Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ...ventromedial medulla (RVM) has been the most studied, whereas little is known about direct corticospinal modulation. Here, we found that stimulation in the anterior cingulate cortex (ACC) potentiated spinal excitatory synaptic transmission and this modulation is independent of the RVM. Peripheral nerve injury enhanced the spinal synaptic transmission and occluded the ACC-spinal cord facilitation. Inhibition of ACC reduced the enhanced spinal synaptic transmission caused by nerve injury. Finally, using optogenetics, we showed that selective activation of ACC-spinal cord projecting neurons caused behavioral pain sensitization, while inhibiting the projection induced analgesic effects. Our results provide strong evidence that ACC stimulation facilitates spinal sensory excitatory transmission by a RVM-independent manner, and that such top-down facilitation may contribute to the process of chronic neuropathic pain.
The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI ...symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.
COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.
Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m
A methylation and changed binding capacity with ACE2.
We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad ...BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with ...schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
This panel study investigates how temperature, humidity, and their interaction affect chronic obstructive pulmonary disease (COPD) patients’ self-reported symptoms. One hundred and six COPD patients ...from Shanghai, China, were enrolled, and age, smoking status, St. George Respiratory Questionnaire (SGRQ) score, and lung function index were recorded at baseline. The participants were asked to record their indoor temperature, humidity, and symptoms on diary cards between January 2011 and June 2012. Altogether, 82 patients finished the study. There was a significant interactive effect between temperature and humidity (
p
< 0.0001) on COPD patients. When the indoor humidity was low, moderate, and high, the indoor temperature ORs were 0.969 (95% CI 0.922 to 1.017), 0.977 (0.962 to 0.999), and 0.920 (95% CI 0.908 to 0.933), respectively. Low temperature was a risk factor for COPD patients, and high humidity enhanced its risk on COPD. The indoor temperature should be kept at least on average at 18.2 °C, while the humidity should be less than 70%. This study demonstrates that temperature and humidity were associated with COPD patients’ symptoms, and high humidity would enhance the risk of COPD due to low temperature.
Median filtering, being an order statistic filtering, has been widely used in image denoising and recently also in image anti-forensics and anti-steganalysis. In the past few years, several methods ...have been developed for median filtering detection. However, it is still a challenging task to detect median filtering in JPEG compressed images. In this paper, we propose a novel method to solve this challenging task. We first generate median filtered residual (MFR), average filtered residual (AFR) and Gaussian filtered residual (GFR) by calculating the differences between an original image and its filtered images. Then, we propose to use two-dimensional autoregressive (2D-AR) model to characterize MFR, AFR and GFR separately, and further combine the 2D-AR coefficients of these three residuals into a set of features. Finally, the extracted feature set is fed into a support vector machine classifier for training and detection. Extensive experiments have demonstrated that compared with existing methods, the proposed one can achieve a considerable improvement in detecting median filtering in heavily compressed images.
Background
When the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to ...radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration.
Patients and Methods
We retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed.
Results
LNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI odds ratio (OR) = 16.761
, P
< 0.001, SM1 invasion (OR = 2.159,
P
= 0.028), and SM2 invasion (OR = 3.230,
P
< 0.001) were independent risk factors for LNM. LNM occurred in undifferentiated mucosal tumors, with ulceration being 1.7% (2/116) when the lesion was smaller than 20 mm. Further stratification revealed that among lesions < 30 mm in size, undifferentiated tumors with SM1 invasion had a higher rate of LNM and a lower disease-free survival rate than differentiated tumors with SM1 invasion and tumors limited to the mucosal layer.
Conclusions
Depth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC < 30 mm in size, and additional investigation is needed to evaluate its safety.
External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host-guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by ...both H
O
-overexpressed 4T1 and H
O
-less expressed HCT116 and MCF-7 xenograft models.
The effects of evodiamine (EVO) on oral squamous cell carcinoma (OSCC) are not yet understood. Based on our earlier findings, we hypothesized that evodiamine may affect OSCC cell proliferation and ...glutamate metabolism by modulating the expression of EPRS (glutamyl‐prolyl‐tRNA synthetase 1). From GEPIA, we obtained EPRS expression data in patients with OSCC as well as survival prognosis data. An animal model using Cal27 cells in BALB/c nude mice was established. The expression of EPRS was assessed by immunofluorescence, Western blotting, and quantitative PCR. Glutamate measurements were performed to evaluate the impact of evodiamine on glutamate metabolism of Cal27 and SAS tumor cells. transient transfection techniques were used to knock down and modulate EPRS in these cells. EPRS is expressed at higher levels in OSCC than in normal tissues, and it predicts poor prognosis in patients. In a nude mouse xenograft model, evodiamine inhibited tumor growth and the expression of EPRS. Evodiamine impacted cell proliferation, glutamine metabolism, and EPRS expression on Cal27 and SAS cell lines. In EPRS knockdown cell lines, both cell proliferation and glutamine metabolism are suppressed. EPRS's overexpression partially restores evodiamine's inhibitory effects on cell proliferation and glutamine metabolism. This study provides crucial experimental evidence supporting the potential therapeutic application of evodiamine in treating OSCC. Evodiamine exhibits promising anti‐tumor effects by targeting EPRS to regulate glutamate metabolism.
Four unusual indole-terpenoids, penerpenes A–D (1–4), along with two known ones paxilline (5) and emindole SB (6), were isolated from the marine-derived fungus Penicillium sp. KFD28. The absolute ...structures of 1–4 were elucidated on the basis of spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Compounds 1 and 2 showed potent inhibitory activity toward protein tyrosine phosphatases (PTP1B and TCPTP). Plausible biosynthetic pathways of compounds 1–4 are proposed.
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