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Abstract Background A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time. Methods Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire. Results Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH. Conclusion The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due to its cross-reactivity to RGMc/hemojuvelin, ABT-207 causes iron accumulation in vivo, which could present a safety liability. Here we report the generation and characterization of a novel RGMa-selective anti-N-RGMa antibody elezanumab, which is currently under Phase 2 clinical evaluation in multiple disease indications. Elezanumab, a human monoclonal antibody generated by in vitro PROfusion mRNA display technology, competes with ABT-207 in binding to N-RGMa but lacks RGMc cross-reactivity with no impact on iron metabolism. It neutralizes repulsive activity of soluble RGMa in vitro and blocks membrane RGMa mediated BMP signaling. In the optic nerve crush and optic neuritis models, elezanumab promotes axonal regeneration and prevents retinal nerve fiber layer degeneration. In the spinal targeted experimental autoimmune encephalomyelitis (EAE) model, elezanumab promotes axonal regeneration and remyelination, decreases inflammatory lesion area and improves functional recovery. Finally, in the mouse cuprizone model, elezanumab reduces demyelination, which is consistent with its inhibitory effect on BMP signaling. Taken together, these preclinical data demonstrate that elezanumab has neuroregenerative and neuroprotective activities without impact on iron metabolism, thus providing a compelling rationale for its clinical development in neurodegenerative diseases.

With the aim of extracting the pion charge radius, we analyse extant precise pion+electron elastic scattering data on Q2∈[0.015,0.144] GeV2 using a method based on interpolation via continued fractions augmented by statistical sampling. The scheme avoids any assumptions on the form of function used for the representation of data and subsequent extrapolation onto Q2≃0. Combining results obtained from the two available data sets, we obtain rπ=0.640(7) fm, a value 2.4σ below today's commonly quoted average. The tension may be relieved by collection and similar analysis of new precise data that densely cover a domain which reaches well below Q2=0.015 GeV2. Considering available kaon+electron elastic scattering data sets, our analysis reveals that they contain insufficient information to extract an objective result for the charged-kaon radius, rK. New data with much improved precision, low-Q2 reach and coverage are necessary before a sound result for rK can be recorded.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aimed to identify a potent compound against EGFR-driven tumor. We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects. Cinobufagin also strongly inhibited the proliferation of carcinoma cell lines with wild-type or mutant EGFR expression. In contrast, the compound only weakly inhibited the proliferation of cancer cells with low or without EGFR expression. Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells. In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors. Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.

Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named “ion induction and deduction” was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple “net-hubs” and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.

Using a systematic, symmetry-preserving continuum approach to the Standard Model strong-interaction bound-state problem, we deliver parameter-free predictions for all semileptonic Bc→ηc,J/ψ transition form factors on the complete domains of empirically accessible momentum transfers. Working with branching fractions calculated therefrom, the following values of the ratios for τ over μ final states are obtained: Rηc=0.313(22) and RJ/ψ=0.242(47). Combined with other recent results, our analysis confirms a 2σ discrepancy between the Standard Model prediction for RJ/ψ and the single available experimental result.

Spinal cord injury (SCI) is a devastating condition characterized by loss of function, secondary to damaged spinal neurons, disrupted axonal connections, and myelin loss. Spontaneous recovery is limited, and there are no approved pharmaceutical treatments to reduce ongoing damage or promote repair. Repulsive guidance molecule A (RGMa) is upregulated following injury to the central nervous system (CNS), where it is believed to induce neuronal apoptosis and inhibit axonal growth and remyelination. We evaluated elezanumab, a human anti-RGMa monoclonal antibody, in a novel, newly characterized non-human primate (NHP) hemicompression model of thoracic SCI. Systemic intravenous (IV) administration of elezanumab over 6 months was well tolerated and associated with significant improvements in locomotor function. Treatment of animals for 16 weeks with a continuous intrathecal infusion of elezanumab below the lesion was not efficacious. IV elezanumab improved microstructural integrity of extralesional tissue as reflected by higher fractional anisotropy and magnetization transfer ratios in treated vs. untreated animals. IV elezanumab also reduced SCI-induced increases in soluble RGMa in cerebrospinal fluid, and membrane bound RGMa rostral and caudal to the lesion. Anterograde tracing of the corticospinal tract (CST) from the contralesional motor cortex following 20 weeks of IV elezanumab revealed a significant increase in the density of CST fibers emerging from the ipsilesional CST into the medial/ventral gray matter. There was a significant sprouting of serotonergic (5-HT) fibers rostral to the injury and in the ventral horn of lower thoracic regions. These data demonstrate that 6 months of intermittent IV administration of elezanumab, beginning within 24 h after a thoracic SCI, promotes neuroprotection and neuroplasticity of key descending pathways involved in locomotion. These findings emphasize the mechanisms leading to improved recovery of neuromotor functions with elezanumab in acute SCI in NHPs.

Balanced time perspective refers to the ability to flexibly switch between different temporal foci in an adaptive manner according to the current context. Functional connectivity within the default mode network (DMN) has been suggested to support balanced time perspective. The coupling between the DMN and fronto-parietal network (FPN) may drive many important expressions of internally directed cognition. However, it remains unclear whether balanced time perspective is supported by the interaction between the FPN and DMN. To examine these issues, we recruited 91 participants (52 males with mean age of 19.6, and 39 females with mean age of 20.0) to undergo resting-state brain imaging scan and to complete a questionnaire measuring balanced time perspective. Seed-based voxel-wise functional connectivity analyses implicated midline DMN regions including the anterior medial prefrontal cortex (amPFC) and posterior cingulate cortex (PCC) along with the anterior cingulate cortex (ACC), precuneus, and cerebellum in supporting a balanced time perspective. More importantly, functional connectivity between the right amPFC and right dorsal lateral prefrontal cortex (DLPFC) in the FPN was found to associate with balanced time perspective. Our findings suggest the importance of coordinated brain activity in supporting a balanced time perspective.

Objective: The aim of this study was to measure both plasma and cerebrospinal fluid (CSF) TAR DNA-binding protein 43 (TDP-43) and phosphorylated TDP-43 (pTDP-43) levels in sporadic amyotrophic lateral sclerosis (sALS) patients, and to compare them with that of healthy controls. The correlation between plasma or CSF TDP-43/pTDP-43 and clinical indicators of ALS patients was assessed.Methods: Paired plasma and CSF TDP-43/pTDP-43 levels in 69 ALS patients and 59 healthy controls were measured by sandwich ELISA. Time to generalization (TTG), an indicator suggested that the time of symptoms spreading from spinal or bulbar localization to both, was evaluated in all patients screened for mutations in genes associated with ALS.Results: Both of the plasma TDP-43 and pTDP-43 levels were significantly higher in ALS patients than HCs (P < 0.001). The pTDP-43/TDP-43 ratios in plasma were significantly higher in HCs than ALS patients (P < 0.001). The area under the curve (AUC) value was 0.924 for plasma TDP-43 level, with a 91.3% sensitivity and 91.5% specificity. Moreover, the correlation between plasma and CSF TDP-43 was observed in each ALS patient (r = 0.195, P = 0.027). A correlation between CSF pTDP-43 levels and the ALSFRS-R (r = −0.245; P = 0.042) was established. A correlation was observed between plasma TDP-43 levels and TTG in ALS patients, which indicated that high levels of plasma TDP-43 correlated with prolonged TTG (r = 0.415; P = 0.004).Conclusion: The plasma TDP-43 and pTDP-43 levels might play an important role in diagnosis in the future study of ALS. The plasma TDP-43 might differentiate ALS and HC groups based on high sensitivity and specificity, and as an indicator of progression of disease.

Deaths due to invasive fungal disease (IFD) have been increasing every year. Early and rapid detection is important to reduce the mortality rate associated with IFD. In this study, we explored a novel diagnostic method for detecting IFD, which involves the G Factor α subunit (GFαSub) from Limulus polyphemus. The GFαSub double-sandwich method was developed to detect (1,3)-β-D-glucans in human serum using purified GFαSub and horseradish peroxidase-labeled GFαSub. The GFαSub double-sandwich method and the G test were performed and compared. Using GFαSub sequence analysis, the expression plasmid pET30a-GFαSub252-668 was synthesized, and GFαSub252-668 was expressed and purified via isopropyl-β-d-thiogalactoside induction and nickel-nitrilotriacetic acid affinity. The optimization method was established via the orthogonal method. Using this method, the sera of 36 patients with IFD and 92 volunteers without IFD underwent detection, and the receiver operating characteristic curve of the GFαSub252-668 double-sandwich method was described. The sensitivity and specificity of the GFαSub252-668 double-sandwich method were 91.67 and 82.61%, respectively, and there was good correlation with the G test for the serum specimens of 36 patients with pulmonary IFD (R2 = 0.7592). In conclusion, our study suggests that the GFαSub252-668 double-sandwich method was satisfactory at detecting IFD cases. This method can be promoted and further developed as a novel method for diagnosing IFD.

Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) are mostly unilateral and rarely spread to the bilateral cortex and meninges. We describe a case of MOG-immunoglobulin G (IgG) associated disorder (MOGAD) in a 39-year-old male with bilateral meningo-cortical involvement. The patient was hospitalized for epilepsy, fever, and headache. The initial MRI revealed abnormalities in the sulci of the bilateral frontal, temporal, and parietal lobes. He was considered to have infectious encephalitis and given empiric antibiotic and antiviral therapy, which were ineffective. His condition rapidly improved after the patient was switched to high-dose immunoglobulin therapy. No tests supported the presence of central nervous system (CNS) infections or autoimmune encephalitis. The second and third MRI scans showed reduced but still clearly observable meningo-cortical lesions. The patient was discharged without a definite diagnosis, but reported severe left vision impairment 25 days later. A fourth MRI showed signs typical of demyelinating CNS disease in addition to the original meningo-cortical lesions. The patient's symptoms were initially relieved by low-dose corticosteroid therapy, but they eventually returned, and he was re-admitted. The original lesions were diminished on the fifth MRI scan, but new lesions had developed in the deep white matter. A positive cell-based assay for MOG-IgG in serum confirmed MOGAD. The patient received high-dose corticosteroid treatment followed by an oral methylprednisolone taper, and his visual acuity gradually improved. The sixth and final MRI showed substantial decreases in the original lesions without new lesion formation. This unique case presents the complete diagnosis and treatment process for MOGAD with bilateral meningo-cortical involvement and may provide a reference for prompt diagnosis.

Jute fibers are commonly used as reinforcement in composite materials manufacture due to its excellent mechanical properties. In this study, alkali (NaOH) and silane coupling agent KH570 treatment were conducted on component jute nonwovens to improve the bonding strength of jute/PLA composite interface. The jute/PLA composites were prepared from treated jute nonwovens and PLA films by molding method. The results show that alkali treatment can significantly improve the tensile, flexural and dynamic thermomechanical properties of jute/PLA composites. The composites treated with 1% NaOH exhibits the maximum tensile strength while the composites treated with 5% NaOH presents the maximum flexural strength and the minimum loss in the dynamic thermo-mechanical process. Moreover, the tensile and flexural strength of the composite treated with the combination of 5% NaOH-5% KH570 is significantly stronger than that when they act alone. This research can provide an optimal treatment strategy for the jute/PLA degradable composites with higher mechanical and thermos-mechanical tolerance. [ABSTRACT FROM AUTHOR]

Abstract. Background:. It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival. Methods:. Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis. Results:. The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34–47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P

Abstract Purpose We propose a collaborative and secure transmission scheme in order to safely and efficiently transmit medical data and provide telemedicine services, lighten the load on wireless access networks, and improve the quality of medical treatment such as surgery. Methods First, the transmission technology based on opportunistic networks is used to upload patient physiological data and share medical information. Second, we propose a trusted transfer scheme based on the circle of friends, which is constructed with historical encounters and social features of nodes. This scheme takes the forwarding policy of each packet by close friends to effectively prevent the participation of strangers, and avoid privacy issues and deal with selfish behaviors. At the same time, the structure of friend circle is beneficial to the improvement of medical data transmission. Third, we present a lossless compression scheme with less computation and higher compression ratio to reduce the amount of medical data and improve the performance of the transmission. Results The experimental results show that the proposed scheme is effective and has good transmission performance while ensuring the safety and reliability of media data. Conclusion The mobile healthcare faces some challenges such as the vastness of medical data and sensitivity of patient information. Using opportunistic networks to transmit medical data in mobile healthcare is a good solution, which can effectively divert and offload the data traffic of mobile Internet. The structure of friend circles and the technology of data compression are beneficial to safely and efficiently transmit the patient’s physiological parameters and medical health information.

A more realistic alcoholism model on scale-free networks with demographic and nonlinear infectivity is introduced in this paper. The basic reproduction number $R_{0} $ is derived from the next-generation method. Global stability of the alcohol-free equilibrium is obtained. The persistence of our model is also derived. Furthermore, the SAITS model with nonlinear infectivity is also investigated. Stability of all the equilibria and persistence are also obtained. Some numerical simulations are also presented to verify and extend our theoretical results.

Within the framework of Dyson–Schwinger equations of QCD, we study the finite volume effects on the chiral phase transition, especially the influence on the position of the possible pseudo-critical end point (pCEP). The results show that in the chiral limit case (the current quark mass m=0), the absolute value of quark condensate decreases for smaller volumes, and more interestingly, so does the pseudo-critical temperature Tc(μ=0), which is in agreement with the Polyakov Nambu–Jona-Lasinio model result and opposite to the Polyakov linear sigma model prediction. These conclusions hold for m>0 case in our calculations. Moreover, the results of pCEP as a function of different volumes show that T of pCEP also decreases for smaller volumes, but μ of pCEP will increase, which are qualitatively more close to Polyakov linear sigma model results. For our model setup, results for systems with a size larger than (5 fm)3 closely approximate those from infinite volume, but if the volume is smaller, the corrections are non-negligible, even significantly affect signatures of the results from an infinite system. There also exists some possibility that, if the system size is too small, the whole phase transition would be crossover, which means no pCEP exists at all. It is no doubt that, finite volume effects deserve further researches.

Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P < 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P < 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P < 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.

After reviewing the diagnosis and treatment process of a patient with active cancer who experienced wake-up stroke, we have summarized the clinical manifestations, laboratory examination results, imaging features, pathological results, and treatment in this report. Patients with active cancer who experience wake-up stroke often have mild neurological deficits at the time of onset. For the patient in this study, laboratory test results were mainly characterized by abnormal coagulation function and elevated tumor markers. The brain magnetic resonance imaging (MRI) images were characterized by involvement of both the arterial and venous systems. Thrombolytic therapy during the window period can improve the symptoms of neurological deficits. Overall, anticoagulation therapy was safe and effective in our patient.

Background: Long non-coding RNA FGD5 antisense RNA 1 (FGD5-AS1), identified to be a carcinogenic lncRNA, exhibits a regulatory role in some malignancies including non-small cell lung cancer (NSCLC). The aim of the present research is to decipher the function and underlying mechanism of FGD5-AS1 in progression of NSCLC. Methods: Expression of FGD5-AS1, miR-493-5p and DEAD-box protein 5 (DDX5) in NSCLC tissues and cells was quantified utilizing qRT-PCR. Cell proliferation was assessed by CCK-8 method. Scratch healing test and Transwell assay were used for assaying cell migration and invasion. Expressions of DDX5 and epithelial-mesenchymal transition (EMT)-related proteins were examined by Western blot. Additionally, targeting relationships between FGD5-AS1 and miR-493-5p, miR-493-5p and DDX5 were verified by dual-luciferase reporter gene assay. Results: Expression of FGD5-AS1 in NSCLC tissues and cell lines was up-regulated. Expression of FGD5-AS1 was in association with enlarged tumor size and lymph node metastasis of the patients. Knockdown of FGD5-AS1 led to the inhibition of proliferation, migration, invasion and EMT of NSCLC cells. FGD5-AS1 directly targeted miR-493-5p, while DDX5 was the target of miR-493-5p in NSCLC cells. Additionally, FGD5-AS1 could positively regulate the expression of DDX5 via suppressing miR-493-5p. Conclusion: FGD5-AS1 facilitates the proliferation, migration, invasion and EMT of NSCLC cells by sponging miR-493-5p and up-regulating DDX5.

Objective This study was designed to analyze the relationship between tumor metastasis and acute ischemic stroke (AIS) in Chinese cancer patients. Methods This retrospective study included 119 cancer patients with AIS and 152 cancer patients without AIS. Basic information was collected and tumor metastasis status was determined for all patients. Results The whole cohort had a median age of 59 (49–69) years with 150 men (55.4%). There were 98 patients (36.2%) with tumor metastasis. Patients with AIS had significantly more males, tumor metastasis, lung cancer, hypertension, diabetes mellitus, higher age, D-dimer, international normalized ratio, prothrombin time, prothrombin activity, and thrombin time, while they had significantly lower levels of hemoglobin, red blood cells, and hematocrit. In multivariate logistic regression analysis, AIS was significantly and positively associated with age, tumor metastasis, D-dimer, and thrombin time. In multivariate Cox regression analysis, tumor metastasis, AIS, D-dimer, thrombin time, and fibrinogen were significantly and positively associated with worse prognosis. Conclusions This study demonstrates that tumor metastasis was positively and independently associated with AIS in Chinese cancer patients, suggesting that tumor metastasis has a significant relationship with the development of AIS. Additionally, tumor metastasis and AIS had negative independent effects on the prognosis of patients.

The height of the fractured zone caused by coal mining is extremely significant for safely mining under water, water conservation, and gas treatment. At present, the common prediction methods of overburden fractured zone height are only applicable to thin and medium-thick coal seams, not suitable for thick and extra-thick coal seams. In order to determine the overburden fractured zone distribution characteristics of extra-thick seam mining, failure process analysis method of overlying strata was proposed based on key strata theory. This method was applied to 15 m coal seam of Tongxin coal mine, and fractured zone height was determined to be 174 m for 8100 panel. EH4 electromagnetic image system and borehole televiewer survey were also conducted to verify the theory results. The distribution of the electrical conductivity showed that the failure height was 150–170 m. Observation through the borehole televiewer showed that the fractured zone height was 171 m. The results of the two field test methods showed that the fractured zone height was 150–171 m, and it was consistent with the theory calculation results. Therefore, this failure process analysis method of overlying strata can be safely used for other coal mines.

Aim. To explore the expression of long noncoding RNA (LncRNA) LUCAT1 in adult patients with Crohn’s disease (CD) and evaluate the relationship between LncRNA LUCAT1 and the disease activity in Chinese patients with CD. Methods. Patients with CD and healthy participants (≥18 years old) were enrolled in this study between January 2018 and December 2019. The expression of LncRNA LUCAT1 in plasma samples was evaluated by quantitative reverse transcription-polymerase chain reaction. Basic characteristics of patients with CD were collected, including gender, age, clinical stage, disease behavior, disease location, C-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn’s disease activity index (CDAI) score, and simplified Crohn’s disease endoscopic score (SES-CD). Results. In total, 168 patients with CD and 65 healthy participants (≥18 years old) were enrolled in this study. Among them, ninety patients with clinically active CD, seventy-eight patients with CD in clinical remission, forty-eight patients with endoscopically active CD, thirty patients with endoscopically inactive CD, and sixty-five healthy participants. LncRNA LUCAT1 was increased in plasma of patients with CD compared with the control group. The plasma LncRNA LUCAT1 level of patients with CD both in the clinical and endoscopic active phase was higher than that of both the clinical and endoscopic remission phase. The plasma level of LncRNA LUCAT1 in patients with CD was positively correlated with ESR, CRP, FC, CDAI, and SES-CD. There was no significant correlation between the level of LUCAT1 and platelets. The plasma LncRNA LUCAT1 level in patients with CD had significant differences between severe active patients and mild/moderate active patients. Conclusion. The plasma LncRNA LUCAT1 is positively associated with the disease activity in patients with CD, and it may act as a noninvasive biomarker to identify the degree of disease activity.

A fast and sensitive carcinoembryonic antigen (CEA) aptasensor with multiple detection modes was developed. It is based on hollow gold nanoparticles (HGNPs) and horse radish peroxidase (HRP) as both labels and signal amplification elements. In fabrication, capture DNA (cpDNA) was modified on magnetic beads, and reporter DNA (rpDNA) and HRP were co-modified on HGNPs. A combination DNA, containing a DNA aptamer (GAC-P) segment, hybridized with cpDNA and rpDNA, forming a satellite-structured biosensor. In response to CEA, the aptamer switches its structure, releasing rpDNA/HGNPs/HRP under magnetic separation. The surface plasmon resonance of HGNPs and the HRP enzyme activity of the supernatant were observed/detected with naked eyes, UV–vis spectroscopy, and electrochemistry techniques. The assay time is as short as ~45 min. CEA levels can be differentiated with naked eyes. The absorbance at 677 nm is linearly proportional to CEA concentration from 10 to 250 ng mL−1, with a limit of detection (LOD) of 8.6 ng mL−1. In contrast, the differential pulse voltammetry (DPV) peak current at -0.057 V is linearly correlated with CEA concentration in the range of 2−250 ng mL−1, with an LOD of 0.78 ng mL−1. The LOD values are lower than cancer patient threshold levels. The aptasensor exhibits negligible responses to interfering proteins. In addition, it displays good reproducibility, stability, accuracy and easiness of usage. The recovery rate for CEA spiked human serum samples are 100±5%. The developed assay strategy should provide a general platform for detecting other interested biomarkers.

Background: Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. Mesencephalic astrocyte-derived neurotrophic factor (MANF) can inhibit ERS. This study aimed at investigating the effect of MANF on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation. Methods: Experimental grouping: blank control group, blank control + MANF group, lentivirus group, lentivirus + MANF group, S63del MPZ group, S63del MPZ + MANF group. CCK8 and Annexin-FITC/PI were used to detect cell proliferation and apoptosis. JC-1 was used to detect ΔΨm. MANF, GRP78 and CHOP mRNA and protein were detected by using RT-qPCR, western blotting and immunofluorescence. ER-Tracker and mito-tracker were used to observe the morphology of endoplasmic reticulum (ER) and mitochondria. Results: Cell proliferation decreased (p < 0.001) and apoptosis increased (p < 0.001) in S63del MPZ group; cell proliferation increased (p = 0.005) and apoptosis decreased (p < 0.001) in S63del MPZ + MANF group. ΔΨm decreased (p < 0.001), MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 increased (p < 0.001) and Bcl2 decreased (p < 0.001) in S63del MPZ group. MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 decreased (p < 0.001) and Bcl2 increased (p < 0.001) in S63del MPZ group. Conclusions: ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANF exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation.

Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI.

Objectives: This study compared neurofilament light chain (NFL) levels in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with levels in patients with other neurological diseases and healthy controls and assessed correlations between NFL levels and clinical indicators of sALS.Methods: We used enzyme-linked immunosorbent assays to determine the NFL levels in the CSF of 45 patients with sALS, 21 patients with other central nervous system diseases (OCNSDs), 18 with immune-mediated peripheral neuropathy (IMPN), 14 with non-immune-mediated peripheral neuropathy (NIMPN), and 19 healthy controls (HCs).Results: The median NFL levels in the CSF of the sALS, OCNSD, IMPN, NIMPN, and HC groups were 6510, 5372, 4320, 1477, and 756 pg/mL, respectively. The CSF NFL levels did not differ significantly among the sALS, IMPN, and OCNSD groups, but were significantly higher than those of the NIMPN and HC groups. The NFL CSF levels were significantly higher in the NIMPN group than the HCs. There was a negative correlation between the NFL level and ALS function score (ALSFRS-R), and a positive correlation with the disease progression rate in patients with sALS.Conclusion: CSF NFL may not be sufficient to distinguish ALS from other central nervous system diseases or peripheral neuropathy, but it predicts ALS severity and progression.

Background: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease characterized by muscle weakness and multisystemic impairments, which significantly impact the quality of life. There is currently an increasing consensus on the necessity of a multidisciplinary assessment in patients with DM1, to improve the management of the disease.Methods: To analyze the prevalence and pairwise relationships between various organs involved, we performed a retrospective study by reviewing demographic and clinical information of DM1 patients including age, disease duration, clinical history, muscular impairment rating scale score (MIRS), results of blood biochemistry, electrocardiogram, echocardiography, and ophthalmologic examination.Results: Ninety three DM1 patients (60 males and 33 females), aged 34.7 ± 12.6 (mean ± standard deviation) years were recruited. Of which, two congenital cases were of maternal and paternal inheritance, respectively. In the other 91 patients, cataract was found in 44.1% of patients, followed by hypogonadism (40.8%), frontal balding (40.7%), and cardiac abnormalities (34.5%). Thyroid dysfunction and insulin insensitivity were relatively uncommon. Age (p < 0.001) is independently correlated with cataract, and MIRS correlates positively with cardiac abnormalities (p = 0.005) and frontal balding (p = 0.015). Male patients more frequently had frontal balding (Risk ratio, 3.98; 95% confidence interval, 1.493–10.611) compared with female patients. Male patients with cataract presented more frequent cardiac abnormalities (Risk ratio, 4.40; 95% confidence interval, 1.055–18.358) compared with non-cataract male patients. Hypogonadism in male patients was characterized as decreased testosterone level, accompanied by elevated levels of luteinizing hormone and follicle-stimulating hormone.Conclusions: In Chinese patients with DM1, we conclude that (1) cataract, hypogonadism, frontal balding and cardiac abnormalities are frequently observed; (2) age is an independent indicator to cataract and MIRS is the only predictor for cardiac abnormalities and frontal balding; (3) a positive correlation between ophthalmologic and cardiac impairments in male patients is found; (4) endocrine abnormalities show diverse manifestations and hormone tests are recommended; (5) particular attention should be given to patients with older age and higher MIRS score.

Objectives Interleukin-37 (IL-37) has been identified as a potent inhibitor of the immune response. This study aimed to examine IL-37 expression in patients with chronic active hepatitis B (CAHB), and explore its possible regulatory role during inflammation. Methods Peripheral blood mononuclear cells (PBMCs) were collected from control (n = 20) and CAHB patients (n = 30) before and after treatment with entecavir (EVT) for 24 weeks. The PBMCs were cultured with lipopolysaccharide and IL-37 expression was determined by real-time polymerase chain reaction and flow cytometry. The mRNA and protein concentrations of IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in PBMCs were also measured. Results Levels of IL-37, IL-1β, IL-6, and TNF-α were significantly increased in the supernatant of PBMCs from patients with CAHB. IL-37 significantly reduced the expression of IL-1β, IL-6, and TNF-α. EVT resulted in regression of intraocular inflammation in patients with CAHB, associated with decreased production of IL-37. Conclusion These results suggest that increased expression of IL-37 was associated with the suppression of the inflammatory response in patients with CAHB. Furthermore, EVT treatment of CAHB was also correlated with downregulation of IL-37, indicating that EVT may partially alleviate the immune response by modulating IL-37 production.

AimOur previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can confer hepatic protection by reducing endoplasmic reticulum stress (ERS) in high-fat-high-fructose induced metabolic syndrome (MS) rats. It is known that there is a functional coupling between autophagy and ERS. This study aimed to investigate the effect of CIHH on autophagy function and adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPKα-mTOR) signaling pathway in hepatic tissue of MS rats.Main Methods6-week old male Sprague-Dawley rats were randomly divided into: control (CON), CIHH (treated with hypobaric hypoxia simulating 5000-m altitude for 28 days, 6 h daily), MS (induced by 16-week high fat diet and 10% fructose water feeding), and MS + CIHH groups (exposed to CIHH after 16-week MS model). Food and water intakes, body weight, Lee’s index, fat coefficient, systolic arterial pressure, blood biochemicals, and histopathology of liver were measured, the expression of phosphorylated (p)-AMPK, p-mTOR, autophagy-related and ERS-related proteins were assayed in hepatic tissue.Key FindingsThe MS rats displayed obesity, hypertension, polydipsia, glucose and lipids metabolism disorders, increased inflammatory cytokine, hepatic tissue morphological and functional damage, and the up-regulated expressions of ERS-related, autophagy-related proteins and p-mTOR, and the down-regulated expression of p-AMPKα. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats.SignificanceIn conclusion CIHH confers hepatic protection through activating AMPK-mTOR signaling pathway and the autophagy function, thus inhibiting ERS in hepatic tissue.

“Social mindfulness” refers to being thoughtful of others and considering their needs before making decisions, and can be characterized by low-cost and subtle gestures. The present study compared the behavioral and neural responses triggered by observing others’ socially mindful/unmindful choices and how these responses were modulated by the social status of the agency. At the behavioral level, observing socially mindful choices made observers feel better, rate the actors as more likable, and behave more cooperatively than did observing socially unmindful choices. Analysis of event-related potentials in the brain revealed that compared with socially unmindful choices, mindful choices elicited more negative feedback-related negativity (FRN). Notably, while this effect of social mindfulness was only significant when the actor’s social status was medium and high, it was undetectable when the actor’s social status was low. These results demonstrate that the social mindfulness of others can be rapidly detected and processed, as reflected by FRN, even though it does not seem to receive further, more elaborate evaluation. These findings indicated that low-cost cooperative behaviors such as social mindfulness can also be detected and appreciated by our brain, which may result in better mood and more cooperative behaviors in the perceivers. Besides, the perception of social mindfulness is sensitive to important social information, such as social status.

Abstract Solutions and their evolutions of the quark gap equation are studied within the Nambu–Jona–Lasinio model, which is a basic issue for studying the QCD phase structure and locating the possible critical end point. It is shown that in the chiral limit case of the vacuum, chiral symmetry will hold if the coupling strength G is small, then the system only has the Wigner solution at $$M\,=\,0$$ M=0 . If increasing G, two symmetric minima will appear as the positive and “negative” Nambu solutions, however, the solution $$M\,=\,0$$ M=0 now corresponds to a maximum instead of a minimum of the thermodynamical potential, so is not a physically stable state anymore (we call it “pseudo-Wigner solution”). Besides, it is shown that as the current quark mass m increases, the pseudo-Wigner solution will become negative, and disappear together with the negative Nambu solution if m is large enough. Similar things happen if we increase the temperature or quark chemical potential $$\mu $$ μ . Some interesting phenomenon is, from some $$\mu $$ μ a second local minimum will show up. As $$\mu $$ μ increases gradually, it will be stabler than the Nambu solution, survives even the Nambu solution disappears, and approaches m, which are just the features of the Wigner solution we expect.

Gesture recognition has remained a challenging problem in the fields of human robot interaction. With the development of depth sensors such as Kinect, different modalities become available for gesture recognition while its advantages have not been fully exploited. One of the critical issues for multi-modal gesture recognition is how to fuse features from different modalities. In this article, we present a unified framework for multi-modal gesture recognition based on dynamic time warping. The 3D implicit shape model is applied to characterize the space-time structure of the local features extracted from different modalities. And then, all votes from the local features are incorporated into a common probability space which is then used for building the distance matrix. Meanwhile, an upper-bounding method UB_Pro is proposed to speed up dynamic time warping. The proposed approach is evaluated on the challenging ChaLearn Isolated Gesture Dataset, showing comparable performance in comparison to the state-of-the-art approaches for multi-modal gesture recognition problem.

To establish the movement relationship for the roof breaking under shallow mining conditions, the mechanical model of the roof rock beam was built, then the structure instability process of the roof rock beam was analyzed. The changing criterion of the vertical displacement was established and the relationship between the deflection and the rotary motion of roof block was determined. Regarding a mining face in Shangwan Mine, the responsing laws of the deflection and horizontal thrust of the roof rock beam were obtained through FLAC3D numerical analysis. The results show that the structure instability of the cracked roof rock beam depends on the interaction between the vertical load and the horizontal thrust. For the roof rock beam, when the vertical load keeps constant, the horizontal thrust fluctuating rises with increasing deflection. The horizontal thrust increases constantly with the deeper buried depth and the smaller span. Keywords: Shallow mining, Working face, Roof rock beam, Structure stability, Horizontal thrust

Background: Nowadays, it is widely known that decremental responses in low-frequency repetitive nerve stimulation (LF-RNS) are frequently observed in patients with amyotrophic lateral sclerosis (ALS). The pathological mechanism of this phenomenon remains unknown. This study aimed to illuminate the features of RNS in Chinese patients with ALS. Methods: Clinical and electrophysiological data of 146 probable and definite ALS patients who underwent RNS were retrospectively enrolled and analyzed. LF-RNS (3 Hz) was performed in trapezius, deltoid, abductor digiti minimi (ADM), quadriceps femoris, and tibialis anterior. High-frequency RNS (HF-RNS, 10 Hz) was performed only in ADM. The two-sample t-test and Chi-squared test were used for statistical analysis. Results: Decremental responses to LF-RNS (≥10%) in at least one muscle were detected in 83 (56.8%) of the cases and were most commonly seen in trapezius and deltoid. The incidence of decremental response was higher in patients with upper limb onset. Incremental responses to HF-RNS (≥60%) in ADM were observed in 6 (5.6%) of the cases. In 106 muscles with decremental response, 62 (57.4%) muscles had a continuous decremental pattern, more than a U-shape pattern (37 cases, 34.3%). Nineteen cases showed definite decrements in LF-RNS tests in trapezius, while no abnormalities were found in the electromyography and neurological examination of the sternocleidomastoid muscle, supplied by the accessory nerve as well. Conclusions: Decremental responses in the RNS are commonly observed in ALS patients. The findings regarding the trapezius indicated that some ALS onsets could be initiated by a “dying back” process, with destruction of neuromuscular junctions (NMJs) before motor neurons. Incremental responses in the ADM implied damage of the NMJs involved both the post and presynaptic membranes.

Materials with designed gradient nanograins exhibit unprecedented mechanical properties, such as superior strength and ductility. In this study, a heterostructured 304 stainless steel with solely gradient dislocation structure (GDS) in micron-sized grains produced by cyclic-torsion processing was demonstrated to exhibit a substantially improved yield strength with slightly reduced uniform elongation, compared with its coarse grained counterparts. Microstructural observations reveal that multiple deformation mechanisms, associated with the formation of dense dislocation patterns, deformation twins and martensitic phase, are activated upon straining and contribute to the delocalized plastic deformation and the superior mechanical performance of the GDS 304 stainless steel.

Abstract Background The differentiation and maturation trajectories of fetal liver stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution, and a priori knowledge of limited biomarkers could restrict trajectory tracking. Results We employed marker-free single-cell RNA-Seq to characterize comprehensive transcriptional profiles of 507 cells randomly selected from seven stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver development, and also 52 Epcam-positive cholangiocytes from postnatal day 3.25 mouse livers. LSPCs in developing mouse livers were identified via marker-free transcriptomic profiling. Single-cell resolution dynamic developmental trajectories of LSPCs exhibited contiguous but discrete genetic control through transcription factors and signaling pathways. The gene expression profiles of cholangiocytes were more close to that of embryonic day 11.5 rather than other later staged LSPCs, cuing the fate decision stage of LSPCs. Our marker-free approach also allows systematic assessment and prediction of isolation biomarkers for LSPCs. Conclusions Our data provide not only a valuable resource but also novel insights into the fate decision and transcriptional control of self-renewal, differentiation and maturation of LSPCs.