capsule (225 mg; after lunch or dinner) for six consecutive months and vice versa with one month washout period in between. The anthropometric analysis and biochemical assays, as well as abdominal ultrasonic examination were performed. Results: Consumption of GL substantially improved (p

Background Most sporadic gastrointestinal stromal tumors (GISTs) occur as solitary tumors, while multiple sporadic GISTs are extremely rare and often misdiagnosed as metastatic GISTs, leading to inappropriate treatment. This study aimed to investigate the clinicopathological characteristics, diagnostic clues, and prognoses of multiple sporadic GISTs. Methods Twenty-seven patients with multiple sporadic GISTs and 11 patients with metastatic GISTs mimicking sporadic GISTs were analyzed. The clinicopathological characteristics, genetic mutation types, and prognoses were summarized. In addition, 1066 cases of primary GISTs with a single lesion diagnosed at the same hospital were included as controls. Results Compared with 1066 cases of primary GIST with a single lesion, multiple sporadic GISTs occurred at an older age, were more common in women than in men, and were located mainly in the stomach. They were generally small in size, had a low mitotic index and were more often rated as very low risk/low risk. Mutation analysis of all available lesions revealed different KIT/PDGFRA mutation patterns among tumors from the same patients. No patient relapsed during the follow-up period. Among 11 patients with metastatic GISTs that mimicked multiple sporadic GISTs, multiple lesions from the same patient always had concordant pathological and mutational characteristics; namely, they carried an identical KIT/PDGFRA mutation, and the mitotic index was usually high. Conclusions The prognoses of patients with multiple sporadic GISTs were not worse than those of patients with a single lesion of the same risk under the same treatment. When it was difficult to distinguish multiple sporadic GISTs from metastatic GISTs, multiple lesions in the same patient carried different KIT/PDGFRA mutation patterns, which supported tumor multiplicity, while the concordant hypermitotic phase in multiple lesions of GISTs suggested that the tumor was metastatic.

Background Dexmedetomidine is widely used for non-invasive pediatric procedural sedation. However, the hemodynamic effects of intravenous dexmedetomidine are a concern. There has been a growing interest in the application of intranasal dexmedetomidine as a sedative in children. Objective To investigate the incidence of bradycardia in children undergoing intranasal dexmedetomidine sedation and to identify the associated risk factors. Methods Data pertaining to pediatric patients who underwent intranasal dexmedetomidine sedation for non-invasive investigations at the Kunming Children's Hospital between October 2017 and August 2018 were retrospectively analyzed. Results Out of 9984 children who qualified for inclusion, 228 children (2.3%) developed bradycardia. The incidence of bradycardia in the group that received additional dose of dexmedetomidine was higher than that in the group that did not receive additional dose (9.2% vs 16.7%; P = .003). The incidence of bradycardia in males was higher than that in females (2.6% vs 1.8%; P = .007). On multivariate logistic regression, only male gender showed an independent association with the occurrence of bradycardia (odds ratio 1.48; 95% confidence interval 1.11-1.97; P = .008). Conclusions The overall incidence of bradycardia in children after sole use of intranasal dexmedetomidine sedation was 2.3%. Male children showed a 1.48-fold higher risk of bradycardia. However, the blood pressure of the children who developed bradycardia was within the normal range. Simple wake-up can effectively manage bradycardia induced by intranasal dexmedetomidine sedation.

Objective To assess the efficacy and safety of apatinib in the treatment of advanced colorectal cancer(CRC). Methods The clinical data of 16 CRC patients treated with apatinib after failure of prior lines of treatment were retrospectively analyzed in terms of objective response rate,disease control rate,progression-free survival,overall survival,adverse events,and prognostic factors. Results The efficacy was evaluable in 14 patients,among whom the objective response rate was 7.1% and the disease control rate was 50%.The median progression-free survival was 3 months(95%CI=1.57-4.42),and the median overall survival was 6.5 months(95%CI=4.10-8.89).The safety was evaluable in 16 patients,among whom the most common grade 3 adverse events were hypertensinon(37.5%)and proteinuria(25%).No grade 4 adverse event was observed.Multivariate analysis did not show any factor directly related to survival.

To evaluate the correlation between clinical spectrum and therapeutic outcomes and neuropsychological deficits in children with status epilepticus during sleep (SES).The clinical spectrum of patients with SES was defined as follows: status epilepticus of benign childhood epilepsy with centro-temporal spikes (SEBECTs), atypical benign focal epilepsy during childhood (ABFEC), non-idiopathic focal epilepsy (NIFE), and Landau-Kleffner syndrome (LKS). SES cases were divided into 4 groups according to neuropsychological findings before treatment: developmental delay/intellectual disability (DD/ID), cognitive impairment (CI), attention deficit and/or hyperactivity behaviors (AHD), and normal group (NG). The therapeutic outcomes were classified into 3 groups: satisfactory response, recurrence, and seizure control.A total of 39 cases (24 males and 15 females) were recruited, including 3 cases with SEBECTs, 26 with ABFEC, 8 with NIFE [2 with focal cortical dysplasia (FCD)], and 2 with LKS. There were 7 patients in the DD/ID group, 8 in the CI group, 19 in the AHD group, and 5 in the NG group. Neuropsychological outcomes were significantly different among clinical spectrum (P 0.001), and neuropsychological deficits frequently occurred in the ABFEC group or in the NIFE group. Besides, 18 patients in the satisfactory group had satisfactory response to medicine or surgery (2 out of 18 cases with FCD), whereas recurrence was observed at least one session within one year in 16 cases in the recurrence group, and no improvement in spike-wave index and cognition/behavior was noted in 5 patients in the seizure control group, although seizure could be controlled. There were significant differences in therapeutic outcomes among clinical spectrum (P = 0.041), with the worst outcomes in the NIFE group (only 1 out of 8 with satisfactory good response).It is important to categorize patients with SES into epilepsy syndromes, including SEBECTs, ABFPEC, NIFE, and LKS; the clinical spectrum may be a significant determinant to influence the outcomes of SES, including neuropsychological deficits and therapeutic outcomes.

Background/Aims: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. Methods: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model. Results: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b. Conclusion: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC.

The production of megakaryocytes (MKs)—the precursors of blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology., Platelets are blood circulating corpuscles generated from megakaryocytes that initiate wound healing. Here, Moreau et al. describe a way of producing large quantities of megakaryocytes from human pluripotent stem cells in the laboratory, moving us a step closer to manufacturing transfusion products.

Background: In-hospital cardiac arrest (IHCA) is a catastrophic complication for patients while admitted in a medical institution. The outcome of IHCA remains poor, and understanding of the prognostic factors for survival outcome after IHCA is lacking, specifically in an oriental population. Methods: A retrospective observational cohort study of 382 patients with IHCA who required resuscitation was conducted in an urban tertiary hospital in Taiwan. Return of spontaneous circulation (ROSC) and survival to hospital discharge were the primary outcome measures. Results: The incidence of IHCA was 3.25 per 1000 admissions. These patients had a mean age of 67.2 ± 21.7 years and were mostly men (66.5%). The rate of successful ROSC was 66%, and the rate of survival to hospital discharge was 11.8%. A stepwise decrease in ROSC was observed with additional resuscitation efforts. Independent predictors for survival to hospital discharge were being female, a resuscitation duration of 30 minutes), as observed in survival to hospital discharge. Conclusion: Based on data from a single hospital registry in East Asia, a shorter duration of resuscitation was demonstrated to be a predictor of immediate survival with ROSC and survival to hospital discharge.