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BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
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Aged , Humans , Antibodies, Viral , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Immunization, Passive , Recombinant Fusion Proteins , SARS-CoV-2ABSTRACT
Objective::To predict the action targets of anti-lung cancer active ingredients of Xiao Chaihutang, in order to explore the " multi-components, multi-targets and multi-pathways" mechanism using network pharmacology. Method::The active ingredients of Xiao Chaihutang that obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), traditional Chinese medicine integrative database for herb molecular mechanism analysis(TCMID) and literature were used to predict the targets by the reversed pharmacophore matching method.To screen out optimization targets, we chose elbow point analysis by using self-developed software TCMKD1.0, and screened out lung cancer-related targets by searching databases, such as Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man(OMIM) and GeneCards, and reviewing literatures.Then components-target network, protein-protein interaction network and targets-pathways network were constructed.The pathway information was acquired with STRING.The Cytoscape 3.6 software was used to construct the ingredients-targets-pathways network of Xiao Chaihutang. Result::The 162 active components in Xiao Chaihutang were obtained, involving 71 anti-lung cancer targets and 11 related pathways.Through topological network analysis, 96 important components, such as quercetin, ginsenosideRh2, formononetin and β-sitosterol were obtained, 28 key targets, such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (KDR), cysteine protease-3 (Caspase-3), mitogen-activated protein kinase1(MAPK1), hepatocyte growth factor (MET) were received, and 61 core pathways, such as non-small cell lung cancer, small cell lung cancer, ErbB signaling pathway, VEGF signaling pathway were acquired. Conclusion::The result suggests that the active components of Xiao Chaihutang against lung cancer may include quercetin, ginsenoside Rh2, 6-shogaol, formononetin, β-sitosterol.And the mechanism may be related to ErbB signaling pathway, MAPK signaling pathway and VEGF signaling pathway.This research provides a scientific basis for further elucidation of the anti-lung cancer pharmacological mechanism of Xiao Chaihutang.
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Objective:To investigate the changes of genus-level gut microbiome in patients with spinal cord injury and its significance in clinical rehabilitation. Methods:Fecal samples were collected from 23 patients with spinal cord injury (patients group) and 21 healthy volunteers (control group). Gut microbiome was detected by 16S rDNA high-throughput sequencing. Bioinformatics methods such as species composition analysis and Random Forest were used to analyze the distribution and difference of genus-level gut microbiome between two groups. Results:Compared with the control group, the increased important marker genera in the patients group were as follows: UBA1819, Ruminiclostridium 9, Ruminococcaceae NK4A214 group, Ruminococcus 2, Ruminococceae UCG-005, Ruminiclostridium 5, Flavonifractor belonging to Ruminococceae; Aglistes, dgA-11 gut group, Rikenaceae RC9 gut group belonging to Rikenellaceae; [Eubacterium] oxidoreducens group belonging to Lachnospiraceae; Intestinibacter belonging to Peptostreptococcaceae; Escherichia-Shigella belonging to Enterobacteriaceae; Tannerellaceae belonging to Parabacteroides (|U| > 1.962, P < 0.05). The decreased marker genera in the patients group was Fusobacterium of Fusobacteriaceae (|U| = -2.284, P < 0.05). Conclusion:There are significant differences of gut microbiome in spinal cord injury patients. The relative abundance of Ruminococcaceae relating to depression, Ruminococcus relating to central nervous system diseases, and enteropathogenic bacteria such as Escherichia-Shigella and Erysipelothrix increase; and the relative abundance of butyrate-producing bacteria and anti-inflammatory bacteria benefitting to the intestine decrease; which may play a role in clinic.
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IκB kinase beta (IKKbeta) is a key kinase in nuclear factor kappa B (NF-kappaB) signaling pathway. After spinal cord injury, IKKbeta is activated, and the signal pathway of NF-kappa B is abnormally activated, which produces a large number of inflammatory factors, which has a negative impact on the recovery of spinal cord injury. This article mainly summarized the structure and function of IKKbeta and its application in inflammatory reaction after spinal cord injury, trying to find a new target for the treatment of spinal cord injury.
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Transcranial direct current stimulation regulates nerve cell transmembrane potential through current, leading to depolarization or hyperpolarization, and changes the excitability of cerebral cortex, thus improving neuropathic pain after spinal cord injury. This article mainly reviewed mechanism, clinical application, safety and limitation of transcranial direct current stimulation to neuropathic pain after spinal cord injury.
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Objective: To set a criterion for determining whether herbs distribute to kidney meridian from the perspective of tissue expression of protein receptors, so as to provide new ideas and a new method for the quantitative study of meridian tropism. Method: The 9 Yang-tonifying herbs were selected as the training set, and 2 Yang-tonifying herbs were used as the verification set. The TCMSP2.3,PubChem,Uniprot and other database were used to collect the active compounds and targets of traditional Chinese medicine(TCM). The core target proteins of Yang-tonifying herbs were obtained by using the Maximum Similarity Algorithm for TCM in the training set. The THPA database was used to collect expressions of tissues and target proteins. The empirical regression equation was constructed to explore the tissue distribution of the receptors in the training set, and the criterion for determining whether herbs distribute to kidney meridian was established. The criteria model was tested through validation set data. Result: The herb-active ingredient-protein receptor-tissue expression data library was constructed. A total of 39 core target proteins of Yang-tonifying herbs were acquired. The equations in the training set were highly consistent, with no statistical difference (P=0.999 7). The data of the combined training set was finally fitted to a judgment equation. The model was successfully tested with herbs in the validation set. The accuracy of the model was 100%. Conclusion: This study explored a new method for judging whether TCM distributes to kidney meridian, established an effective criterion model and verified the reliability of the new method. It provides a theoretical basis for the modernization of meridian tropism of traditional Chinese medicine, and is of great significance for the rapid development of traditional Chinese medicine.
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<p><b>OBJECTIVE</b>We aimed to analyze the impact of cardiovascular disease (CVD) deaths on life expectancy (LE) in Chinese population and estimate the percentage reduction in CVD mortality needed to increase LE by 1 year from the current level, a national target of health improvement.</p><p><b>METHODS</b>We used life tables, cause-elimination life tables, and age decomposition of LE with corrected mortality data from the National Disease Surveillance System in 2010.</p><p><b>RESULTS</b>LE at birth of Chinese people was 73.24 years in 2010. Women had a longer LE than men, and urban population had a longer LE than rural population. CVD deaths resulted in a 4.79-year LE loss and premature deaths in people aged 25 to 64 years were responsible for a substantial part of LE loss from CVD. Death from ischemic heart disease and cerebrovascular diseases accounted for 69.2% of LE loss from CVD deaths and death from cerebrovascular diseases was the largest contributor. In rural men, 51.1% LE loss from CVD deaths was caused by cerebrovascular diseases. If there were no changes in mortality rates for all other diseases, a 27.4% reduction in CVD mortality would increase LE by 1 year in Chinese population.</p><p><b>CONCLUSION</b>There is a considerable impact of CVD deaths on LE. A 1-year LE increase in the future requires at least a 27.4% reduction in CVD mortality from the current level. Targeting the rural population and tackling cerebrovascular diseases are important for reaching the national goal of health improvement.</p>
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Cardiovascular Diseases , Mortality , China , Epidemiology , Life Expectancy , Life Tables , Rural Population , Urban PopulationABSTRACT
<p><b>OBJECTIVE</b>To evaluate the impact of cerebrovascular disease mortality on life expectancy (LE) in China in 2010 compared with 2005, and to identify the high-risk population (age, sex, and region) where cerebrovascular disease mortality has had a major impact on LE.</p><p><b>METHODS</b>LE and cause-eliminated LE were calculated by using standard life tables which used adjusted mortality data from the Death Surveillance Data Sets in 2005 and 2010 from the National Disease Surveillance System. Decomposition was used to quantitate the impact of cerebrovascular disease in different age groups.</p><p><b>RESULTS</b>LE in China was 73.24 years in 2010, which was higher in women and urban residents compared with men and rural residents. The loss of LE caused by cerebrovascular disease mortality was 2.26 years, which was higher in men and rural residents compared with women and urban residents. More than 30% of the loss of LE were attributed to premature death from cerebrovascular disease in people aged <65 years. Compared with 2005, LE in 2010 increased by 0.92 years. The reduction of cerebrovascular disease mortality in urban residents contributed 0.45 years to the increase of LE, but the increase of cerebrovascular disease mortality caused a 0.12-year loss of LE in rural residents.</p><p><b>CONCLUSION</b>Cerebrovascular disease mortality had a major impact on LE in China, with a significant difference between urban and rural residents. LE is likely to be further increased by reducing cerebrovascular disease mortality, and special attention should be paid to reducing premature deaths in people aged <65 years.</p>
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Cerebrovascular Disorders , Mortality , China , Epidemiology , Life Expectancy , Rural Health , Rural Population , Urban PopulationABSTRACT
<p><b>OBJECTIVE</b>To establish a highly sensitive fluorometric nanobiosensor for determination of aqueous mercury ions (Hg(2+)) using optimized mercury-specific oligonucleotide (MSO) probes and graphene oxide (GO).</p><p><b>METHODS</b>The nanobiosensor was assembled by attaching the self-designed MSO(1) (5' end labeled with fluorophore carboxyfluorescein (FAM), denoted as FAM-MSO(1)) and MSO(2) to the surface of GO through strong non-covalent bonding forces. Upon the addition of Hg(2+), the formation of the T-Hg(2+)-T configuration desorbed the FAM-MSO(1) and MSO(2) from the surface of GO, resulting in a restoration of the fluorescence of FAM-MSO(1). Using the specific mispairing of T-Hg(2+)-T and the changes in fluorescent signals in solutions, quantitative analysis of Hg(2+) could be performed.</p><p><b>RESULTS</b>The average thickness of the prepared GO sheets was only 1.4 nm. For the Hg(2+) nanobiosensor, the optimum concentrations of FAM-MSO(1) and MSO(2) were both 1 µmol/L, the optimum volume of 0.5 g/L GO was 5 µL, and the limit of detection was 10 pmol/L; it had low cross-reactivity with 10 other kinds of non-specific metal ions; the fluorescence recovery efficiency was up to 65% in the re-determination of Hg(2+) after addition of Na(2)S(2)O(3).</p><p><b>CONCLUSION</b>The MSO/GO-based nanobiosensor is convenient to operate, highly sensitive, highly specific, highly accurate, and reusable. It can be applied to determine trace amount of Hg(2+) in aqueous solutions.</p>
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Biosensing Techniques , Fluorometry , Graphite , Mercury , Nanotechnology , Oligonucleotide Probes , WaterABSTRACT
<p><b>OBJECTIVE</b>To develop a nanobiosensor for rapid colorimetric detecting Mercury (II) Ions (Hg(2+)) in water by mercury-specific oligonucleotides (MSOs) probe and gold nanoparticles.</p><p><b>METHODS</b>The nanobiosensor was assembled by adsorbing the optimized MSOs on the surface of gold nanoparticles. A direct colorimetric probe of Hg(2+) which relied on the T-T mismatches in DNA duplexes was used to selectively and strongly capture Hg(2+). Hg(2+) induces the aggregation of gold nanoparticles with appropriate amount of salts, resulting the color change (red to blue).</p><p><b>RESULTS</b>The diameter and concentration of the gold nanoparticle preparation were 15 nm and 2.97 nmol/L, respectively. Truncated MSOs (9 bp) showed the similar Hg(2+)-binding activity. The optimum concentration of the NaNO3 solution was 0.5 mol/L. The nanobiosensor could detect Hg(2+)in a range of 10 ∼ 1000 µmol/L within few minutes and the specificity was 100%.</p><p><b>CONCLUSION</b>A new nanobiosensor is developed successfully for rapid colorimetric detecting Hg(2+) in water, avoiding either MSOs labeling or gold nanoparticles modification. This technique is simple, convenient and rapid detecting method with high sensitivity and specificity.</p>
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Biosensing Techniques , Methods , Ions , Mercury , Metal Nanoparticles , WaterABSTRACT
<p><b>OBJECTIVE</b>To describe the distribution characteristics of carotid atherosclerosis and to analyze its association with cardiovascular risk factors in middle-aged and elderly Chinese.</p><p><b>METHODS</b>In 2007, the second cross-sectional examination for cardiovascular risk factors and B-mode ultrasound imaging on carotid arteries were performed in a Chinese population consisting of 2681 subjects aged 43-81 years old from two cohorts participants of the People's Republic of China/United States of America collaborative study (USA-PRC study) and the Chinese multi-provincial cohort study (CMCS). The association of cardiovascular risk factors with intima-media thickening (ITM) and plaque of carotid arteries was analyzed.</p><p><b>RESULTS</b>(1) The mean intima-media thickening (Mean-IMT) of carotid artery was 0.68 mm, the maximal intima-media thickening (Max-IMT) was 1.07 mm. (2) The prevalence rate of carotid plaque was 60.3% in all subjects. As for the different sites of carotid arteries, the plaque prevalence rate at carotid bulb was 61.2% for male and 51.6% for female (chi2 = 23.44, P < 0.01), and at the internal carotid artery was 24.7% for male and 12.2% for female (chi2 = 69.57, P < 0.01), at the common carotid artery was 20.9% for male and 13.8% for female (chi2 = 23.18, P < 0.01). (3) After adjusting for age and other cardiovascular risk factors, the Mean-IMT and Max-IMT increased with elevated levels of systolic blood pressure, plasma glucose and low density lipoproteins cholesterol (LDL-C) (all P < 0.05). Hypertension, diabetes, smoking and high LDL-C (P < 0.05) were independent predict factors for the risk of carotid plaque.</p><p><b>CONCLUSION</b>The carotid atherosclerosis was common in middle and older age Chinese and was positively associated with classical cardiovascular disease risk factors.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Age Distribution , Carotid Artery Diseases , Diagnostic Imaging , Epidemiology , China , Epidemiology , Cohort Studies , Cross-Sectional Studies , Prevalence , Risk Factors , Ultrasonography , United States , EpidemiologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the prediction value of blood lipid levels on the newly-identified carotid plaque in middle-aged and elderly Chinese population.</p><p><b>METHODS</b>All study subjects were recruited from two cohorts from 2002 to 2007 [the People's Republic of China/United States of America collaborative study (USA-PRC study) and the Chinese multi-provincial cohort study (CMCS)]. The baseline examination including cardiovascular disease risk factors and B-mode ultrasound of carotid artery was performed in 2002 and the second examination was made in September to October, 2007. The relationship between baseline lipids and carotid plaque incidence was analyzed in a total of 2000 subjects aged 47 to 79 years (mean 63 years).</p><p><b>RESULTS</b>(1) During these 5 years, the prevalence of carotid plaque increased from 30.3% to 62.2% and from 21.5% to 51.5% for men and women, respectively. The newly-identified carotid plaque incidence was 41.8% for men and 34.1% for women. (2) The incidence of artery plaque significantly increased in both sexes in proportion to increase of baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and total to high-density cholesterol ratio (TC/HDL-C) levels (P < 0.05 or P < 0.01). (3) Cross-stratification analysis of LDL-C, triglyceride (TG) and HDL-C for carotid plaque incidence indicated the existence of conjoint effects between LDL-C and HDL-C, LDL and TG, as well as between TG and HDL-C, on the increased incidence of carotid plaque. (4) Multi-factorial analysis showed that higher LDL-C, non-HDL-C and TC/HDL-C were independent risk factors for development of new carotid plaque [OR = 1.44 (95%CI = 1.07 - 1.94), OR = 1.45 (95% CI = 1.08 - 1.96), OR = 1.59(95% CI = 1.14 - 2.23) in men;OR = 1.47 (95% CI = 1.13 - 1.92), OR = 1.35 (95% CI = 1.04 - 1.75), OR = 1.64 (95% CI = 1.20 - 2.23) in women].</p><p><b>CONCLUSIONS</b>The prevalence of carotid plaque increased rapidly in this cohort between 2002 and 2007. Elevated LDL-C, non-HDL-C and TC/HDL-C levels were independent predictors of newly developed carotid plaque.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People , Carotid Arteries , Diagnostic Imaging , Carotid Stenosis , Blood , Diagnostic Imaging , Cholesterol , Blood , Cohort Studies , Lipids , Blood , Predictive Value of Tests , Risk Factors , Triglycerides , Blood , UltrasonographyABSTRACT
The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1/S phase transition. The number of target cells was found to increase in phase G0/G1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer.
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Objective To study the correlation between obesity and clustering of major risk factors on cardiovascular disease in the elderly.Methods A cross-sectionai study was conducted.Data from 546 elderlY aged 60-90 were analyzed for the relationship between obesity and clustering of risk factors for cardiovascular diseases,with descriptive statistical methods,x2 test,logistie regression and ROC curve．Results (1)The positive rates of the four major risk factors and clustering appeared an upward trend along with the BMI and or the wc.The overall positive rate of clustering of risk factors among the total 546 elderly people was 59.5％,and 52.5％in males,65.7％in females.(2)As compared with females,males had a higher growth rate of clustering with the elevating of BMI and WC.and odds ratios of the highest-level groups were 13.579 and 2.876 in males and females.Respectively.(3)Both BMI and WC were independent influencing factors for male(P<0.05),and logistic regression coefficients were 0.196 and 0.074 for BMI and WC,respectively.Only WC appeared to be the independent influencing factor for females(P<0.05),while BMI WaS not(P:0.537),with logistic regression coefficient as 0.060 for WC.(4)The combination equation of male's BMI and WC Was CEBMI+WC=0.726 × BMI+0.274 × WC,with the optimum cut-off value as 41.59,and the sensitivity and the specificity were 0.785 and 0.598,respectively．Conclusion Four major risk factors for cardiovascular diseases were often related to obesity while control of BMI and WC were of great significance to the primary prevention of cardiovascular disease．The combined equation of BMI and WC could be used to predict the risk of clustering.
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Three hundred and twenty-one bacteria strains were obtained from rice leaves,stem,root tissue and paddy field soil,of which the number of strains which can inhibit mycelium of Magnaporthe grisea growth markedly was fifty-seven through fermentation in 2.0 mL Eppendorf tube,and among these fifty-seven strains,five strains were strongly antagonistic to Magnaporthe grisea.These five strains was identified for their morphologic,physiological and biochemical characteristics,and the results showed that one strain(No.156)was bacillus subtilis,two strains(No.171 and No.177)were Bacillus pumillus and two strains(No.192 and No.279)were Bacillus ploymyxa.