Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen

BackgroundRising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10g V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. MethodsWe conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10g V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. ResultsThe third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10g V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. ConclusionsA homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

Effectiveness of a home-based exercise program among patients with lower limb spasticity post-stroke: A randomized controlled trial

Purpose@#To evaluate the effectiveness of advanced practice nurse–guided home-based rehabilitation exercise program (HREPro) among patients with lower limb spasticity post-stroke. @*Methods@#This randomized controlled study recruited 121 patients with lower limb spasticity post-stroke. Intervention (n = 59) and control (n = 62) groups underwent 12-month HREPro and conventional rehabilitation, respectively, after discharge. The Fugl–Meyer assessment of spasticity measurement, modified Ashworth scale of motor function, 10-Meter Walk Test of walking ability, and Barthel index of activities of daily living (ADL) were evaluated at 0, 3, 6, and 12 months after discharge. @*Results@#Significant differences were found in spasticity degree, motor function, walking ability, and ADL at 6 and 12 months after discharge between the control and intervention groups. Lower limb spasticity and ADL in the intervention group were significantly improved. @*Conclusion@#HREPro is effective for rehabilitation of patients with lower limb spasticity post-stroke and has favorable home application.

Effectiveness of a home-based exercise program among patients with lower limb spasticity post-stroke: A randomized controlled trial

Purpose@#To evaluate the effectiveness of advanced practice nurse–guided home-based rehabilitation exercise program (HREPro) among patients with lower limb spasticity post-stroke. @*Methods@#This randomized controlled study recruited 121 patients with lower limb spasticity post-stroke. Intervention (n = 59) and control (n = 62) groups underwent 12-month HREPro and conventional rehabilitation, respectively, after discharge. The Fugl–Meyer assessment of spasticity measurement, modified Ashworth scale of motor function, 10-Meter Walk Test of walking ability, and Barthel index of activities of daily living (ADL) were evaluated at 0, 3, 6, and 12 months after discharge. @*Results@#Significant differences were found in spasticity degree, motor function, walking ability, and ADL at 6 and 12 months after discharge between the control and intervention groups. Lower limb spasticity and ADL in the intervention group were significantly improved. @*Conclusion@#HREPro is effective for rehabilitation of patients with lower limb spasticity post-stroke and has favorable home application.

Early intervention for severe stenosis of non-infarct related artery in patients with acute ST-segment elevation myocardial infarction and multi-vessel disease / 实用医学杂志

Objective To explore the clinical feasibility and safety of early intervention for severe stenosis of non-infarct related artery(non-IRA)in patients with acute ST-segment elevation myocardial infarction(STEMI) and multi-vessel disease(MVD)after successful primary percutaneous coronary intervention(PCI)for infarct-asso-ciated artery(IRA). Methods From May 1st,2011 to December 30th,2016,165 patients with STEMI and MVD were enrolled in our study. After the completion of primary PCI in IRA ,75 patients still in the hospital agreed to undergo a second staged PCI in severe stenosis of non-infarct arteries. We analyzed the in-hospital adverse events ,the length of hospital stay and clinical outcomes during the follow-up in the study population. Results There was no significant difference in the incidence of adverse events between the two groups during hos-pitalization. However,compared to patients treated with the IRA-only PCI,those treated with early intervention for severe stenosis of non-IRA was associated with greater benefits for clinical outcomes(including rehospitalization for heart failure,rehospitalization for ACS,recurrent angina pectoris,necessity for reintervention)during the follow-up except for the all-cause mortality. Conclusion Early intervention for severe stenosis of non-IRA is a feasible and safe procedure in patients with acute STEMI and MVD after successful primary PCI.

Curative effect of benidipine hydrochloride on patients with coronary slow flow angina pectoris / 中国综合临床

Objective To investigate the curative effect of benidipine hydrochloride on patients with coronary slow flow angina pectoris(CSFA).Methods Sixty cases patients with CSFA were randomly divided into two groups of 30 patients each.In the control group patients were received aspirin(100 mg,1 times/d) and atorvastatin(20 mg,1 times/d) as basic treatment;in the treatment group patients were received basic treatment plus benidipine hydrochloride(4 mg,1 times/d).Follow up for 6 mouths,the effectiveness rate of treatment(relief of angina and electrocardiogram of myocardial ischemia),the correction of thrombolysis in myocardial infarction(TIMI) frame count(CTFC) before and after the different intervention,and the incidence of adverse cardiovascular events were compared between the treatment group and the control group.Results The effectiveness rate of treatment in the treatment group(86.7%,26/30) was significantly higher than that in the control group(63.3%(19/30);χ2=4.356,P=0.037).There were significant reductions of CTFC in both groups after the different intervention(treatment group:(28.43±3.95) frames vs.(18.40±3.73) frames,t=10.254,P=0.000;control group:(27.87±4.14) frames vs.(21.87±4.17) frames,t=5.580,P=0.000).There was more significant reductions of CTFC in the treatment group as compared to the control group(t=2.138,P=0.037).The incidence of adverse cardiovascular events in the treatment group(10.0%(3/30)) was significantly lower than that in the control group(33.3%(10/30),P=0.028).Conclusion Benidipine hydrochloride is effective in the treatment of CSFA.

Advancement on the use of percutaneous mechanical circulatory support devices in severe cardiovascular diseases / 中华危重病急救医学

Percutaneous mechanical circulatory support (PMCS) devices are effective in the treatment of patients with cardiogenic shock and acute decompensated heart failure, as a bridge to the recovery of heart function or further treatment. The intra-aortic balloon pump (IABP) is now the most widely used PMCS. New PMCS devices including Transseptal device of Tandem-Heart, transaortic valve device of Impella and extracorporeal membrane oxygenation (ECMO) might provide more effective hemodynamic supports. Doctors should choose appropriate PMCS devices and their working modes, according to patient's clinical conditions, based on the working principles and hemodynamic effects of the devices, in order to achieve the best effects and help patients live through the crisis of diseases.

Association between ambulatory blood pressure levels and blood pressure variability with myocardial performance index in untreated hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the association between ambulatory blood pressure levels and blood pressure variability (BPV) with myocardial performance index (MPI) in untreated hypertensive patients.</p><p><b>METHODS</b>From January to September 2013, a total of 81 untreated hypertensive patients were included in this study. All patients received ambulatory blood pressure monitoring and echocardiography measurements. MPI was determined in all patients by the following formula: MPI = (isovolumic contraction time + isovolumic relaxation time)/ejection time. The patients were divided into two groups according to left ventricular MPI: patients with MPI < 0.47 (n = 39) and patients with MPI ≤ 0.47 (n = 42). The mean levels and standard deviation (SD) of 24 h, daytime and nighttime blood pressures were compared between the two groups. SD was used to express BPV. Determinants of MPI were identified by multivariate regression analysis.</p><p><b>RESULTS</b>24 h and daytime systolic blood pressure, 24 h, daytime and nighttime diastolic blood pressure, as well as SD of 24 h and daytime systolic blood pressure ((130.1±8.7), (134.0±8.2), (89.1±6.3), (90.9±6.4), (83.1±9.9), (13.7±3.3) and (14.2±3.5) mmHg (1 mmHg = 0.133 kPa), respectively) were significantly higher in patients with MPI > 0.47 than those ((124.8±8.7), (126.7±8.8), (84.5±7.1), (86.2±7.4), (76.4±7.5), (11.8±2.1) and (10.4±1.9) mmHg, respectively) in patients with MPI ≤ 0.47 (all P < 0.05). Multivariate regression analysis showed that 24 h diastolic blood pressure (β = 0.239, P = 0.007) and SD of 24 h systolic blood pressure (β = 0.333, P < 0.001), left ventricular mass index and early diastolic mitral annular velocity were independently associated with MPI.</p><p><b>CONCLUSION</b>The increase of diastolic blood pressure and systolic BPV are associated with the deterioration of left ventricular function.</p>

Impact of diabetes and stress hyperglycemia on thrombolytic effect and prognosis in patients with acute cerebral infarction / 中国脑血管病杂志

Objective To observe the impact of diabetes and stress hyperglycemia on thrombolytic effect and short-term prognosis in patients with acute cerebral infarction. Methods A total of 127 patients with acute cerebral infarction (≤4. 5 h) who received thrombolytic therapy with alteplase at General Hospital of Beijing Military Command from January 2012 to August 2013 were enrolled retrospectively. They were divided into three groups:Diabetes group (n=35),stress hyperglycemia group (n=49),and normal glucose group (n=43) according to whether they had a history of diabetes,random glucose on admission, and oral glucose tolerance test at day 7. At 24 h after thrombolysis,the National Institute of Health Stroke Scale (NIHSS) scores,recanalization rate,and the modified Rankin Scale (mRS) scores at day 90 were compared between the 2 groups. Results Before thrombolysis,the NIHSS scores of the diabetic group, stress hyperglycemia group,and normal glucose group were 14. 2 ± 5. 1,12. 8 ± 5. 6,and 13. 0 ± 4. 6,respectively (P>0.05);at 24 h after thrombolysis,they were 14.7 ±6.0,11.9 ±4.9,and 8.0 ±2.9,respectively (P0. 05);the NIHSS score of the normal glucose group was lower than before thrombolysis. There was significant difference (P <0. 05). After thrombolysis,the patients with good recanalization were 54. 3% (n=19),57. 1% (n=28),and 67. 4% (n=29),respectively in the three groups;the hemorrhagic conversion rate was 14. 3% (n=5),6. 1% (n=3),and 2. 3% (n=1),respectively. There were no significant differences. At day 90 after thrombolysis,the mRS scores in the 3 groups showed that the good prognosis rate of the normal glucose group was 72. 1% (n=31);it was significantly higher than 51. 0% (n=25) of the stress hyperglycemia group and 29. 6% (n=10) of the diabetes group. There were significant differences (P<0. 05,P<0. 01). There was also significant difference between the stress hyperglycemia group and the diabetes group. Conclusion Diabetes and stress hyperglycemia have varying degrees of adverse effects on the efficacy and prognosis of the thrombolytic therapy for acute cerebral infarction.

Association of serum angiopoietin-1 and angiopoietin-2 with ST-segment resolution in acute ;myocardial infarction patients treated with primary percutaneous coronary intervention / 中国介入心脏病学杂志

Objective To investigate the association of serum angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) with myocardial reperfusion in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods A total of 103 consecutive STEMI patients who received primary PCI were enrolled in this study. The patients were divided into two groups according to ST-segment resolution (STR) at 2 h after PCI:STR ≥ 50%group (n=69) and STR0.05). In multivariable logistic regression analysis, Ang-2/Ang-1 before PCI was independently associated with STR < 50%;Other independent predictors were pain to balloon time, infarct related artery (LAD), and TIMI flow grade<Ⅲafter PCI. Conclusions Higher Ang-2/Ang-1 is an independent predictor of poor myocardial reperfusion in STEMI patients after PCI.

Velocity vector imaging combined with contrast echocardiography in evaluation of relationship between myocardial perfusion and diastolic function in dog models of coronary artery stenosis / 中国医学影像技术

Objective To evaluate the relationship between myocardial perfusion and diastolic function with velocity vector imaging (VVI) combined with myocardial contrast echocardiography (MCE) in dog models of coronary artery stenosis at rest and stress. Methods Different stenoses in anterior descending branch were made in 8 dogs. Before and after coronary artery stenosis, VVI evaluation was made on short axis image, then MCE were performed in the left ventricular mastoid muscle section at rest and in the peak dose of dobutamine. The myocardial blood flow A·β value and peak diastolic strain rate (SR_(dia)) on the direction of the circumference of the short view were measured, and the relationship between them was analyzed. Results At rest, no significant difference of A·β value nor SR_(dia) was found between the stenotic bed and normal bed when coronary stenosis was mild or moderate. However, A·β value and SR_(dia) of the stenotic bed were smaller than those in the normal bed when coronary stenosis was severe (P<0.05). At dobutamine stress, A·β value and SR_(dia) of the stenotic bed were already less than those in the normal bed when coronary stenosis was mild or moderate. A·β values and SR_(dia) of the stenotic bed decreased further compared to the normal bed (P<0.05) when coronary artery was severe. At both rest and stress, the standard A·β value was strongly correlated with SR_(dia) (r_(rest)=0.57,r_(stress)=0.72,P<0.01). Conclusion VVI can not only evaluate the diastolic function of myocardial segments on the short axis view, but also reflect changes of myocardial perfusion to a certain extent.