Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

Improvement of long-term risks of cardiovascular events associated with community-based disease management in Chinese patients of the Xinjiang autonomous region of China.

BACKGROUND: A recent community-based disease management (CBDM) pilot study reported a 20.5% prevalence of hypertension and a 0.5 and 3.6% prevalence of stroke and coronary heart disease (CHD), respectively, in an elderly population (mean age 65 years) in the Xin Jiang autonomous region of China. The CBDM was initiated in 2013 as an essential public health service; however, the potential long-term impact of CBDM on cardiovascular (CV: CHD and stroke) events is unknown. The objective of the study was to understand the long-term impact of CBDM interventions on CV risk factors using disease-model simulation based on a single-arm experimental study. METHODS: A discrete event simulation was developed to evaluate the impact of CBDM on the long-term CV risk among patients with hypertension, in China's Xin Jiang autonomous region. The model generated pairs of identical patients; one receives CBDM and one does not (control group). Their clinical courses were simulated based on time to CV events (CHD and strokes), which are estimated using published risk equations. The impact of CBDM was incorporated as improvement in systolic blood pressure (SBP) based on observations from the CBDM study. The simulation estimated the number of CV events over patients' lifetimes. RESULTS: During a 2-year follow up, the CBDM led to an average reduction of 8.73 mmHg in SBP from baseline, and a 42% reduction in smoking. The discrete event simulation showed that, in the control group, the model estimated incidence rates of 276, 1789, and 616 per 100,000 individuals for lifetime CHD, stroke, and CV-related death, respectively. The impact of CBDM on SBP translated into reductions of 8, 28, and 23% in CHD, stroke, and CV-related deaths, respectively. Taking into account CBDM's reduction of both SBP and smoking, deaths from CHD, stroke, and CV-related deaths were reduced by 12, 30, and 26%, respectively. CONCLUSIONS: The implementation of CBDM in China's Xinjiang autonomous region is expected to significantly reduce incidences of CHD, strokes, and CV-related deaths.

Improved immune algorithm for sudden cardiac death first aid drones site selection.

AIMS: Out-of-hospital cardiac arrest (OHCA) requires a fast emergency response, while traditional emergency takes too long to meet the demand. Combining a drone with a defibrillator can provide rapid resuscitation of OHCA patients. The aims are to improve survival in OHCA and to minimize the total system cost. METHODS: We developed an integer planning model for sudden cardiac death (SCD) first aid drone siting based on a set covering model with the stability of the siting system as the main constraint, considering the rescue time and total system cost. Using 300 points to simulate potential cardiac arrest locations in the main municipal district of Tianjin, China, the SCD first aid drone siting points are solved using an improved immune algorithm. RESULTS: Based on the actual parameters set by the SCD first aid drone, 25 siting points were solved in the main municipal district of Tianjin, China. These 25 sites were able to cover 300 simulated potential demand points. The average rescue time was 127.18 s and the maximum rescue time was 296.99 s. The total system cost was 136,824.46 Yuan. Comparing the pre- and post-algorithm solutions, the system stability was improved by 42.22%, and the maximum number of siting points corresponding to demand points was reduced by 29.41% and the minimum number was increased by 16.86%, which is closer to the average. CONCLUSIONS: We propose the SCD emergency system and use the improved immune algorithm for example solving. Comparing the solution results using the pre- and post-improvement algorithms, the cost solved by the post-improvement algorithm is less and the system is more stable.

Comparing four immunosuppressive agents for chronic spontaneous urticaria-A network meta-analysis.

BACKGROUND: Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents. OBJECTIVE: The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU. METHODS: PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects. RESULTS: This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples. CONCLUSION: Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.

Construction and application of enhanced recovery after surgery-optimized management system with nurse-led multidisciplinary cooperation.

AIM: To evaluate the effect of enhanced recovery after surgery (ERAS)-optimized management system with nurse-led multidisciplinary cooperation. DESIGN: A quasi-experimental design. METHODS: Nursing department cooperated with medical and clinical department to establish an ERAS-optimized management system. After the system was developed, it was applied in surgical departments of the hospital. Using convenience sampling, 220 selective surgical patients, 82 nurses and 98 doctors from January 1st, 2021 to July 31st, 2021 were selected as the trial group. 220 selective surgical patients, 82 nurses and 98 doctors were selected as the control group from January 1st, 2020 to July 31st, 2020. ERAS observation indicators were compared between the two groups before and 6 months after implementation. The nurse professional identity scores and satisfaction of medical cooperation scores of the two groups at different time points were analysed by repeated analysis of variance. RESULTS: After the implementation, ERAS observation indicators in the trial group were better than the control group (p < 0.05). There were significant differences in the group main effect, time main effect and interaction effect of nurse professional identity scores, satisfaction of medical cooperation scores and scores in all dimensions between the two groups (p < 0.05). The scores of the experimental group at 3 months and 6 months after implementation were better than those of the control group (p < 0.05). CONCLUSIONS: Enhanced recovery after surgery-optimized management system with nurse-led multidisciplinary cooperation was an effective working method. It could promote patients recovery and enhance nurse professional identity.

The Identification of A Novel HIV-1 Second-Generation Recombinant form (CRF01_AE/CRF07_BC) Among Men Who Have Sex with Men in Jiangsu, China.

BACKGROUND: CRF01_AE and CRF07_BC are the two major HIV-1 virus strains circulating in China. The proportion of dominant subtypes (CRF01_AE and CRF07_BC) among MSM in Jiangsu province was over 80%. A large number of URFs have been found in China in recent years. OBJECTIVE: This study aimed to report on novel HIV-1 recombinants. METHODS: We constructed Phylogenetic trees using the maximum likelihood (ML) method with 1000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination breakpoints using SimPlot 3.5.1. RESULTS: We identified a novel, second-generation HIV-1 recombinant (JS020202) between CRF01_ AE and CRF07_BC. The analysis of near full-length genome (NFLG) showed there were at least 8 breakpoints in the virus, which differed from any previously identified CRF and URF around the world. CONCLUSION: Novel diverse CRF01_AE/07_BC suggested the complexity trends of HIV-1 genetics. The emergency situation of diverse recombinant strains should be monitored continuously.

Human neutralising antibodies elicited by SARS-CoV-2 non-D614G variants offer cross-protection against the SARS-CoV-2 D614G variant.

OBJECTIVES: The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralise against the G614 variant. METHODS: Antibody profiling against the SARS-CoV-2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS-CoV-2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID-19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). RESULTS: Profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. CONCLUSIONS: Cross-reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS-CoV-2. More importantly, there should be negligible impact towards the efficacy of antibody-based therapies and vaccines that are currently being developed.

Predictive value of post-operative drain amylase levels for post-operative pancreatic fistula.

BACKGROUNDS/AIMS: Traditionally, surgically placed pancreatic drains are removed, at the discretion of the operating surgeon. Moving towards enhanced recovery after surgery (ERAS), we looked for predictors for early drain removal. The purpose of this paper was to establish which postoperative days' (POD) drain amylase is most predictive against post-operative pancreatic fistula (POPF). METHODS: We conducted a retrospective study of 196 patients who underwent pancreatic resection at our institute from January 2006 to October 2013. Drain amylase levels were routinely measured. The International Study Group of Pancreatic Fistula (ISGPF) definition of POPF, and clinical severity grading were used. RESULTS: 5.1% (10 of 196) patients developed ISGPF Grades B and C POPF. Negative predictive value of developing significant POPF, if drain amylase values were low on PODs 1 and 3 was 98.7% (95% CI: 0.93-1.00). This translated to confidence in removing surgically placed pancreatic drains, at POD 1 and 3 when drain amylase values are low. CONCLUSIONS: Patients with low drain amylase values on POD 1 and 3, are unlikely to develop POPF and may have pancreatic drains removed earlier.

Validity of the Barcelona Clinic Liver Cancer and Hong Kong Liver Cancer staging systems for hepatocellular carcinoma in Singapore.

BACKGROUND: Staging is vital in guiding therapeutic approach in patients diagnosed with hepatocellular carcinoma (HCC). Our study's goal is to compare paradigms in the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) systems, and evaluate the use of both in a local context, comparing their prognostic ability and therapeutic efficacy in the management of HCC. METHODS: Seven hundred and sixty-six patients diagnosed between 2010 and 2015 were identified and staged according to BCLC and HKLC. Both system's performances were compared using Akaike information criterion (AIC), bootstrap concordance-index (c-index), and through Kaplan-Meier survival curves of patients who came under HKLC stages 1, 2, and 3 and the individual BCLC stages. Independent prognostic factors of survival were identified using univariate and multivariate analyses. RESULTS: According to AIC and c-index, HKLC (AIC = 5,711, c-index = 0.74) has equivalent prognosticating value as BCLC (AIC = 5,764, c-index = 0.72). Through Kaplan-Meier curves, we determined that more aggressive treatments resulted in better outcomes. Particularly for patients under BCLC stage C, patients who followed the HKLC system's recommended treatments performed markedly better. CONCLUSIONS: In our patient population, the HKLC system is comparable to the BCLC system in prognosticating patients, but is suggested to have better performance in guiding treatment.

Supercapacitor electrode with a homogeneously Co3O4-coated multiwalled carbon nanotube for a high capacitance.

Cobalt oxide (Co3O4) was homogeneously coated on multiwalled carbon nanotube through a simple chemical deposition method and employed in supercapacitor electrodes. SEM image indicated the uniform distribution of Co3O4 nanoparticles on the surface of the multiwalled carbon nanotube. A maximum specific capacitance of 273 Fg(-1) was obtained at the charge-discharge current density of 0.5 Ag(-1). After 500 cycles of continuous charge-discharge process, about 88% of the initial capacity could be retained.

Control of mu opioid receptor expression by modification of cDNA 5'- and 3'-noncoding regions.

Removal of a 712 base pair (bp) sequence following the coding region of a human micro opioid receptor (hmuOR) cDNA unexpectedly increased expression of the receptor protein. A series of 3'-noncoding region deletion mutants revealed that at least three discrete regions following the stop codon influenced receptor expression levels. Deletion of the 205-bp 5'-noncoding region immediately preceding the Kozak sequence doubled receptor expression relative to wild type, and simultaneous deletion of 5'- and 3'-noncoding regions increased expression several fold. The hmuOR noncoding regions may participate in a regulatory mechanism that controls the number of cell surface receptors.

Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.