Objective:To evaluate the impact of three small compounds, namely sodium diethyldithiocarbamate (DTC), levamisole (LMS) and imiquimod (Imi), on the immunogenicity and protective efficacy of the candidate antigen PA0833 from Pseudomonas aeruginosa ( Pa) and analyze the underlying mechanisms. Methods:PA0833 was formulated with aluminum adjuvant and the above small compounds, respectively. BALB/c mice were immunized with these vaccines intramuscularly on days 0, 14 and 21. Serum samples were collected and the levels of PA0833-specific IgG were measured by ELISA. The protective efficacy of these vaccines was evaluated by assessment of survival rates, body weights, clinical scores, inflammatory factors, and histopathological changes after infecting the immunized mice with Pa PAO1 strains. Besides, the mice were injected with DTC intramuscularly for seven consecutive days to analyze the mechanism of DTC in enhancing immune response using transcriptome sequencing and flow cytometry. Results:All these small compounds were capable of effectively enhancing the immunogenicity of PA0833 formulated with aluminum adjuvant, reducing bacterial loads in lung tissues, inhibiting the secretion of TNF-α, IL-6 and IL-1β, and improving mouse survival rates upon Pa infection. DTC was more effective than the other two compounds. Transcriptome sequencing identified 121 up-regulated genes and 18 down-regulated genes in DTC-treated group as compared with PBS control group. These differentially expressed genes were significantly enriched in immune pathways, with a strong activation of the IL-17 pathway. Flow cytometry analysis demonstrated significant activation of dendritic cells and proliferation of Th17 cells in splenocytes in DTC-treated group as compared with PBS control group. Conclusions:All three small compounds are able of effectively enhance antigen immunogenicity with DTC being the most effective, indicating that DTC can be used as a novel adjuvant in vaccine development.

The accurate assessment of burn injuries is complex and difficult. The emergence of some new skin imaging techniques, such as hyperspectral imaging, unilateral magnetic resonance imaging, laser Doppler perfusion imaging, etc., has made great progress in research on burn injury assessment. With the continuous progress of imaging technology and medical imaging, medical imaging technologies such as digital radiography, computed tomography, magnetic resonance imaging, and ultrasonography, and so on, have played an important role in burn injury assessment. However, there are still relatively few research reports on burn injury imaging, which may be due to the fact that the imaging techniques and diagnostic experience used for burn injury assessment are not yet fully popular in some medical institutions, and the imaging manifestations related to burns are complex and lack of specificity. This article mainly reviews the application research progress of various imaging techniques in the assessment of burn injury in recent years, aiming to explore the application value of various imaging techniques in burn injury assessment.

Purpose To establish and validate an ultrasound-based radiomics nomogram for predicting ipsilateral axillary lymph node metastasis in stage T1 breast cancer.Materials and Methods 443 stage T1 breast cancer patients in the First Affiliated Hospital of Wannan Medical College from January 2012 to June 2021 were retrospectively collected.All patients were randomly divided into training(n=310)and validation(n=133)group.ITK-SNAP was used to delineate the tumor margins,and Pyradiomics software was used to extract features.Image omics models and Rad-scores were constructed after feature screening.Clinical model,radiomics model and combined diagnostic models were developed,with the combined model's nomogram constructed.The models'predictive values were assessed via receiver operating characteristic curves.Results Multivariate Logistic regression analysis showed that the positive axillary ultrasonography,high echo halo and abundant internal blood supply were the independent risk factors of axillary lymph node metastasis.Then the clinical model was constructed,and imaging omics model was also constructed by feature screening.The combined model,which incorporated clinical and imaging features,demonstrated superior predictive performance.In the training group,the area under the curve for the combined model was 0.822,which was significantly higher than that of the clinical model(0.765)and radiomics model(0.723)(P=0.002 1,P=0.001 8).In the validation group,the area under the curve for the combined model was 0.846,outperforming the imaging omics model(0.686,P=0.001 8)and the clinical model(0.783),though the latter difference was not statistically significant(P=0.111 3).Conclusion Ultrasound-based radiomics combined diagnostic model effectively predicts ipsilateral axillary lymph node metastasis in stage T1 breast cancer,demonstrating high clinical predictive efficiency.

BACKGROUND: Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism. METHODS: Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo . The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay. RESULTS: In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N 6 -methyladenosine (m 6 A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m 6 A site on the 3'-untransated regions (3'-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells. CONCLUSION HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
Humans ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Endothelial Cells/metabolism* ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic/genetics* ; Hypoxia ; MicroRNAs/genetics* ; RNA ; RNA, Long Noncoding/metabolism* ; RNA-Binding Proteins/metabolism* ; Scavenger Receptors, Class B/metabolism* ; Stomach Neoplasms/genetics*

新冠病毒感染疫情严重威胁着世界各国人民的生命健康。目前，对病毒感染的防治研究主要集中在抑制病毒与分子受体的结合上。AXL作为新发现的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）受体，在协助病毒感染人体呼吸系统中发挥着重要作用，是未来临床干预的潜在靶点。本研究对已发表的单细胞测序数据进行整理和分析，发现AXL在年轻人肺细胞中的表达水平明显高于老年人。人胚肺二倍体成纤维细胞（2BS）是衰老研究的公认细胞株。本文采用2BS细胞构建复制性细胞衰老模型，发现年轻细胞中AXL的蛋白水平明显高于衰老细胞，据此推测年轻人感染的风险可能更高，需要注意防护。我们发现一种羊栖菜褐藻多糖硫酸酯组分（SFW-3）可显著下调年轻2BS细胞中AXL的表达水平，表明SFW-3具有一定的抗SARS-CoV-2感染的研究价值，同时表明2BS细胞株也可作为潜在的SARS-CoV-2体外感染模型。
Humans ; SARS-CoV-2 ; Sargassum/metabolism* ; Diploidy ; Sulfates/metabolism* ; COVID-19 ; Polysaccharides/pharmacology* ; Lung

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome

Objective:To explore the abnormalities of efficiency in resting state functional brain network in patients with paranoid schizophrenia and the correlations between efficiencies and clinical symptoms.Methods:A total of 73 patients with schizophrenia (SZ group) met with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) criteria for schizophrenia and 70 healthy controls (HC group) were included .All subjects were checked by using functional magnetic resonance imaging (fMRI), and positive and negative syndrome scale(PANSS) were used to assess the symptoms.Abnormalities of global and local efficiency of brain regions in brain functional network were analyzed by graph theory.Pearson correlation was used to analyze the correlation between the abnormal global efficiency and local efficiency of brain regions of SZ group and PANSS.SPSS 20.0 software was used for dependent-sample t-test, ANOVA test and Pearson correlation analysis. Results:Compared with the HC group, SZ group showed increased global efficiency in bilateral thalamus(left: 0.26±0.06, 0.28±0.04, t=2.03, P=0.044.right: 0.26±0.06, 0.28±0.05, t=2.08, P=0.040), right orbital part of middle frontal gyrus(0.21±0.04, 0.23±0.05, t=2.25, P=0.026), cerebellar lobule Ⅸ(0.19±0.06, 0.21±0.05, t=2.56, P=0.011) and vermis Ⅲ(0.15±0.08, 0.19±0.07, t=3.27, P=0.001), while decreased global efficiency in bilateral parahippocampal gyrus(left: 0.25±0.05, 0.22±0.05, t=-3.34, P=0.001.right: 0.27±0.04, 0.23±0.05, t=-4.96, P=0.000), superior occipital gyrus(left: 0.27±0.03, 0.26±0.03, t=-2.70, P=0.008.right: 0.27±0.02, 0.26±0.03, t=-2.73, P=0.007), superior parietal gyrus(left: 0.27±0.03, 0.26±0.05, t=-2.63, P=0.010.right: 0.27±0.03, 0.25±0.05, t=-2.76, P=0.007), paracentral lobule(left: 0.28±0.03, 0.26±0.07, t=-2.47, P=0.015.right: 0.28±0.04, 0.25±0.07, t=-3.06, P=0.003), left precental gyrus(0.28±0.04, 0.27±0.04, t=-1.98, P=0.049), left cuneus(0.26±0.04, 0.25±0.04, t=-2.08, P=0.039), left lingual gyrus(0.29±0.03, 0.28±0.03, t=-2.28, P=0.024), left middle occipital gyrus(0.29±0.03, 0.28±0.03; t=-2.74, P=0.007), left middle temporal gyrus(0.28±0.03, 0.26±0.03, t=-2.73, P=0.007), temporal pole in left middle temporal gyrus(0.20±0.06, 0.18±0.06, t=-2.59, P=0.011) and right hippocampus(0.27±0.04, 0.26±0.06, t=-2.05, P=0.042).Compared with the HC group, SZ group showed increased local efficiency in bilateral caudate nucleus(left: 0.33±0.06, 0.35±0.05, t=2.54, P=0.012.right: 0.33±0.07, 0.35±0.04, t=2.77, P=0.007) and left superior occipital gyrus(0.39±0.03, 0.40±0.02, t=2.17, P=0.031), while decreased local efficiency in bilateral parahippocampal gyrus(left: 0.35±0.04, 0.32±0.07, t=-3.16, P=0.002.right: 0.34±0.04, 0.32±0.07, t=-2.91, P=0.004), left supplementary motor area(0.36±0.02, 0.35±0.05, t=-2.01, P=0.047), left inferior parietal but supramarginal and angular gyrus(0.35±0.03, 0.34±0.05, t=-2.65, P=0.009), left cerebellar crus Ⅱ(0.37±0.03, 0.36±0.04, t=-2.01, P=0.046), lobule ⅦB(0.37±0.03, 0.35±0.07, t=-1.98, P=0.049), right posterior cingulate gyrus(0.36±0.04, 0.34±0.07, t=-2.07, P=0.041), right superior parietal gyrus(0.37±0.03, 0.36±0.05, t=-2.19, P=0.031), right precuneus(0.36±0.02, 0.35±0.04, t=-2.36, P=0.020), right paracentral lobule(0.37±0.02, 0.36±0.06, t=-2.07, P=0.041) and right temporal pole in middle temporal gyrus(0.33±0.08, 0.30±0.09, t=-2.09, P=0.038).The global efficiency of bilateral paracentral lobule and left temporal pole in middle temporal gyrus in SZ group were negatively correlated with the negative scale scores( r=-0.25, -0.25, -0.26, all P<0.05).The global efficiency of right hippocampus in SZ group was positively correlated with total scores of PANSS( r=0.23, P=0.049).The global efficiency of left middle temporal gyrus in SZ group was negatively correlated with total scores of PANSS( r=-0.23, P=0.049).The local efficiency of right paracentral lobule in SZ group was negatively correlated with the positive scale scores( r=-0.24, P=0.038). Conclusion:The brain networks of patients with first-episode paranoid schizophrenia may have regional dysfunction in the transmission efficiency and fault-tolerant ability of resting state brain functional network, and the abnormalities of efficiency may be associated with the severity of psychiatric symptoms in several brain regions.

Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as the main manifestation. It often starts from one side, and the motor symptoms of different sides are different in the speed of disease development, types of non-motor symptoms and treatment response. This paper focuses on the clinical characteristics, potential mechanisms, imaging manifestations and treatment differences of lateralization of motor symptoms in PD to provide some help for the clinical diagnoses and treatments of PD.

Objective:To investigate and analyze the epidemiological and clinical characteristics of 46 patients with corona virus disease 2019 (COVID-19) in Beijing City.Methods:A retrospective study was conducted to analyze the data of 46 patients with COVID-19 in Beijing from 20th January 2020 to 8th February 2020 at the Fifth Medical Center of the PLA General Hospital in Beijing City. Twelve, 23 and 11 patients were assigned to the mild group, common group and severe group, respectively. The epidemiological history, clinical characteristics, laboratory tests and imaging inspections were analyzed. Statistical analysis used Fisher exact test. If P<0.05, post- hoc test was used for pairwise comparison, and the statistics were corrected by Bonferroni test. Results:Among the 46 patients included in this study, 27 were male and 19 were female. The age range was between 3-79 years old, and the age was (41.8±16.3) years old. The average incubation period was (4.85±3.00) days. A total of 26 cases (56.5%) were clustered patients, and 26 cases had a history of staying in Wuhan, 10 cases had contact with Wuhan personnel. Fever (39 cases, 84.8%), cough (27 cases, 58.7%), and fatigue (25 cases, 54.3%) were the main clinical symptoms for these patients. The decrease in white blood cell counts occurred in 12 patients, four had the decrease in T lymphocyte percentage, 17 had the decrease in CD4 + T lymphocyte counts, seven had the decrease in CD8 + T lymphocyte counts, 21 had the increase level of C reactive protein (45.7%), and interleukin-6 (IL-6) level increased in 32 cases (69.6%), erythrocyte sedimentation rate (ESR) increased in 23 cases (50.0%), serum ferritin level increased in 26 cases (56.5%), and blood lactic acid level increased in nine cases. There were statistically significant differences in the proportion of cases with decreased absolute value of CD8 + T lymphocytes and T lymphocytes counts among the mild, common and severe groups (all P<0.05). Comparing the proportion of cases in the three groups with elevated C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels, the differences were statistically significant (all P<0.05). The proportion of cases with elevated C reactive protein levels in severe group was higher than those in mild and common groups. The proportion of cases with elevated IL-6, ESR, and serum ferritin levels in severe and common group were higher than those in mild group. The proportion of cases with elevated blood lactic acid levels in severe group was higher than those in mild group. The differences between the above groups were statistically significant (all adjusted P<0.017). Analysis of chest X-rays results showed that 34 patients (73.9%) had inflammation in the lungs. Conclusions:The epidemiological characteristics of patients with COVID-19 in Beijing City are mainly imported cases and clustered cases. The clinical manifestations are mainly fever, fatigue and cough. C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels are higher in severe patients.

Objective:To understand the knowledge awareness and service acceptance of HIV non-occupational post-exposure prophylaxis (nPEP) men who have sex with men (MSM) among college students in three cities of China.Methods:Male college students in 10 universities of Beijing, Shenzhen and Kunming aged 18 and above who had sex with men in the last 3 months were recruited as research objects by cluster stratified sampling from March 15, 2019 to April 14, 2019.Basic information, sexual behavior characteristics, knowledge, and service acceptance of nPEP were collected through online questionnaire survey. Multivariate dichotomy and unconditioned logistic regression model was used to explore related factors about knowledge awareness and service acceptance of nPEP.Results:A total of 293 MSM were surveyed. The average age was (21.0±0.2) years old, and 91.1% (267) were undergraduates. In the last 3 months before the survey, 54.3%(159) used condom each time of sex; 4.4%(13) had intercourse with the HIV infected men, and 9.2% (27)suffered STDs in the past 6 months. The 29.4% (86) had not received HIV testing in the past year. The nPEP knowledge awareness rate was 47.8% (140). The 21.2% (62) counseled nPEP services, and 9.9% (29) received nPEP services. After multiple logistic regression analysis, compared with those who not received HIV testing in the past year, OR(95% CI) value of those who received HIV testing for more than twice in the past year to aware the nPEP knowledge was 3.15 (1.01-9.86). Compared with those who not received HIV testing in the past year, OR(95% CI) value of those who received HIV testing for more than twice in the past year to counsel the nPEP services was 5.29 (1.51-18.51). Compared with those who never used rush in the last 3 months, OR(95% CI) value of those who ever used rush in the last 3 months to receive the nPEP services was 3.86 (0.99-14.98). Compared with those who not sexed with HIV infected in the last 3 months, OR (95% CI) value of those who sexed with HIV infected in the last 3 months to receive the nPEP services was 14.30 (3.35-61.03). Conclusion:The proportions of awareness of nPEP knowledge and acceptance of nPEP services are low. MSM among college students need further health education of the nPEP knowledge to improve the accessibility of services.