CD44基因多态性与宫颈癌及非小细胞肺癌的相关性

背景与目的：CD44分子是众多肿瘤细胞的标志分子，其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性（single nucleotide polymorphism，SNP）位点与云南汉族人群宫颈癌和非小细胞肺癌（nonsmall cell lung cancer，NSCLC）易感性的相关性。方法：选取了CD44基因中的两个SNP位点rs13347和rs8193，采用TagMan基因分型的方法，分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征，并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果：rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义（P>0.05）。而在NSCLC组和对照组的比较中：rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义（P=0.020和P=0.004）；这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义（P=0.027和P=0.020）；其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组，可能是NSCLC发生的风险因素（OR=1.250，95% CI：1.035～1.509），rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组，可能是NSCLC发生的保护性因素（OR=0.768，95%CI：0.641～0.921）。单倍型分析结果显示，rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义（P=0.003和0.022）；该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素（OR=1.316，95%CI：1.096～1.579）。结论：CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关，而可能与云南汉族人群NSCLC具有相关性。     

The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially V_H4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of V_H4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs.     

Intervention for arch obstruction after the Norwood procedure: Prevalence,associated factors,and practice variability

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.

Anatomic vs. reverse shoulder arthroplasty for glenohumeral osteoarthritis with intact rotator cuff: a retrospective comparison of patient-reported outcomes using the systems outcomes database with up to 5-year follow-up

BackgroundThe growing enthusiasm for the use of reverse shoulder arthroplasty (RSA) in the treatment of primary glenohumeral osteoarthritis (GHOA) with an intact rotator cuff is based on data derived from single-center studies with limited generalizability and follow-up. This study compared patient-reported outcomes (PROs) between RSA and total shoulder arthroplasty (TSA) for the treatment of primary GHOA with up to 5-year follow-up and examined temporal trends in the treatment of GHOA between 2012 and 2021.MethodsA retrospective review was performed on patients with primary GHOA undergoing primary arthroplasty surgery from the Surgical Outcomes System global registry between 2012 and 2021. PROs including the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, and visual analog scale (VAS) for pain were compared between RSA and TSA at 1, 2, and 5 years postoperatively.ResultsA total of 4451 patients were included, with 2693 (60.5%) undergoing TSA and 1758 (39.5%) undergoing RSA. Both RSA and TSA provided clinically excellent outcomes at 1 year postoperatively (ASES: 80.8 ± 17.9 vs. 85.9 ± 15.2, respectively; SANE: 74.8 ± 24.7 vs. 79.5 ± 22.9; VAS pain: 1.3 ± 2.0 vs. 1.1 ± 1.7; all P < .05) that were maintained at 2 years (ASES: 81.3 ± 19.3 vs. 87.3 ± 14.9; SANE: 74.8 ± 26.2 vs. 79.7 ± 24.7; VAS pain: 1.3 ± 2.1 vs. 1.0 ± 1.6; all P < .05) and 5 years (ASES: 81.7 ± 16.5 vs. 86.9 ± 15.3; SANE: 71.6 ± 28.5 vs. 78.2 ± 25.9; VAS pain: 1.0 ± 1.7 vs. 1.0 ± 1.7; all P < .05), with statistical significance favoring TSA. After controlling for age and sex, there was an adjusted difference of 4.5 units in the ASES score favoring TSA (P = .005) at 5 years postoperatively but no differences in adjusted SANE (P = .745) and VAS pain (P = .332) scores. The use of RSA for GHOA grew considerably over time, from representing only 17% of all replacements performed for GHOA in 2012 to nearly half (47%) in 2021 (P < .001).ConclusionRSA as a treatment for GHOA with an intact rotator cuff seems to yield PROs that are largely clinically equivalent to TSA extending to 5 years postoperatively. The observed statistical significance favoring TSA appears to be of marginal clinical benefit based on established minimal clinically important differences and may be a result of the large sample size. Further research using more granular clinical data and examining differences in range of motion and complications is warranted as it may change the value analysis.     

Principles of pressure transducer function and sources of error in clinical use

The invasive measurement of physiological pressures is a common requirement in anaesthesia and intensive care medicine. From arterial blood pressure to intracranial pressure, these calculated variables give a swift graphical and numerical representation of a patient's current physiological status. This allows us to respond rapidly to conditions outside our preferred parameters and to carefully titrate treatment to target effects. These systems are, however, not infallible. An understanding of the principles of their function will promote appropriate use and an ability to recognize and react to sources of error. This article aims to furnish the reader with this level of understanding in order to inform their academic and clinical practice.     

Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccine

BackgroundAs the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers’ and infant caregivers’ attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia.MethodsWe conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4 months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4 month immunization visit were surveyed.FindingsPrior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed.ConclusionHealthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase.     

Heteroepitaxy of Cerium Oxide Thin Films on Cu(111)

An important part of fundamental research in catalysis is based on theoretical and modeling foundations which are closely connected with studies of single-crystalline catalyst surfaces. These so-called model catalysts are often prepared in the form of epitaxial thin films, and characterized using advanced material characterization techniques. This concept provides the fundamental understanding and the knowledge base needed to tailor the design of new heterogeneous catalysts with improved catalytic properties. The present contribution is devoted to development of a model catalyst system of CeO₂ (ceria) on the Cu(111) substrate. We propose ways to experimentally characterize and control important parameters of the model catalyst—the coverage of the ceria layer, the influence of the Cu substrate, and the density of surface defects on ceria, particularly the density of step edges and the density and the ordering of the oxygen vacancies. The large spectrum of controlled parameters makes ceria on Cu(111) an interesting alternative to a more common model system ceria on Ru(0001) that has served numerous catalysis studies, mainly as a support for metal clusters.     

A review of the effectiveness of aspartame in helping with weight control

Summary Strategies to reverse the upward trend in obesity rates need to focus on both reducing energy intake and increasing energy expenditure. The provision of low‐ or reduced‐energy‐dense foods is one way of helping people to reduce their energy intake and so enable weight maintenance or weight loss to occur. The use of intense sweeteners as a substitute for sucrose potentially offers one way of helping people to reduce the energy density of their diet without any loss of palatability. This report reviews the evidence for the effect of aspartame on weight loss, weight maintenance and energy intakes in adults and addresses the question of how much energy is compensated for and whether the use of aspartame‐sweetened foods and drinks is an effective way to lose weight. All studies which examined the effect of substituting sugar with either aspartame alone or aspartame in combination with other intense sweeteners on energy intake or bodyweight were identified. Studies which were not randomised controlled trials in healthy adults and which did not measure energy intakes for at least 24 h (for those with energy intakes as an outcome measure) were excluded from the analysis. A minimum of 24‐h energy intake data was set as the cut‐off to ensure that the full extent of any compensatory effects was seen. A total of 16 studies were included in the analysis. Of these 16 studies, 15 had energy intake as an outcome measure. The studies which used soft drinks as the vehicle for aspartame used between 500 and about 2000 ml which is equivalent to about two to six cans or bottles of soft drinks every day. A significant reduction in energy intakes was seen with aspartame compared with all types of control except when aspartame was compared with non‐sucrose controls such as water. The most relevant comparisons are the parallel design studies which compare the effects of aspartame with sucrose. These had an overall effect size of 0.4 standardised difference (SD). This corresponds to a mean reduction of about 10% of energy intake. At an average energy intake of 9.3 MJ/day (average of adult men and women aged 19–50 years) this is a deficit of 0.93 MJ/day (222 kcal/day or 1560 kcal/week), which would be predicted (using an energy value for obese tissue of 7500 kcal/kg) to result in a weight loss of around 0.2 kg/week with a confidence interval 50% either side of this estimate. Information on the extent of compensation was available for 12 of the 15 studies. The weighted average of these figures was 32%. Compensation is likely to vary with a number of factors such as the size of the caloric deficit, the type of food or drink manipulated, and timescale. An estimate of the amount of compensation with soft drinks was calculated from the four studies which used soft drinks only as the vehicle. A weighted average of these figures was 15.5%. A significant reduction in weight was seen. The combined effect figure of 0.2 SD is a conservative figure as it excludes comparisons where the controls gained weight because of their high‐sucrose diet and the long‐term follow‐up data in which the aspartame groups regained less weight than the control group. An effect of 0.2 SD corresponds to about a 3% reduction in bodyweight (2.3 kg for an adult weighing 75 kg). Given the weighted average study length was 12 weeks, this gives an estimated rate of weight loss of around 0.2 kg/week for a 75‐kg adult. The meta‐analyses demonstrate that using foods and drinks sweetened with aspartame instead of sucrose results in a significant reduction in both energy intakes and bodyweight. Meta‐analyses both of energy intake and of weight loss produced an estimated rate of weight loss of about 0.2 kg/week. This close agreement between the figure calculated from reductions in energy intake and actual measures of weight loss gives confidence that this is a true effect. The two meta‐analyses used different sets of studies with widely differing designs and controls. Although this makes comparisons between them difficult, it suggests that the final figure of around 0.2 kg/week is robust and is applicable to the variety of ways aspartame‐containing foods are used by consumers. This review has shown that using foods and drinks sweetened with aspartame instead of those sweetened with sucrose is an effective way to maintain and lose weight without reducing the palatability of the diet. The decrease in energy intakes and the rate of weight loss that can reasonably be achieved is low but meaningful and, on a population basis, more than sufficient to counteract the current average rate of weight gain of around 0.007 kg/week. On an individual basis, it provides a useful adjunct to other weight loss regimes. Some compensation for the substituted energy does occur but this is only about one‐third of the energy replaced and is probably less when using soft drinks sweetened with aspartame. Nevertheless, these compensation values are derived from short‐term studies. More data are needed over the longer term to determine whether a tolerance to the effects is acquired. To achieve the average rate of weight loss seen in these studies of 0.2 kg/week will require around a 220‐kcal (0.93 MJ) deficit per day based on an energy value for obese tissue of 7500 kcal/kg. Assuming the higher rate of compensation (32%), this would require the substitution of around 330 kcal/day (1.4 MJ/day) from sucrose with aspartame (which is equivalent to around 88 g of sucrose). Using the lower estimated rate of compensation for soft drinks alone (15.5%) would require the substitution of about 260 kcal/day (1.1 MJ/day) from sucrose with aspartame. This is equivalent to 70 g of sucrose or about two cans of soft drinks every day.