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Inhibition of hypoxia‐induced cardiomyocyte apoptosis is considered as an important treatment method for ischemic heart diseases, but related drugs are still insufficient. The present study aims to explore the protective function and mechanism of the key Chinese medicine monomer diosmetin (DIOS) on the injury of cardiomyocytes induced by hypoxia. Here, AC16 and HCM‐a cells were treated with 40 μM of DIOS under hypoxic environment and a hypoxic rat model was built to study the role of DIOS. The viability and autophagy of cardiomyocytes were increased, but the apoptosis of cells was suppressed by 40 μM DIOS, under hypoxic environment. Intriguingly, 10 mM 3‐methyladenine, an inhibitor of autophagy, reversed the effect of DIOS on autophagy and apoptosis of the cardiomyocytes under hypoxia. Furthermore, DIOS induced AMP‐activated protein kinase (AMPK) activation and Compound C (5 μM), an AMPK inhibitor, attenuated the inhibition of DIOS on the apoptosis of cardiomyocytes under hypoxia environment. In isoprenaline‐induced hypoxic rats, it was verified that DIOS inhibited apoptosis, accelerated autophagy, and activated AMPKα pathway in vivo. Our findings indicated that DIOS alleviated hypoxia‐induced myocardial apoptosis via inducing the activation of AMPK‐induced autophagy. In summary, the study suggested that DIOS inhibited the apoptosis and induced the autophagy of hypoxia‐induced cardiomyocytes through AMPK activation.

The determination of pH values is essential in many chemical, medical, and environmental monitoring processes, which has been relying on conventional pH meters (glass electrodes) for quantitation and pH test strips for qualitative (or semi-quantitative) assessment. In this work, we demonstrate a smartphone-based pH determination technique, which performs digital image analysis of commercial test strips, particularly the determination of either the dominant wavelength (λd) or complementary wavelength (λc) of the color image. In conjunction with a 3D-printed optical accessory (with a surface light source and a macro lens), the quality of captured images have been warranted, and the quantitation accuracy of 0.05 pH units has been achieved. More importantly, the performance of this smartphone-based pH reading system (namely "Smart-pH-Reader") was validated using multiple real-world samples, as the results are consistent with those determined with a standard pH meter. The Smart-pH-Reader is envisioned to be a simple, portable, and accurate tool for pH determination in the fields of environmental monitoring, medical diagnosis, and beyond.

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

The vortex electromagnetic wave has attracted considerable attentions due to its theoretically infinite and orthogonal orbital angular momentum (OAM) mode characteristics. However, it is very diffi...

The root of Scutellaria baicalensis (Scutellaria Radix) has been used as herbal medicine for years, while its stem and leaf (aerial part) are considered as waste. The water extract from the aerial part of S. baicalensis (named as SBA) being included in the feeding of Siganus fuscescens (grey rabbit fish) has been shown to replace antibiotics in aquaculture with excellent outcome. To strengthen the usage of SBA in fish feeding, the total fish output and its nutritive value were determined here. Feeding the fishes with different doses of SBA for a month, the body length and weight were significantly increased after intake of standard feed containing 1% SBA. In parallel, the expressions of alkaline phosphatase and growth‐related factors in bone, liver, and muscle of 1% SBA‐fed fishes were markedly increased, suggesting the beneficial effects of SBA. The composition of amino acid and fatty acid in fish muscle, after intaking 1% SBA‐containing feed, was altered. In SBA‐fed fish muscle, the amounts of threonine and methionine were increased, while the amount of leucine was decreased, as compared with control group. The amounts of fatty acids, including docosahexaenoic acid, phosphatidylcholine, and phosphatidylethanolamine, were increased in the 1% SBA‐fed fish, while the amounts of triglycerides were decreased. The results indicated the growth‐promoting activity of SBA in an in vivo culture of S. fuscescens, as well as to increase the nutritive values of the muscle. Thus, the re‐cycle of waste products during the farming of S. baicalensis herb in serving as fish feeding should be encouraged., The SBA water extract was added into rabbit fish feeding and fed the rabbit fish in an open sea fish farm for a month. The results indicated that the feeding with 1% SBA extract showed strong growth promotion effect. The amino acid and fatty acid contents in fish muscle with SBA addition were altered. Our investigations showed the growth promotion effect of SBA extract in vivo, as well as its potential effect to alter the nutrients content in fish muscle, which further suggested the application of this waste product of S. baicalensis in fish aquaculture.

Background:. Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors. Methods:. This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors. Results:. The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023–1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958–0.983), fatigue (HR: 1.127, 95% CI: 1.009–1.258), ascites (HR: 1.190, 95% CI: 1.057–1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140–1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291–1.769), heart rate (HR: 1.003, 95% CI: 1.001–1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993–0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008–1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220–1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223–1.690), serum sodium (HR: 0.980, 95% CI: 0.972–0.988), serum albumin (HR: 0.981, 95% CI: 0.971–0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073–1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183–1.614), diabetes (HR: 1.118, 95% CI: 1.010–1.237), stroke (HR: 1.252, 95% CI: 1.121–1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626–0.814), β-blockers (HR: 0.673, 95% CI: 0.588–0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604–0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646–0.965), spironolactone (HR: 0.814, 95% CI: 0.663–0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531–0.733), nitrates (HR: 0.715, 95% CI: 0.631–0.811), and digoxin (HR: 0.579, 95% CI: 0.465–0.721). Conclusions:. The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Fingerprints consist of unique patterns of skin ridges and valleys, and are commonly described by three levels of feature details. Most fingerprint identification systems rely on matching only firs...

Stimulator of interferon genes (STING)-mediated innate immune activation plays a key role in tumor- and self-DNA-elicited antitumor immunity and autoimmunity. However, STING can also suppress tumor immunity and autoimmunity. STING signaling in host nonhematopoietic cells was reported to either protect against or promote graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Host hematopoietic antigen-presenting cells (APCs) play key roles in donor T-cell priming during GVHD initiation. However, how STING regulates host hematopoietic APCs after allo-HCT remains unknown. We utilized murine models of allo-HCT to assess the role of STING in hematopoietic APCs. STING-deficient recipients developed more severe GVHD after major histocompatibility complex-mismatched allo-HCT. Using bone marrow chimeras, we found that STING deficiency in host hematopoietic cells was primarily responsible for exacerbating the disease. Furthermore, STING on host CD11c(+) cells played a dominant role in suppressing allogeneic T-cell responses. Mechanistically, STING deficiency resulted in increased survival, activation, and function of APCs, including macrophages and dendritic cells. Consistently, constitutive activation of STING attenuated the survival, activation, and function of APCs isolated from STING V154M knock-in mice. STING-deficient APCs augmented donor T-cell expansion, chemokine receptor expression, and migration into intestinal tissues, resulting in accelerated/exacerbated GVHD. Using pharmacologic approaches, we demonstrated that systemic administration of a STING agonist (bis-(3′-5′)-cyclic dimeric guanosine monophosphate) to recipient mice before transplantation significantly reduced GVHD mortality. In conclusion, we revealed a novel role of STING in APC activity that dictates T-cell allogeneic responses and validated STING as a potential therapeutic target for controlling GVHD after allo-HCT.

Acute focal cerebral ischemic stroke (IS) is a leading cause of morbidity and mortality worldwide. Acupuncture is an emerging alternative therapy that has been beneficial to acute brain ischemia. However, the underlying protective mechanism of its neuroprotective effect remains unclear. Human original circadian rhythm will be lost after IS, which seriously affects the quality of life and functional recovery of stroke patients. We hypothesize that acupuncture treats IS by regulating the balance of Clock and Bmal1. This study aims to explore the effect of acupuncture at acupoints GV20 and BL23 on neuroprotection and anti-apoptosis in middle cerebral artery occlusion (MCAO) rats and expression of apoptosis and circadian rhythm related proteins. Male Sprague-Dawley (SD) rats were randomly divided into five groups: normal group (Normal), sham model group (Sham MCAO), MCAO model group (MCAO), sham electroacupuncture group (Sham EA) and electroacupuncture group (EA). The MCAO model was prepared by electrocoagulation. The first acupuncture treatment was performed within 2 h after surgery, and then acupuncture therapy was performed on 1st day, 2nd day and 3rd day respectively. After their neurological examination at 72 h of ischemia, the rats from each group were sacrificed. Triphenyltetrazolium chloride (TTC) staining was used to evaluate the brain infarct size. Ultrastructural observation on cerebral ischemic cortex and serum inflammatory cytokines were evaluated. TUNEL staining was used to detect cell apoptosis of brain tissue. The expression levels of proteins Bax, bcl-2, caspase-3, Clock and Bmal1 in the cerebral ischemic region were detected by immunofluorescence staining. Here, we presented evidence that EA at GV20 and BL23 could significantly improve the neurological deficit score and infarct size, and alleviate the cell apoptosis of brain tissue. Moreover, acupuncture treatment upregulated the anti-apoptotic Bcl-2/Bax ratio and reversed the upregulation of caspase-3 following 72-h cerebral ischemia. In addition, the expression levels of circadian proteins Clock and Bmal1 were upregulated in EA group while compared with MCAO group. Our study demonstrated that acupuncture exerted neuroprotective effect against neuronal apoptosis after stroke and the mechanism might be related with regulation of circadian rhythm proteins Clock and Bmal1.

The proinflammatory chemokine interleukin-32 is related to various diseases, including cancer. However, it has never been associated with bladder cancer (BC). To detect whether there is a relationship between the IL-32 gene polymorphisms (rs12934561 C/T and rs28372698 T/A) and BC, the study enrolled 170 non-muscle-invasive bladder cancer (NMIBC) patients, 151 muscle-invasive bladder cancer (MIBC) patients, and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the IL-32 single-nucleotide polymorphism (SNP) genotyping. Statistical analysis was performed using SNPstats online analysis software and SPSS software. Our data revealed that the CC homozygous genotype of rs12934561 in BC patients was significantly higher than that in controls ( P = 0.03 , OR = 1.47 , 95 % CI = 1.04 ‐ 2.08 ), and the percentage of TC genotype carriers was relatively less than that of controls ( P = 0.001 , OR = 0.61 , 95 % CI = 0.45 ‐ 0.82 ). Furthermore, the TT homozygous genotype of rs28372698 was associated with a significantly lower overall survival rate in MIBC patients ( P = 0.028 , OR = 2.77 , 95 % CI = 1.11 ‐ 6.90 ). The IL-32 gene polymorphism rs12934561 might be associated with increased BC risk, and the rs28372698 might participate in the prognosis of BC patients. Therefore, they could be potential forecasting factors for the prognosis of MIBC patients.

Summary Introduction Total psoas muscle area (TPA) can indicate the status of the entire human body's skeletal muscle mass. It has been reported that lower TPA can increase the risk of mortality in critically ill patients. The aim of our study was to evaluate the relationship between TPA and ICU mortality and to compare the performance of Sequential Organ Failure Assessment (SOFA), TPA combined with SOFA and Acute Physiology, Chronic Health Evaluation (APACHE-II) for predicting ICU mortality in critically ill surgical patients. Methods This study was a retrospective observational cohort study with a total of 96 critically ill surgical patients, ages 21–96 years old. Main outcome measures included difficult-to-wean (DTW), operation methods, ICU mortality, ICU stay, APACHE II, sepsis and SOFA. CT-scan assessed the TPA. It is acknowledged that the entire study was completed by Hao-Wei Kou et al. and the data were uploaded from plosone.com . The authors used this data only for secondary analysis. Results The results showed that TPA is a protective factor for ICU mortality (OR: 0.99 95% [0.99, 1.00], P = 0.0269). In addition, when we defined sarcopenia-based TPA, our study showed that sarcopenia increased the risk of ICU mortality (OR:3.73 (1.27, 10.98) P = 0.0167. Furthermore, discrimination of ICU mortality was significantly higher using SOFA (AUROC, 0.7810 [99% CI, 0.6658–0.8962]) than either TPA (AUROC, 0.7023 [99% CI, 0.5552–0.8494]) or APACHE II score (AUROC, 0.7447 [99% CI, 0.6289–0.8604]). Additionally, when we combined TPA with SOFA score, the ROC of TPA + SOFA (AUROC, 0.8647 [99% CI, 0.7881–0.9412]) was the highest when compared to the other three models. Conclusion The relationship between TPA and ICU mortality is negative in critically ill surgical patients. In addition, the combination of TPA and SOFA was the best tool among the three scoring systems in providing significant discriminative ability when predicting ICU mortality in critically ill surgical patients.

Purpose: Application of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with hematologic disorders is limited by the development of GVHD. Separation of GVHD and graft-versus-leukemia (GVL) remains a great challenge in the field. We investigated the contribution of individual pathways involved in the complement cascade in GVH and GVL responses to identify specific targets by which to separate these two processes. Experimental Design: We used multiple preclinical murine and human-to-mouse xenograft models involving allo-HCT recipients lacking components of the alternative pathway (AP) or classical pathway (CP)/lectin pathway (LP) to dissect the role of each individual pathway in GVHD pathogenesis and the GVL effect. For translational purposes, we used the AP-specific complement inhibitor, CR2-fH, which localizes in injured target organs to allow specific blockade of complement activation at sites of inflammation. Results: Complement deposition was evident in intestines of mice and patients with GVHD. In a preclinical setting, ablation of the AP, but not the CP/LP, significantly improved GVHD outcomes. Complement activation through the AP in host hematopoietic cells, and specifically dendritic cells (DC), was required for GVHD progression. AP deficiency in recipients decreased donor T-cell migration and Th1/Th2 differentiation, while increasing the generation of regulatory T cells. This was because of decreased activation and stimulatory activity of recipient DCs in GVHD target organs. Treatment with CR2-fH effectively prevented GVHD while preserving GVL activity. Conclusions: This study highlights the AP as a new therapeutic target to prevent GVHD and tumor relapse after allo-HCT. Targeting the AP by CR2-fH represents a promising therapeutic approach for GVHD treatment.

Background The pathogenesis underlying the alterations of orbital architecture in Graves’ orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO. Methods A total of 35 GO subjects (70 orbits) were subjected to CT scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes. Results No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P < 0.05). Multiple linear regression analysis on parameters including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P < 0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1 and that OM/TOA ratio affected the DNA methylation block than exophthalmometry. Conclusions This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.

The present study aimed to investigate the effects of miR-504 in cervical cancer. Normal and cervical cancer tissue specimens derived from TCGA and GTEx databases were employed to analyze the miR-504 and PAICS (one of potential target gene of miR-504) expression. Kaplan–Meier strategy was applied to analyze the prognostic powers of miR-504 and PAICS. The proliferation, clonogenic ability, invasion, and migration of cervical cancer cells (C-33A and HeLa) were detected using Cell Counting Kit 8, colony formation, and transwell assays. Pearson correlation analysis was used to assess the correlation between miR-504 and PAICS, which was confirmed using luciferase reporter assay. The mRNA and protein levels were detected by qRT-PCR and western blot, respectively. TCGA data revealed that miR-504 expression might be decreased in cervical cancer, which was correlated with unfavorable prognosis. Further experiments exhibited that abnormal miR-504 expression negatively affected malignant cellular behaviors in cervical cancer, including proliferation, colony formation, invasion, and migration. PAICS was identified as a putative target of miR-504, and negatively related with miR-504 expression. PAICS expression was increased in cervical cancer and its high-regulation-induced worse outcomes of patients with cervical cancer. Rescue experiments indicated that PAICS restricted the impacts of miR-504 in cervical cancer cells. Analysis of western blot suggested that overexpression of PAICS overturned the miR-504-induced EMT inactivation. Our observations elucidated that miR-504, acting as a suppressor for the progression of cervical cancer, inhibits cell proliferation, invasion and migration, and mediates EMT via negatively regulating PAICS.

To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS).A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment.Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P0.05). No significant difference was reported among the 4 groups in any specific adverse events (P0.05).HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).

Mikania micrantha Kunth is an invasive alien weed and known as a plant killer around the world. Accurately and rapidly identifying M. micrantha in the wild is important for monitoring its growth status, as this helps management officials to take the necessary steps to devise a comprehensive strategy to control the invasive weed in the identified area. However, this approach still mainly depends on satellite remote sensing and manual inspection. The cost is high and the accuracy rate and efficiency are low. We acquired color images of the monitoring area in the wild environment using an Unmanned Aerial Vehicle (UAV) and proposed a novel network —MmNet— based on a deep Convolutional Neural Network (CNN) to identify M. micrantha in the images. The network consists of AlexNet Local Response Normalization (LRN), along with the GoogLeNet and continuous convolution of VGG inception models. After training and testing, the identification of 400 testing samples by MmNet is very good, with accuracy of 94.50% and time cost of 10.369 s. Moreover, in quantitative comparative analysis, the proposed MmNet not only has high accuracy and efficiency but also simple construction and outstanding repeatability. Compared with recently popular CNNs, MmNet is more suitable for the identification of M. micrantha in the wild. However, to meet the challenge of wild environments, more M. micrantha images need to be acquired for MmNet training. In addition, the classification labels need to be sorted in more detail. Altogether, this research provides some theoretical and scientific basis for the development of intelligent monitoring and early warning systems for M. micrantha and other invasive species.

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

Manganese–zinc (MnZn) power ferrites own significant applications in inductors and transformers for power conversion. The performance of these components is dependent on permeability, saturation induction, core losses, and dc bias superposition characteristics of MnZn ferrites. It is worth emphasizing that excellent dc bias superposition characteristics of ferrites are beneficial for the stability and efficiency of power converters operated with both ac and dc signals. In this paper, Co2O3-doped MnZn ferrites are fabricated using a solid-state reaction method and used to investigate dc bias superposition characteristics of permeability and core losses. More importantly, the physical mechanism of the dc bias superposition characteristics is clarified. Furthermore, the effect of Co2O3 doping on the efficiency of buck circuit was also investigated. The dc bias superposition characteristics suggests potential application in power components and systems.

We report a facil and robust strategy for fabricating flexible piezoelectric nanogenerator based on free-standing polydimethylsiloxane (PDMS) / ZnO nanowire (NW) hybrid film. Free-standing hybrid film was fabricated by mechanical exfoliation of ZnO NWs grown on a FR4 substrate. The free-standing ZnO/PDMS hybrid film is robust enough to be transferred into a flexible substrate of polyimide (Kapton) with Au sputtered. The nanogenerator based on the free-standing hybrid film exhibits stable output voltage about 0.7 V and current of 7 nA under pressing conditions. This facil and robust method should hold significant promise applications in efficient energy harvesting.

The inseparable internet requirements and the endless stream of cyber-attacks have led to strong demand for trusted IP addresses. However, the existing collaborative DNS security schemes have the defects of low credibility and imperfect incentive mechanism. Enlightened by the Consortium blockchain technology, we propose a novel DNS Cache Resources Trusted Sharing Model, which can improve the credibility of DNS resolution results by establishing a complete chain of trust. Firstly, the consortium blockchain is introduced as the carrier of the peer-to-peer network to reduce the impact of illegal access and complicity tampering on the DNS cache credibility; Secondly, the evaluation index of the node credibility in the DNS cache sharing model is proposed, and the trust-based incentive mechanism is designed to reduce the impact of free-riding behavior and on the trusted performance of the system. The two indicators of node abnormal behavior similarity and roundtrip time between nodes are used to comprehensively evaluate the degree of recommendation of the node and serve as the basis for dynamic scheduling; Finally, we use the stochastic distributed decentralized storage mechanism to solve the problem of low efficiency in the consortium blockchain. The simulation results show that the model has certain advantages in ensuring the credibility of domain name resolution results, and maintains the ideal efficiency while ensuring trust.

We analyze the photonic topological phases in bianisotropic metamaterials characterized by a chirality tensor with zero trace. We found that the strength of chirality component determines the topological character of the metamaterial. The underlying medium can be considered as a topological semimetal with the nontrivial band gap in the momentum space. The topological properties are described by the spin-orbit Hamiltonians with spin 1 and characterized by the nonzero topological invariants. In particular, photonic quantum Hall states exist when the longitudinal chirality component exceeds the permittivity, whereas photonic quantum spin Hall states are present when the chiral nihility occurs. Considering the dispersion in the frequency domain, the bianisotropic metamaterial is regarded as a photonic Weyl system that supports the Weyl points and Fermi arcs. The topological features are further illustrated with the robust transport of edge states at an irregular boundary of the metamaterial.

Background: This study aims to compare whether 2 different routes of renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. Methods: Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n = 6) or a hypertension model group (high-fat diet, n = 18). The model group was randomly divided into the intima-RDN group (n = 6), the adventitia-RDN group (n = 6), or the renal arteriography-only group (sham group, n = 6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin staining and Masson staining; superoxide dismutase activity and the malondialdehyde content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-β 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Smad3 was assessed by Western blot, and electron microscopy was used to examine changes in the kidney microstructure. Results: After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed p < 0.05); the blood lipid levels of the control group did not change significantly from baseline (p > 0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (p < 0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. Conclusion: RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high-fat-induced renal fibrosis. The antifibrotic effect of RDN may be related to inhibition of the TGF-β1/Smad3 pathway.

Background Little is known about chronic cannabis smoking-associated oral microbiome and its effects on central nervous system (CNS) functions. Methods In the current study, we have analyzed the saliva microbiome in individuals who chronically smoked cannabis with cannabis use disorder (n = 16) and in non-smoking controls (n = 27). The saliva microbiome was analyzed using microbial 16S rRNA sequencing. To investigate the function of cannabis use-associated oral microbiome, mice were orally inoculated with live Actinomyces meyeri, Actinomyces odontolyticus, or Neisseria elongata twice per week for six months, which mimicked human conditions. Findings We found that cannabis smoking in humans was associated with oral microbial dysbiosis. The most increased oral bacteria were Streptococcus and Actinomyces genus and the most decreased bacteria were Neisseria genus in chronic cannabis smokers compared to those in non-smokers. Among the distinct species bacteria in cannabis smokers, the enrichment of Actinomyces meyeri was inversely associated with the age of first cannabis smoking. Strikingly, oral exposure of Actinomyces meyeri, an oral pathobiont, but not the other two control bacteria, decreased global activity, increased macrophage infiltration, and increased β-amyloid 42 protein production in the mouse brains. Interpretation This is the first study to reveal that long-term oral cannabis exposure is associated oral enrichment of Actinomyces meyeri and its contributions to CNS abnormalities.

Qingsong Wang,1 Xiu-ling Zhou,2 Guang-hai Mei,3 Jiantao Wang,1 Zhongyu Yu,1 Yue Hu,1 Xinyu Guo,1 Hanyu Zhang,1 Xiaodie Xu,4 Chengfeng He,4 Jingchun Guo,4 Yinghong Tao,5 Houguang Zhou1 1Department of Geriatrics, Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Ultrasonics, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Key Laboratory of Medical Neurobiology, Institute of Brain Science, Fudan University, Shanghai, 200030, People’s Republic of China; 5Department of Medical Examination Center, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Houguang ZhouDepartment of Geriatrics of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, No. 24 Ward, Building 6, No.12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52887246Email zhouhouguang@huashan.org.cnYinghong TaoDepartment of Medical Examination Center of Huashan Hospital, Fudan University, Building 4, No. 12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52889087Email taoyinghong@huashan.org.cnAim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected.Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05).Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.Keywords: metabolic inflammatory syndrome, MIS, heparanase, HPA, C-reactive protein, CRP, interleukin-6, IL-6, chronic low-grade inflammation, CLGI

A magnetic dipole quasi-Yagi antenna based on a dielectric resonator (DR) is proposed in this letter. The dominate TE1δ1 mode of the rectangular DR is used as a magnetic dipole which can be differentially fed by the coplanar strip line (CPS). Thanks to the DR employment, the proposed antenna has several advantages such as compact size and flexible design which means the 3-D dimensions of the DR can be easily adjusted to cater for various applications. Meanwhile, the gain of the proposed DR quasi-Yagi antenna is higher than that of traditional electric dipole counterparts. Furthermore, since the DR driver is horizontally polarized, both the metal strip and DR can be used as a director for enhancing the end-fire gain. To verify the design concept, a prototype operating at the X-band is fabricated and measured. Good agreement between the simulated and measured results can be observed.

Oxidative stress is elevated in the recipients of allogeneic hematopoietic transplantation (allo-HCT) and likely contributes to the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production and migration of alloreactive donor T cells, and remains a major cause of morbidity and mortality after allo-HCT. Hence, strategies to limit oxidative stress in GVHD are highly desirable. Thioredoxin1 (Trx1) counteracts oxidative stress by scavenging reactive oxygen species (ROS) and regulating other enzymes that metabolize H2O2. The present study sought to elucidate the role of Trx1 in the pathophysiology of GVHD. Using murine and xenograft models of allogeneic bone marrow transplantation (allo-BMT) and genetic (human Trx1-transgenic, Trx1-Tg) as well as pharmacologic (human recombinant Trx1, RTrx1) strategies; we found that Trx1-Tg donor T cells or administration of the recipients with RTrx1 significantly reduced GVHD severity. Mechanistically, we observed RTrx1 reduced ROS accumulation and cytokine production of mouse and human T cells in response to alloantigen stimulation in vitro. In allo-BMT settings, we found that Trx1-Tg or RTrx1 decreased downstream signaling molecules including NFκB activation and T-bet expression, and reduced proliferation, IFN-γ production and ROS accumulation in donor T cells within GVHD target organs. More importantly, administration of RTrx1 did not impair the graft-versus-leukemia (GVL) effect. Taken together, the current work provides a strong rationale and demonstrates feasibility to target the ROS pathway, which can be readily translated into clinic.

Simple obesity is a worldwide epidemic associated with rapidly growing morbidity and mortality which imposes an enormous burden on individual and public health. As a part of Traditional Chinese Medicine (TCM), acupuncture has shown the positive efficacy in the management of simple obesity. In this article, we comprehensively review the clinical and animal studies that demonstrated the potential mechanisms of acupuncture treatment for simple obesity. Clinical studies suggested that acupuncture regulates endocrine system, promotes digestion, attenuates oxidative stress, and modulates relevant molecules of metabolism in patients of simple obesity. Evidence from laboratory indicated that acupuncture regulates lipid metabolism, modulates inflammatory responses, and promotes white adipose tissue browning. Acupuncture also suppresses appetite through regulating appetite regulatory hormones and the downstream signaling pathway. The evidence from clinical and animal studies indicates that acupuncture induces multifaceted regulation through complex mechanisms and moreover a single factor may not be enough to explain the beneficial effects against simple obesity.

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. The development of novel ABCG2 inhibitors has emerged as a tractable strategy to circumvent drug resistance. In this study, an ABCG2-knockout colorectal cancer cell line was established to assist inhibitor screening. Additionally, we found that ataxia-telangiectasia mutated (ATM) kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to ABCG2 substrate chemotherapeutic drugs mitoxantrone and doxorubicin by retaining them inside cells. Western blot assay showed that AZ32 did not alter the expression of ABCG2. Moreover, molecule docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2. In conclusion, our result demonstrated that AZ32 could potently reverse ABCG2-mediated MDR in colorectal cancer.

IL-12 (p35/p40) and IL-23 (p19/p40) signal through IL-12R (IL-12Rβ2/β1) and IL-23R (IL-23Rα/IL-12Rβ1), respectively, which can promote pathogenic T lymphocyte activation, differentiation, and function in graft-versus-host disease (GVHD). With the use of murine models of allogeneic hematopoietic cell transplantation (HCT), we found that IL-12Rβ1 on donor T cells was dispensable to induce acute GVHD development in certain circumstances, while IL-23Rα was commonly required. This observation challenges the current paradigm regarding IL-12Rβ1 as a prerequisite to transmit IL-23 signaling. We hypothesized that p19/EBI3 (IL-39) may have an important role during acute GVHD. With the use of gene transfection and immunoprecipitation approaches, we verified that p19 and EBI3 can form biological heterodimers. We found that IL-39 levels in recipient serum positively correlated with development of acute GVHD in experimental models and in clinical settings, thereby implicating IL-39 in the pathogenesis of acute GVHD. Furthermore, we observed that human T cells can signal in response to IL-39. In chronic GVHD, IL-23Rα and IL-12Rβ1 were similarly required for donor T cell pathogenicity, and IL-39 levels were not significantly different from controls without GVHD. Collectively, we identify a novel cytokine, IL-39, as a pathogenic factor in acute GVHD, which represents a novel potential therapeutic target to control GVHD and other inflammatory disorders.

Debate on the effectiveness of preoperative embolization for spinal metastatic lesions, especially for nonhypervascular tumors, has persisted. The present study aimed to identify the effectiveness of preoperative embolization in patients who had undergone surgery for spinal metastasis.Two of us (Z.T. and Z.H.) independently searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases to identify eligible clinical studies that had compared the outcomes of patients treated surgically for spinal metastatic disease with or without preoperative embolization. The primary outcomes included intraoperative blood loss, perioperative blood loss, and transfusion requirements. The secondary outcomes include the operative time, overall survival, and complication rates. Meta-analyses were performed for subgroups of hypervascular, nonhypervascular, and mixed tumors. A fixed effects model was applied when IA total of 12 studies (1 randomized controlled trial and 11 retrospective case-control studies), with 744 patients, were included. Significantly less intraoperative blood loss (mean difference [MD], -1171.49 mL; 95% confidence interval [CI], -2283.10 to -59.88; P = 0.039), fewer blood transfusions (MD, -3.13 U; 95% CI, -4.86 to -1.39; P 0.001), and shorter operative times (MD, -33.91 minutes; 95% CI, -59.65 to -8.17; P = 0.010) were identified for the embolization group in the hypervascular subgroup. In the nonhypervascular and mixed tumor subgroups, no differences in effectiveness were identified in blood loss, transfusion requirement, or operative time when stratified by the use of embolization. The overall survival and complication rates were similar between the embolization and nonembolization groups in each subgroup.The current data support the use of preoperative embolization for hypervascular metastatic tumors to the spine. However, little evidence is available to support the use of preoperative embolization for nonhypervascular metastatic tumors to the spine.

We investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients.The sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys.DnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell-mediated rejection (p 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p 0.05).DnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.

BackgroundBreast cancer is the most common malignant tumor in women. Due to the mechanism of breast cancer has not yet been completely clear, we aim to identify the key pathway and genes in breast cancer based on bioinformatics method. MethodsThe samples were obtained from NCBI-GEO website. Then, GEO2R tools and Venn diagram software were used to identify the differentially expressed genes (DEGs). Gene enrichment analysis was performed by ClusterProfiler package (version 3.16.1) of R. The protein-protein interaction (PPI) network was plotted by Search Tool for the Retrieval of Interacting Genes (STRING) website and candidate genes were selected from PPI network by Molecular Complex Detection (MCODE) plug-in. Afterwards, we assess the overall survival and expression level of the core genes by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Finally, we selected the core genes through the analysis of different grades cancer and analyzed the gene-drug interaction by Comparative Toxicogenomics Database (CTD).ResultsDEGs contained 23 up-regulated and 32 down-regulated genes. GO described biological process, cellular component, and molecular function. KEGG analysis showed up-regulated DEGs were mainly involved in breast cancer-related pathway like P53 signaling pathway, platinum drug resistance and bladder cancer. 15 candidate genes were screened through PPI network, 14 of which had adverse prognosis and high expression in breast cancer. At last, we selected 5 core genes from different grades analysis and found the interaction of these genes and anthracyclines and cyclophosphamide.ConclusionsIn the current study, 5 core genes of breast cancer were identified based on bioinformatics method, which could useful to provide essential information for diagnosis, prognosis and treatment of breast cancer.

To evaluate the prognostic effect of pre-treatment factors in patients with spinal metastases secondary to lung cancer, and establish a novel predicting nomogram for predicting the survival probability.A total of 209 patients operated for spinal metastases from lung cancer were consecutively enrolled, and divided into the training and validation samples with a ratio of 7:3, for model establishing and validating, respectively. Basing on the training sample, univariate and multivariate COX proportional hazard models were used for identifying the prognostic effect of pre-treatment factors, following which significant prognostic factors would be listed as items in nomogram to calculate the survival probabilities at 3, 6, 12 and 18 months. Then, the C-indexes and the calibration curves would be figured out to evaluate the discrimination ability and accuracy of the model both for the training and validation samples.In the multivariate COX analysis, the gender, smoking history, location of spinal metastasis, visceral metastasis, Karnofsky performance status (KPS), adjuvant therapy, lymphocyte percentage and globulin were found to be significantly associated with the overall survival, and a novel nomogram was generated basing on these independent predictors. The C-indexes for the training and validation samples were 0.761 and 0.732, respectively. Favorable consistencies between the predicted and actual survival rates were demonstrated both in the internal and external validations.Pre-treatment characteristics, including gender, smoking history, location of spinal metastasis, visceral metastasis, KPS, adjuvant therapy, percentage of lymphocyte, and serum globulin level, were identified to be significantly associated with overall survival of patients living with spinal metastases derived from lung cancer, and a user-friendly nomogram was established using these independent predictors.

Background The presence or absence of human leukocyte antigen (HLA) antibodies, especially the strength of donor‐specific HLA antibodies (DSAs), has important roles in clinical evaluation and diagnostic decision‐making for solid‐organ transplantation. Dilution patterns help to give a new sight of HLA epitopes. “Epitope matching” is likely to lower the risk of developing DSA and increase the likelihood of matching a compatible donor. Methods We collected data evaluating HLA antibodies with a titration study using mean fluorescence intensity. Results Diluting the serum of recipients can reduce potential inhibitory effects, accurately evaluate the intensity of donor‐specific HLA antibodies, and guide surgeons to take or not take intervention measures. Dilution patterns also help to give a new sight of HLA epitopes. Conclusion We believe that from the viewpoint of HLA antibodies, the dilution model can provide new tools and insights for the study of HLA epitopes.

Peptides have shown great potential in cancer treatment due to their good biocompatibility and low toxicity. However, the bioavailability and adverse immune response of peptides limit their further translation from bench to bedside. Over the past few decades, various peptide-based nanomaterials have been developed for drug delivery and cancer treatment. Compared with therapeutic peptides alone, self-assembled peptide nanomaterials have obvious advantages, such as improved stability and biodistribution for high-performance cancer therapy. In this review, we have described the synthesis, self-assembly and the anti-cancer application of therapeutic peptides and their conjugates, particularly polymer-peptide conjugates (PPCs).

ABO-incompatible (ABO-i) liver transplantation (LT) is a life-saving method for pediatric patients in emergency situations that has the potential to expand the pool of liver donors. However, the risks of ABO-i compared to ABO-compatible (ABO-c) LT are unclear. To address this clinical uncertainty, we conducted a systematic review and meta-analysis to compare clinical outcomes between ABO-i and ABO-c LT in pediatric patients. A systematic search for studies comparing outcomes between ABO-i and ABO-c LT was performed in the MEDLINE (PubMed), EMBASE, and Cochrane Library databases through May 2020. Outcomes evaluated included graft survival rate, patient survival rate, rejection, infection, biliary complications, and vascular complications. Quality of evidence was assessed using the Newcastle–Ottawa scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3. A total of 12 studies involving 7461 patients were included in the review. Meta-analysis of these studies showed significantly lower 1 year, 3 year, and 5 year graft survival rates for ABO-i vs. ABO-c LT (1 year: OR = 0.46, 95% CI 0.35–0.59, P

Renjun Lv,1– 5 Shanjing Nie,1– 4 Zhenhua Liu,6 Yunliang Guo,1– 4 Yue Zhang,7 Song Xu,1– 4 Xunyao Hou,1– 4 Jian Chen,1– 4 Yingjuan Ma,8 Zhongyu Fan,1– 5 Xueping Liu1– 4 1Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 2Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 3Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 4Department of Anti-Aging, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 5Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, Shandong, People’s Republic of China; 6Center of Sleep Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, People’s Republic of China; 7Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, People’s Republic of China; 8Department of Otolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Xueping Liu Tel +86-53168777165Email Liuxueping1962@163.comAim: Obstructive sleep apnea syndrome (OSAS) is a prevalent chronic disease characterized by sleep fragmentation and intermittent hypoxemia. Several studies suggested that electrophysiological changes and neurocognitive abnormalities occurred in OSAS patients. In this study, we compared automatic processing of emotional facial expressions schematic in OSAS patients and matched healthy controls via assessing expression-related mismatch negativity (EMMN).Methods: Twenty-two OSAS patients (mean age 44.59 years) and twenty-one healthy controls (mean age 42.71 years) were enrolled in this study. All participants underwent Montreal Cognitive Assessment (MoCA) scale test and polysomnographic recording. An expression-related oddball paradigm was used to elicit EMMN and the electroencephalogram was recorded and analyzed. Furthermore, Pearson’s correlations were calculated to discuss the correlation between neuropsychological test scores, clinical variables and electrophysiological data.Results: Compared with healthy controls, OSAS sufferers demonstrated significantly reduced EMMN mean amplitudes within corresponding time intervals, regardless of happy or sad conditions. Meanwhile, we observed that amplitude of sad EMMN was larger (more negative) than happy EMNN in healthy controls, while not in patients. Moderate correlations were found between MoCA test scores, sleep parameters and EMMN amplitudes.Conclusion: Our findings suggested pre-attentive dysfunction of processing emotional facial expressions in patients with OSAS, without the existence of negative bias effect. Moreover, correlation analysis showed that clinical characteristics of OSAS patients could affect EMMN amplitudes. Further studies on the advantages of EMMN as clinical and electrophysiological indicators of OSAS are warranted.Keywords: OSAS, EMMN, facial expressions, pre-attentive processing, negative bias effect

Testosterone replacement therapy (TRT) is the primary treatment for male testosterone deficiency. This therapy raises concerns over the risk of prostate cancer (PC), because testosterone has historically been considered the fuel for PC. We discuss the re-evaluation of the relationship between androgen and PC, and highlight the safety of TRT in the treatment of symptomatic men with testosterone deficiency who have low-risk disease after treatment for localized PC with surgery or radiation. Furthermore, we review the clinical application and potential mechanisms of bipolar androgen therapy (BAT) in the treatment of castration-resistant PC, emphasizing that much remains to be done before BAT can be broadly applied.

In order to find the best wireless communication technology scheme for the wireless channel environment between ships on the sea surface, this paper presents a communication model for multipath between ships on the surface of the sea based on the ray tracing algorithm. The multipath model presented herein covers the direct and specular reflection and the diffuse components. In this paper, large-scale fading analyses on wireless channel of ship-to-ship communication are presented.

With the popularization of wireless networks, wireless positioning technology services have met people's positioning needs. How to reduce the cost and improve accuracy of positioning technology is very important. In complex urban environments, network-centric-warfare requires large-scale, portable and inexpensive devices for situational awareness of non-cooperative target sources. In this paper, a fingerprint location algorithm based on KNN classification algorithm is designed and validated. Ray-tracing based channel loss model is adopted in this algorithm for collecting fingerprint database instead of manual collection. Finally, the accuracy of the algorithm is verified by experiment data. The results show that the fingerprint database built with deterministic loss propagation model has a high positioning accuracy.

Background To guide the selection of treatments for spinal metastases, the expected survival time is one of the most important determinants. Few scoring systems are fully applicable for spinal metastasis secondary to prostate cancer (PCa). This study aimed to identify the independent factors to predict the overall survival (OS) of patients with spinal metastases from PCa. Methods The PubMed, Embase and CENTRAL were retrieved by two reviewers independently, to identify studies analyzed the prognostic effect of different factors in spinal metastasis from PCa. A systematic review and quantitative meta-analysis was conducted with hazard ratio (HR) and 95% confidence interval (95%CI) as the effect size. Results A total of 12 retrospective cohort studies (1566 patients) were eligible for qualitative synthesis and 10 for quantitative meta-analyses. The OS was significantly influenced by performance status, visceral metastasis, ambulatory status and time from PCa diagnosis in more than half of the available studies. The meta-analyses demonstrated that OS was significantly influenced by visceral metastasis (HR = 2.24, 95%CI:1.53–3.27, p p p p p = 0.018), time developing motor deficit (HR = 1.57, 95%CI:1.30–1.88, p p Conclusions Visceral metastasis, ambulatory status, extraspinal bone metastasis, performance status, time developing motor deficit and time interval from primary tumor diagnosis were significantly associated with the OS for spinal metastasis from PCa. When selecting the treatment modality, clinicians should fully consider the patients’ systematic status based on all potential prognostic factors. Level of evidence I Meta-analysis.

There is no satisfactory answer on the specific biomarker that might be used in differentiating heart failure with reduced EF (HFrEF), allowing for inadequacy of N-terminal prohormone brain natriuretic peptide (NT-proBNP).We aim to evaluate the value of microRNA-208a in diagnosing HFrEF patients.We included 120 HF patients and 60 healthy volunteers. Diagnostic values of NT-proBNP and miR-208a for HF patients versus controls and HFrEF versus HFpEF were described by area under curve (AUC), sensitivity and specificity.HFrEF patients had significantly higher miR-208a level (p0.001). As for diagnosing HFrEF patients, additional use of miR-208a and NT-proBNP yielded a significantly higher AUC than NT-proBNP alone (0.83, 95% CI 0.76-0.90 vs. 0.73, 95% CI 0.64-0.82) and the sensitivity and specificity were raised to 68.0% and 90.2%.Use of miR-208a in combination with NT-proBNP may allow a more reliable method in diagnosing HFrEF patients.

Background: Early-stage diagnosis and treatment can improve survival rates of liver cancer patients. Dynamic contrast-enhanced MRI provides the most comprehensive information for differential diagnosis of liver tumors. However, MRI diagnosis is affected by subjective experience, so deep learning may supply a new diagnostic strategy. We used convolutional neural networks (CNNs) to develop a deep learning system (DLS) to classify liver tumors based on enhanced MR images, unenhanced MR images, and clinical data including text and laboratory test results. Methods: Using data from 1,210 patients with liver tumors (N = 31,608 images), we trained CNNs to get seven-way classifiers, binary classifiers, and three-way malignancy-classifiers (Model A-Model G). Models were validated in an external independent extended cohort of 201 patients (N = 6,816 images). The area under receiver operating characteristic (ROC) curve (AUC) were compared across different models. We also compared the sensitivity and specificity of models with the performance of three experienced radiologists. Results: Deep learning achieves a performance on par with three experienced radiologists on classifying liver tumors in seven categories. Using only unenhanced images, CNN performs well in distinguishing malignant from benign liver tumors (AUC, 0.946; 95% CI 0.914–0.979 vs. 0.951; 0.919–0.982, P = 0.664). New CNN combining unenhanced images with clinical data greatly improved the performance of classifying malignancies as hepatocellular carcinoma (AUC, 0.985; 95% CI 0.960–1.000), metastatic tumors (0.998; 0.989–1.000), and other primary malignancies (0.963; 0.896–1.000), and the agreement with pathology was 91.9%.These models mined diagnostic information in unenhanced images and clinical data by deep-neural-network, which were different to previous methods that utilized enhanced images. The sensitivity and specificity of almost every category in these models reached the same high level compared to three experienced radiologists. Conclusion: Trained with data in various acquisition conditions, DLS that integrated these models could be used as an accurate and time-saving assisted-diagnostic strategy for liver tumors in clinical settings, even in the absence of contrast agents. DLS therefore has the potential to avoid contrast-related side effects and reduce economic costs associated with current standard MRI inspection practices for liver tumor patients.