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In the randomized, placebo-controlled PREVENT-19 phase 3 trial conducted in the U.S. and Mexico of the NVX-CoV2373 adjuvanted, recombinant spike protein nanoparticle vaccine, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks after two doses were assessed as correlates of risk and as correlates of protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID- 19). These immune correlates analyses were conducted in the U.S. cohort of baseline SARS- CoV-2 negative per-protocol participants using a case-cohort design that measured the antibody markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases (Mexico was excluded due to zero breakthrough cases with the efficacy data cut-off date April 19, 2021). In vaccine recipients, the baseline risk factor-adjusted hazard ratio of COVID-19 was 0.36 (95% CI: 0.20, 0.63), p<0.001 (adjusted p-0.005) per 10-fold increase in IgG spike concentration and 0.39 (0.19, 0.82), p=0.013 (adjusted p=0.030) per 10-fold increase in nAb ID50 titer. At spike IgG concentration 100, 1000, and 6934 binding antibody units/ml (100 is the 3rd percentile, 6934 is the 97.5th percentile), vaccine efficacy to reduce the probability of acquiring COVID-19 at 59 days post marker measurement was 65.5% (95% CI: 23.0%, 90.8%), 87.7% (77.7%, 94.4%), and 94.8% (88.0%, 97.9%), respectively. At nAb ID50 titers of 50, 100, 1000, and 7230 IU50/ml (50 is the 5th percentile, 7230 the 97.5th percentile), these estimates were 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), 92.8% (85.1%, 97.4%) and 96.8% (88.3%, 99.3%). The same two antibody markers were assessed as immune correlates via the same study design and statistical analysis in the mRNA-1273 phase 3 COVE trial (except in COVE the markers were measured four weeks post dose two). Spike IgG levels were slightly lower and nAb ID50 titers slightly higher after NVX-CoV2373 than after mRNA-1273 vaccination. The strength of the nAb ID50 correlate was similar between the trials, whereas the spike IgG antibodies appeared to correlate more strongly with NVX-CoV2373 in PREVENT-19, as quantified by the hazard ratio and the degree of change in vaccine efficacy across antibody levels. However, the relatively few breakthrough cases in PREVENT-19 limited the ability to infer a stronger correlate. The conclusion is that both markers were consistent correlates of protection for the two vaccines, supporting potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.
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Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
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BackgroundIn the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. MethodsThrough case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. ResultsDay 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). ConclusionsBinding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. Trial registration numberCOVE ClinicalTrials.gov number, NCT04470427
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Objective@#To investigate the influencing factors of smoking tendency of adolescents and to analyze the influence of e-cigarette on smoking tendency of teenagers and the possible interaction, to provide evidence for tobacco control measures.@*Methods@#Stratified multistage cluster probability sampling method was used to select 6 178 students from junior middle school, high school and vocational high school students in Shanghai for questionnaire survey from September to October 2019. Students with smoking tendency were taken as case group, adolescents with same sex and similar age(within 1 year) were mathed in 1∶3 ratio. A total of 631 adolescents with smoking tendency and 1 870 non-smoking tendency were included in the study. Conditional Logistic regression was used to analyze the influencing factors and possible interactions.@*Results@#After adjusting gender, age and other covariates, conditional Logistic analysis results showed that the smoking tendency of middle school students was associated with factors such as their friends smoking, trying cigarettes and trying e-cigarettes. The OR value and 95%CI were 3.26(2.47-4.29), 5.90(3.76-9.24), and 3.28(2.11-5.10), respectively. The interaction analysis results showed that the OR value and 95%CI of the multiplying interaction between friends smoking and trying e-cigarettes, trying smoking and trying e-cigarettes were 8.62(4.90-15.17) and 12.01(6.02-23.95), respectively. There was no additive interaction.@*Conclusion@#Tobacco control interventions, such as e-cigarette harm publicity and peer education, can help to change teenagers smoking tendency and further reduce their tobacco use rate.
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OBJECTIVE： To investigate in vitro release rate and in vivo pharmacokinetics of Resveratrol/hydroxypropyl-β- cyclodextrin/chitosan sustained-release pellets （RES/HP-β-CD/Chitosan） in rats. METHODS： In vitro release rate of RES raw materials， RES-HP-β-CD complexes （RES/HP-β-CD） and RES/HP-β-CD/Chitosan in water within 12 h were investigated by paddle method. The pharmacokinetic characteristics of RES raw materials， RES/HP-β-CD and RES/HP-β-CD/Chitosan were compared within 720 min after intragastric administration. RESULTS： Compared with RES raw materials， in vitro release rate of RES/HP-β-CD was increased significantly， and 120 min accumulative release rate reached 87％. Compared with RES/HP-β-CD， in vitro release rate of RES/HP-β-CD/Chitosan were relieved significantly； release time prolonged significantly； 12 h accumulative release rate was 72％. The pharmacokinetic parameters of RES raw materials， RES/HP-β-CD and RES/HP-β-CD/Chitosan included that cmax were 473.3， 2 492.2， 590.5 ng/mL； t1/2 were 2.6， 0.5， 4.6 h； AUC0-12 h were 514.7， 824.6， 2 778.5 ng·h/mL. Compared with RES raw materials， relative bioavailability of RES/HP-β-CD and RES/HP-β-CD/Chitosan were 172.5％ and 540.0％. CONCLUSIONS： RES/HP-β-CD/Chitosan shows good sustained-release effect， and its bioavailability is significantly higher than that of RES raw materials， RES/HP-β-CD.
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OBJECTIVE： To prepare Resveratrol-hydroxypropyl-β-cyclodextrin-chitosan sustained-release pellets （RES-HP-β- CD-Chitosan）， and to characterize it. METHODS： Resveratrol raw material， HP-β-cyclodextrin and chitosan were collected with ratio of 1 ∶ 7 ∶ 0.25. Resveratrol-HP-β-cyclodextrin inclusion compound were prepared by solvent method， and then added into chitosan， RES-HP-β-CD-Chitosan were prepared by spray drying method. Particle size of prepared sustained-released pellets were observed by optical microscope. X-ray， DSC， IR and SEM were used to characterize RES-HP-β-CD-Chitosan. The contents of resveratrol in prepared sustained-released pellets were determined by UV spectrum， and drug-loading amount and encapsulation efficiency were calculated. RESULTS： Particle size of prepared RES-HP-β-CD-Chitosan was （2.23±0.35） μm （n＝300）. Characterization results show that RES-HP-β-CD-Chitosan was spherical in shape； shrinkage was found on the surface of microspheres， and resveratrol was included in HP-β-cyclodextrin in molecule or amorphous state. Drug-loading amount of prepared RES-HP-β-CD-Chitosan was 11.67％ （n＝3）， encapsulation efficiency was 96.27％ （n＝3）. CONCLUSIONS： RES-HP-β-CD- Chitosan is prepared successfully.
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Objective To analyze the characteristics of SCI papers published in international cooperation of Chinese medicine and to understand the current research situation in this field.Methods Using the scientific citation index extension (SCI-E) database in Web of Science was used as the data source,and this paper retrieves retrieved related papers and highly cited papers on the international cooperation of traditional Chinese medicine during the year 1990-2017,and analyses from the years,cooperative countries and regions,periodicals,fund support,authors' institutions and research content by using the method of Bibliometrics and co co-word clustering.Results The total number of the articles for analyzing was 10 984,and the number of highly cited article was 114,which showed the number of article increased gradually.There are were 145 countries and regions in cooperation.The first three countries are were the United States,Japan and the United Kingdom.A total of 25 core periodicals are were determined.The fund funding rate wais 74.5％.The fund financed institutions with the largest number of cooperative contributions are were both the National Natural Science Foundation of China and the National Institutes of health in the United States.The hot top-subject of cooperative research haswas pharmacology and pharmacology.The breast cancer,ovarian cancer,colorectal cancer and inflammation,such as acupuncture treatment for pain,polycystic ovary syndrome,and depression.Conclusions The international cooperation of traditional Chinese medicine has gone through the embryonic stage,and now it is at the stage of development.
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@#The application and advance of somatic sense interactive devices, such as EyeToy, Wii and Kinect, in the motor rehabilitation were introduced in this paper. The prospect of application of somatic sense interactive technology as an effective approach in rehabilitation is wide and bright.
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Objective To evaluate the effect of curcumin on the inflammatory responses in the hippocampus during global cerebral ischemia-reperfusion (I/R) injury in hypertensive rats.Methods Forty-eight SPF male Wistar-Kyoto rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 2 groups (n =24 each) using a random number table:sham operation group (W-Sham group) and I/R group (W-I/R group).Seventy-two SPF male spontaneously hypertensive rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (S-Sham group),I/R group (S-I/R group),and curcumin group (S-Cur group).Global cerebral ischemia was induced by 4-vessel occlusion method (10 min of transient global ischemia followed by reperfusion).Curcumin 100 mg/kg was injected intraperitoneally at 30 min of reperfusion in S-Cur group,and corn oil 5 ml/kg was injected intraperitoneally at 30 min of reperfusion in the other groups.The ability of learning and memory was tested by step-down test at 7 days of reperfusion.Rats were sacrificed at 3 h and 1,3 and 7 days of reperfusion (T1-4) and the hippocampi were removed.The morphological changes of pyramidal cells in hippocampal CA1 area were observed by HE staining.The mean density of pyramidal cells in hippocampal CA1 area was quantified by Nissl staining.The contents of interleukin-lβ (IL-1β),tumor necrosis factor-alpha (TNF-α) and IL-10 in the hippocampus were determined by ELISA.Results Compared with W-Sham group,the ability of learning and memory was significantly decreased,the mean density of pyramidal cells in hippocampal CA1 area was decreased,the contents of IL-1β at T1-3,TNF-α at T1,and IL-10 at T2 were increased,and the contents of IL-10 were decreased at T1,3,4 in W-I/R group,and no significant changes were found in the parameters mentioned above in S-Sham group.Compared with W-I/R group,the ability of learning and memory was significantly decreased,the contents of IL-1β at T1,3 and IL-10 at T2 were decreased,the content of TNF-α was increased at T1,no significant change was found in the mean density of pyramidal cells in hippocampal CA1 area,and the damage to pyramidal cells in hippocampal CA1 area was severe in S-I/R group.Compared with S-I/R group,the ability of learning and memory was significantly increased,the mean density of pyramidal cells in hippocampal CA1 area was increased,the contents of IL-1β at T2,3 and TNF-α at T1-4 were increased,and the content of IL-10 was increased at T2,and the damage to pyramidal cells in hippocampal CA1 area was reduced in S-Cur group.Conclusion Inhibition of inflammatory responses in the hippocampus may be involved in the mechanism by which curcumin reduces global cerebral I/R injury in hypertensive rats.
