[A review on the role of angiotensin-converting enzyme 2 in children with coronavirus disease 2019].

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world, there is an increasing number of children with such infection. Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children. The article summarizes the research advances in the role of ACE2 during SARS-CoV-2 infection, in order to help understand the pathogenic mechanism of SARS-CoV-2 and provide a reference for better development of drugs and vaccines to prevent and treat coronavirus disease 2019 in children.

Effectiveness of backward walking for people affected by stroke: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Backward walking (BW) training is increasingly used in rehabilitation for stroke, but relevant evidence remains unclear. OBJECTIVE: To determine the effect of BW training on patients with stroke. METHODS: A keyword search was conducted in PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure database for articles published until November, 2019. Two investigators screened the articles and extract data from each included study. Meta-analysis was performed to estimate the effect of BW on stroke. In addition, the quality of evidence was evaluated by GRADE (grading of recommendations, assessment, development, and evaluation; version:3.6) approach. RESULTS: A total of ten studies were included according to the inclusion and exclusion criteria in the review. All included studies described some positive influences of BW on stroke relative to the control group (forward walking or conventional treatment). Compared to control group, there is a statistically significant improvement for BW group in gait velocity (mean difference [MD] = 6.87, 95%CI: [1.40, 12.33], P = .01, I = 3%), Berg balance score (MD =3.82, 95%CI: [2.12, 5.52], P < .0001, I = 0%), and walk test (MD =0.11, 95%CI: [0.02, 0.20], P = .02, I = 36%). CONCLUSIONS: For patients with stroke, BW training, as an adjunct an adjunct to conventional treatment, can improve Berg balance score (moderate evidence), walk test performance (very low evidence), gait velocity (very low evidence). More large-scale and high-quality studies are warranted.

[Spatial autocorrelation analysis of land use and ecosystem service value in Maduo County, Qinghai Province, China at the grid scale]. / æ ¼ç½‘å°ºåº¦ä¸‹é’æµ·çŽ›å¤šåŽ¿åœŸåœ°åˆ©ç”¨åŠç”Ÿæ€ç³»ç»ŸæœåŠ¡ä»·å€¼ç©ºé—´è‡ªç›¸å ³åˆ†æž.

Research on the spatial quantitative evaluation of land use and ecosystem service value in the source region of the Yellow River is of great significance for ensuring the ecological security of the river basin. Taking Maduo County in the source region of the Yellow River as an example, based on a 3 km × 3 km grid unit, the spatial autocorrelation method was applied to construct an evaluation model of ecosystem service value. The spatial autocorrelation pattern characteristics of Maduo County in 2015 was quantitatively evaluated, and the spatial information of ecosystem service value was visually expressed. The results showed that, at the examined grid scale, the area of grasslands with different coverages was large, and water grid area accounted for 42.9% of the total grids and was mainly distributed in the northwest of Maduo County. The construction land showed a "line-like" distribution from northeast to southwest, while the unutilized land was more distributed in southwest and less in northeast. In space, different land use type grids interacted with each other, with positive correlation and cluster distribution. The values of global Moran I and local Moran I of water area was the largest, with strongest spatial aggregation and high local connectivity. The global Moran I and local Moran I values of the construction land were 0.293 and 0.127, respectively, with the weakest spatial autocorrelation and clustering characteristics in a small range. In 2015, ecosystem service value (ESV) of Maduo County was 93.887 billion yuan, the mean ESV across all the grids was 3.20×107 yuan, with a maximum of 19.96×107 yuan. The water distribution grid had high ESV. On the whole, the ESV distribution pattern in Maduo County had a significant spatial positive correlation, with clustered ESV grids. The ESV grids of different land use types generally showed high-high cluster and low-low cluster, with the spatial pattern of high-low cluster and low-high cluster being sporadic. We proposed several possible strategies of land space planning and use control. First, the water and unused land should adopt a "centralized continuum" protection mode that emphasize the value of ecological spillovers. Second, grasslands with different coverage levels should adopt a "group-type" eco-governance model of primary and secondary division and zoning management. Third, construction land should adopt a small-scale intensive development and utilization model in a "corridor " distribution pattern.

Effect of Early and Intensive Rehabilitation after Ischemic Stroke on Functional Recovery of the Lower Limbs: A Pilot, Randomized Trial.

OBJECTIVE: We aimed to develop an early and intense lower extremity training technique using a recumbent cycle ergometer system in patients with acute ischemic stroke. METHODS: This was a pilot, prospective, randomized, controlled study with 2 parallel groups followed for 3 months with blinded assessment of outcomes. Thirty-one eligible patients were randomized to experimental and control groups. To strengthen the motion of the lower extremities within 48 hours after stroke, the control and experimental groups received conventional treatment and additional interventions under a therapist's guidance combined with conventional treatment, respectively. The primary outcome measure was the change in lower extremity motor control from admission to 4 weeks, assessed by the Fugl-Meyer Assessment. Secondary outcomes were the number of days to walking 50 m and the change in the Berg Balance Scale score and Barthel index. The modified Rankin Score was used to assess the overall function and prognosis at 3 months. RESULTS: Fugl-Meyer Assessment and Berg Balance Scale scores and Barthel index increased over time in the experimental group, as did the Berg Balance Scale score and Barthel index in the control group (P < .001). However, Fugl-Meyer Assessment scores in the control group were similar over time (F = 2.303, P = 1.119). Fugl-Meyer Assessment scores in the experimental group were higher than those in the control group after 2 and 4 weeks (P = .084 and .037, respectively). Compared with the control group at 2 weeks or at discharge, the percentage of patients who returned to unassisted walking in the experimental group showed an increasing trend (56.3% versus 26.67%, P = .095), but there was no significant difference between the 2 groups after 3 months (P = .598). The modified Rankin Score at 3 months showed no significant difference between the 2 groups (P > .05). CONCLUSIONS: Our early and intense lower extremity training technique involving a leg cycle ergometer system contributes to the recovery of lower extremity function in patients with acute ischemic stroke. This finding will provide a basis for future investigations on the applicability of the intervention in early lower extremity and walking rehabilitation among individuals with neurological disorder.

EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages.

In this study, we tested the potential role of astragaloside IV (AS-IV) against oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted significant neuroprotective effects against OGD/R by reducing reactive oxygen species (ROS) accumulation, thereby attenuating oxidative stress and neuronal cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40 phosphorylation, and its nuclear localization, as well as transcription of antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown of Nrf2 through lentiviral shRNAs prevented AS-IV-induced ARE genes transcription, and abolished its anti-oxidant and neuroprotective activities. Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR) in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS-IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages through activating of EGFR-Nrf2 signaling.

Slip effects on mixed convective peristaltic transport of copper-water nanofluid in an inclined channel.

Peristaltic transport of copper-water nanofluid in an inclined channel is reported in the presence of mixed convection. Both velocity and thermal slip conditions are considered. Mathematical modelling has been carried out using the long wavelength and low Reynolds number approximations. Resulting coupled system of equations is solved numerically. Quantities of interest are analyzed through graphs. Numerical values of heat transfer rate at the wall for different parameters are obtained and examined. Results showed that addition of copper nanoparticles reduces the pressure gradient, axial velocity at the center of channel, trapping and temperature. Velocity slip parameter has a decreasing effect on the velocity near the center of channel. Temperature of nanofluid increases with increase in the Grashoff number and channel inclination angle. It is further concluded that the heat transfer rate at the wall increases considerably in the presence of copper nanoparticles.

SOX2 overexpression correlates with poor prognosis in laryngeal squamous cell carcinoma.

OBJECTIVE: The aim of present study was to investigate the expression of SOX2, a key transcription factor, in LSCC and to assess its prognostic significance. METHODS: SOX2 expression of 161 LSCC tissues was detected by immunohistochemistry using a tissue microarray and statistically analyzed for its correlation with clinicopathological charateristics and patient outcome. In addition, SOX2 expression was also observed in 20 self-paired fresh LSCC tissues by western blot. RESULTS: SOX2 was overexpressed in LSCC tissues as compared to the corresponding adjacent normal tissues. SOX2 expression was significantly associated with tumour T classification (p<0.001), clinical stage (p<0.001), lymph node metastasis (p=0.007) and recurrence (p=0.001). Univariate analysis revealed that patients with high SOX2 expression were significantly related to overall survival (p<0.001). Multivariate survival analysis further demonstrated that SOX2 expression was an independent prognostic factor for LSCC patients. CONCLUSION: SOX2 may contribute to the malignant progression of laryngeal squamous cell carcinoma (LSCC), and present as a useful prognostic marker and a potential therapeutic target for LSCC patients.

Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats.

Dysfunction of adenosinergic systems has been implicated in the development of multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in animals. Caffeine, a non-selective antagonist of adenosine receptors, has been shown to provide protection against myelin oligodendroglia glycoprotein (MOG)-induced EAE in mice. In this study, we showed that chronic caffeine similarly imparts neuroprotection against EAE induced in rats by guinea pig spinal cord homogenates (GPSCH). GPSCH-induced EAE is characterized by extensive tissue inflammation with a typical chronic disease course. We showed that caffeine decreases the incidence of EAE and attenuates EAE pathology at behavioral, histological (inflammatory cell infiltration and demyelination) and neurochemical (expression of inflammatory cytokines) levels. The attenuation of GPSCH-induced pathology by chronic caffeine treatment was observed at doses of 10 and 30 mg/kg and during both peak and recovery phases of EAE. Furthermore, it was showed that chronic treatment with caffeine up-regulated A1 receptor and TGF-beta mRNAs and suppressed interferon-gamma mRNA in EAE rats. Together with previous reports, our data demonstrates that chronic treatment with caffeine exerts a neuroprotective effect against EAE, possibly through an A(1) receptor-mediated shift from Th1 to Th2 cell function, and provides a neurobiological basis for epidemiological investigation into the possible relationship between caffeine consumption and development of multiple sclerosis in humans.

Idazoxan attenuates spinal cord injury by enhanced astrocytic activation and reduced microglial activation in rat experimental autoimmune encephalomyelitis.

Idazoxan, an imidazoline 2 receptor (I(2)R) ligand, has been shown to protect against brain injury in several animal models of neurological disorders. In the present study we investigated the effect of idazoxan on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced by immunizing Wistar rats with guinea pig spinal cord homogenates emulsified in CFA, followed by daily treatment of idazoxan (0, 0.5 mg/kg, 1.5 mg/kg, 4.5 mg/kg, i.p, bid) for 10 days. The results showed that the treatment of idazoxan (1.5 mg/kg and 4.5 mg/kg) significantly decreased the incidence and alleviated inflammatory cell infiltration and demyelination in spinal cords and cerebral cortex. Furthermore, the protective effect of idazoxan on EAE was associated with the enhanced astrocytic activation and attenuated microglial activation and with the subsequent down-regulated expression of proinflammatory cytokines IL-12p40 and IFN-gamma and up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-beta(1). Thus, the daily treatment of the I(2)R ligand idazoxan for 10 days attenuates EAE pathology by differential modulation of astrocytic and microglial activations, raising a possibility that the I(2)R ligand may be a novel strategy for treating EAE.

[Changes of alkaline phosphatase sugar chains in hepatocellular carcinoma tissue].

OBJECTIVE: To investigate the changes of sugar chain structures of alkaline phosphatase (ALP) in hepatoma tissue and its relation to the invasiveness of hepatocellular carcinoma (HCC). METHODS: The binding ratios of ALP from 9 normal liver tissues, 16 hepatoma tissues and 16 noncancerous tissues surrounding hepatoma were analysed by affinity chromatography on various lectin columns including leukoagglutinating phytohemagglutinin (L-PHA), lentil lectin (LCA), Datura stramonium agglutinin (DSA), erythroagglutinating phytohemagglutinin (E-PHA) and Sambucus nigra bark agglutinin (SNA). RESULTS: The binding ratios of ALP on L-PHA (22.94%+/-5.30%), DSA (55.97%+/-13.72%), LCA (38.16%+/-8.87%), E-PHA (11.56%+/-4.81%) and SNA (69.80%+/-13.71%) in HCC tissues were significantly increased (P<0.01) compared with that in normal liver tissues (L-PHA 5.89%+/-2.75%, DSA 36.20%+/-11.58%, LCA 17.90%+/-6.71%, E-PHA 5.38%+/-2.20%, SNA 57.32%+/-11.27%), respectively. t values between the two groups were 8.94, 3.64, 5.94, 3.62 and 2.32, respectively. L-PHA-binding ratio (25.84%+/-4.67%) of ALP in HCC with invasiveness was significantly higher than that (18.10%+/-3.64%) without invasiveness (t=3.71, P<0.01). CONCLUSION: The changes of ALP sugar chain structures occur in HCC tissue. b1-6 branching sugar chain structure of ALP is related to the invasiveness of HCC.