Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

叔丁醇治疗SD大鼠硒性白内障的疗效观察

目的:探讨叔丁醇外用滴眼液对SD大鼠硒性白内障模型(模拟老年性白内障)的治疗作用. 方法:建立SD大鼠硒性白内障模型,并将实验大鼠右眼作为药物干预组,左眼作为对照组;用自行配制的叔丁醇外用滴眼液(浓度分别为25、50、75 mmol/L)按时滴眼(1滴/次,3~5次/d);每日进行肉眼观察,并于用药后第5日及第10日用裂隙灯显微镜观察大鼠双眼晶状体核性病变,每日用游标卡尺(最小刻度值0.02 mm)测量大鼠双眼晶状体核性斑块最大直径的改变.另选未建模的SD大鼠,用100 mmol/L的叔丁醇滴眼液滴眼(1滴/次,3~5次/d),观察药物有无毒性及其他不良反应. 结果:硒性白内障大鼠用药眼晶状体核性混浊斑块直径小于对照眼(P<0.01);用药眼核性混浊斑块混浊程度低于对照眼;叔丁醇滴眼液毒性低,刺激性小. 结论:叔丁醇滴眼液对SD大鼠硒性白内障有一定的治疗作用.     

Diagnostic significance of long non-coding RNAs expression in tuberculosis patients: A systematic review and meta-analysis

Objectives:It is crucial to identify effective diagnostic biosignatures of tuberculosis (TB) to optimize its treatment. Herein, we conducted a systematic review to elucidate the diagnostic efficacy of long noncoding RNA (lncRNAs) as TB biomarkers.Methods:We searched Medline, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biology Medicine disc databases up to February 18, 2020. These studies focusing on lncRNAs as diagnosis markers of TB were collected. STATA 12.0 and Meta-disc1.4 software were used to analyze the data extracted from eligible studies.Results:We included 8 articles with 1058 TB patients, and 1896 healthy controls in our study. The values of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.63, 0.86, 4.48, 0.43, and 10.31, respectively. Additionally, we plotted the summary receiver operating characteristic curve to evaluate the diagnostic accuracy, and the area under the curve was 0.80.Conclusion:The present study is the first meta-analysis to assess the diagnostic accuracy of lncRNAs in TB patients. We found that lncRNAs might constitute potential biomarkers for the diagnosis of TB patients. More population-based high-quality research should be conducted to validate the efficacy lncRNAs in TB patients.     

Experimental evidence of physician social preferences

Physicians’ professional ethics require that they put patients’ interests ahead of their own and that they should allocate limited medical resources efficiently. Understanding physicians’ extent of adherence to these principles requires understanding the social preferences that lie behind them. These social preferences may be divided into two qualitatively different trade-offs: the trade-off between self and other (altruism) and the trade-off between reducing differences in payoffs (equality) and increasing total payoffs (efficiency). We experimentally measure social preferences among a nationwide sample of practicing physicians in the United States. Our design allows us to distinguish empirically between altruism and equality–efficiency orientation and to accurately measure both trade-offs at the level of the individual subject. We further compare the experimentally measured social preferences of physicians with those of a representative sample of Americans, an “elite” subsample of Americans, and a nationwide sample of medical students. We find that physicians’ altruism stands out. Although most physicians place a greater weight on self than on other, the share of physicians who place a greater weight on other than on self is twice as large as for all other samples—32% as compared with 15 to 17%. Subjects in the general population are the closest to physicians in terms of altruism. The higher altruism among physicians compared with the other samples cannot be explained by income or age differences. By contrast, physicians’ preferences regarding equality–efficiency orientation are not meaningfully different from those of the general sample and elite subsample and are less efficiency oriented than medical students.

In a classic article, Kenneth Arrow (1) argued that asymmetric information pervades the health-care market. Patients rely on physicians’ expert knowledge in planning their medical care. Health insurers and government agencies (Medicare and Medicaid) largely rely on physicians to decide which treatments are appropriate for their patients. This deference to physicians’ authority may be justified given their superior expertise and informational advantages (2). However, the dual role of recommending and providing treatments creates opportunities for physicians to place their interests ahead of their patients’ interests, for example by recommending profitable tests and treatments that offer little or no health benefits. A second risk is more subtle. Physicians must trade off their individual patients’ interests in getting care, even if the benefit is likely to be small, against society’s interest in allocating limited medical resources efficiently, in order to generate the greatest benefits for the overall health of a population.The norms of physician professionalism—including, in particular, the patient-centered norms that constitute physicians’ traditional professional ethic—are intended to address the risk of selfishness. Arrow argues that due to information asymmetry, the principle of“buyer beware” that governs ordinary consumer markets should be replaced, in health care, by the physicians’ professional responsibility to put patients’ interests ahead of their own (1). Physician leaders publicly promote the importance of professionalism, while exhorting physicians to act altruistically. For example, the editors of the New England Journal of Medicine have asserted that “medicine is one of the few spheres of human activity in which the purposes are unambiguously altruistic” (3), while the American Board of Internal Medicine similarly asserts that “altruism is the essence of professionalism … the best interest of patients, not self-interest, is the rule” (4). On the other hand, empirical studies have suggested that, at least in some situations, some physicians create “supplier-induced demand,” which influences a patient’s demand for care “against the physician’s interpretation of the best interest of the patient” (5), contributing to skepticism about whether physicians do in fact behave altruistically. [Such skepticism is not limited to medicine. Legal ethics, for example, has long sought to control lawyers’ abuse of discretion through professional norms of client loyalty and care (6). But skeptics have cast these norms as self-serving, and the law governing lawyers increasingly subjects them to elaborate institutionalized mechanisms of bureaucratic control.]While the effects of professional norms on physician behavior are difficult to measure directly, a clearer understanding of physicians’ social preferences can help to illuminate whether professional norms and physicians’ individual preferences are oppositional or aligned. Our study therefore helps to evaluate the likely effectiveness of both professional norms and the turn to bureaucracy. While altruism and related professional norms are important in many other professions (7), the distinct characteristics of the market for medical care, namely information asymmetry and uncertainty in the relationship between medical treatments and patient outcomes (1), render it especially critical to study these issues among physicians.Health care systems in the US and elsewhere address the second risk—concerning efficiency—in more complex ways. Although professional ethics give physicians a responsibility to conserve scarce medical resources (8), the norm that directs individual physicians to put their patients first may render a norm-based approach inadequate to the problem of efficiency (9). Health insurers therefore use bureaucratic mechanisms and financial incentives to manage the information asymmetry between a physician who knows the specific patient’s situation and the insurer which does not (9).^*We deploy an incentivized economic experiment to investigate both altruism (the trade-off between self and other) and equality–efficiency orientation (the trade-off between reducing self–other differences in payouts and increasing payout totals) in practicing US physicians, and we compare our results with analogous experiments that measure parallel behaviors in other populations. A vast literature considers social preferences, and laboratory experiments have been very fruitful in both establishing the empirical reliability of such preferences and directing theoretical attention to them. [We will not attempt to review the enormous body of work in behavioral and experimental economics on social preferences. Camerer (10) provides a comprehensive discussion, if now somewhat dated, of the vast body of experimental and theoretical research in economics focusing on dictator, ultimatum, and trust games. Engel (11) provides the most comprehensive meta-study of dictator games.] After presenting our results, we relate them to the results from prior work that are particularly relevant to our study (Discussion). We note that the social preferences of physicians and professionals more generally remain relatively understudied, and our discussion of the relationship between our study and prior work explains the specific contributions that we make.Our sample consists of 284 physicians from 36 medical groups around the United States, including physicians in primary care (internal medicine and family medicine) and cardiology, and physicians in private practices and employed by hospitals. Our experiment gives subjects broad discretion to implement their preferences, free from bureaucratic control or even surveillance. Our results therefore inform the question whether norms are likely to affect physician choices along both dimensions of behavior. Our study measures altruism in a large multisite sample of practicing physicians and measures both dimensions of social preferences.Our experiment asked subjects to make trade-offs between their own self-interest and the interest of an anonymous other and, at the same time, between equality and efficiency. These two aspects of social preferences often operate together, but they remain conceptually distinct. [Social preferences can be weighted toward equality (reducing differences in payoffs) or weighted toward efficiency (increasing total payoffs) and range from pure utilitarian to maxmin or Rawlsianism. As the dispute between Harsanyi (12, 13) and Rawls (14) shows, fair-minded people (who are all perfectly impartial between self and other) can disagree about how to trade off equality and efficiency. The work of Harsanyi and Rawls, and of the many others who have followed them, has had broad-reaching influence across many disciplines, including philosophy, economics, and law.] To capture both of these features in our experiment, we employ a modified dictator game (15–17) in which we ask physicians to allocate real money between themselves and an anonymous other drawn from a broadly representative sample of the US population. Our experiment presents subjects with allocation decisions in which the “price of giving” varies across decision problems—sometimes the subject may need to sacrifice more than a token (the experimental currency)—to give a single token to other (the recipient); in other decisions, it may cost only a fraction of a token. These decisions are made through an intuitive “point-and-click” graphical interface in which the choices are represented as a budget line where each point represents a possible allocation. The slope of the line captures the price of giving tokens to other.^†Intuitively, this method allowed us to collect a rich dataset capable of measuring both altruism and equality–efficiency orientation at the level of the individual subject. [The importance of studying individual heterogeneity in social preferences is emphasized by Andreoni and Miller (17). Because of this heterogeneity, it is necessary to investigate behavior at an individual level. Our experimental design allows subjects to make numerous choices over a wide range of budget lines, and this yields a rich dataset that is well-suited to analysis at the individual level. It is clearly advantageous to estimate individual-level parameters and then generate individual-level distributions of the estimations rather than to pool data and then estimate population-level parameters.] The degree of altruism is reflected in the amount subjects give on average, whereas equality–efficiency orientation is captured by how subjects respond to the price of giving. Increasing the fraction of the budget spent on other as the price of giving increases indicates social preferences weighted toward equality (reducing the difference in payoffs between self and other), whereas decreasing it when the price of giving increases indicates social preferences weighted toward efficiency (increasing the total payoffs to self and other). We rely on techniques developed in our prior work (15, 16, 18) to evaluate the consistency of physicians’ choices (i.e., whether they reflect a complete and transitive preference ordering) and to explore the structure of the social utility functions that rationalize the observed data.We further compare physicians’ preferences with preferences previously measured in three other populations using equivalent experiments: 1) a broadly representative sample of US adults (18), 2) an “elite” subsample of those who hold a graduate degree and have an annual household income over $100,000 (15, 18), and 3) a sample of medical students from nine schools around the United States (19, 20). The social preferences of these populations provide important benchmarks against which physicians’ social preferences can be assessed; furthermore, the comparison with medical students may shed light on whether physicians’ distinctive social preferences reflect a “selection effect” based on who enters medicine or a “treatment effect” of practicing medicine.^‡We begin our analysis of the experimental data by using classical revealed preference theory (21–23) to test whether subjects’ choices are consistent with the essence of all traditional models of economic decision-making—utility maximization.^§ Our physician subjects exhibit a remarkably high degree of consistency when compared with other populations, including medical students and also students from Yale Law School (YLS), the population that had exhibited the highest degree of consistency in prior experiments (15). [In our subsequent analysis, we do not draw detailed comparisons between our physician sample and the sample YLS students (15). The experimental design in Fisman et al. (15) differs from the current one in that the YLS student subjects were asked to allocate money between themselves and another student, rather than an individual drawn from a sample broadly representative of the US adults.] This result reveals that our physician subjects are highly adept at implementing a consistent, well-behaved social preference ordering. This makes it natural to estimate—at the level of the individual subject—the substantive social preferences that physicians display.We then estimate social preferences at the level of the individual physician using a constant elasticity of substitution (CES) utility function commonly employed by economists in demand analysis. The CES functional form is appealing because the degree of altruism and equality–efficiency orientation are each independently represented in a precise and transparent manner through its two parameters, which we estimate separately for each subject (further details on the CES specification and estimation are provided in Empirical Framework).We find that physicians are more altruistic than any other population, while physicians’ preferences concerning the trade-off between equality and efficiency are almost indistinguishable graphically from the preferences of the American Life Panel (ALP) elites and also the broader ALP sample. These findings on physicians’ distinctive social preferences have direct and concrete implications for professionalism, incentives, and bureaucratic rules directed at physicians. Insofar as physicians are altruistic, they may be more likely to live up to the professional ideal of putting patients’ interests ahead of their own. At the same time, altruism as captured in our experiment is far from ubiquitous, even among physicians and, furthermore, physicians’ efficiency orientation is indistinguishable from than that of the general population. Taken together, our findings suggest that the ideal of physician professionalism—putting the patient first—is not merely a self-serving myth but that other mechanisms may be required to support the quality of medical care and to promote efficient allocation of medical resources.     

基于技术接受模型的新建医院信息系统护士使用满意度影响因素研究

介绍技术接受模型特点及应用情况,基于技术接受模型并应用问卷调查方法,分析新建医院护士使用医院信息系统满意度现状及影响因素,提出护理管理者应根据护士不同特征,采取针对性措施提高护士使用医院信息系统满意度。     

点阵CO2激光治疗女性轻中度压力性尿失禁的临床疗效分析

目的探究经阴道点阵CO₂激光治疗女性轻、中度压力性尿失禁(SUI)的临床疗效。方法回顾性研究本院2017年1月至2020年12月收治的轻中度SUI女性患者。激光治疗组41例,进行点阵CO₂激光联合盆底肌训练治疗,每月治疗1次,共治疗3次;生物反馈治疗组20例,采用生物反馈电刺激联合盆底肌训练。比较两组患者治疗后临床疗效、国际尿失禁委员会尿失禁问卷简表(ICI-Q-SF)、尿失禁生活质量问卷(I-QOL)及女性性功能量表(FSFI)评分。结果治疗后,激光治疗组总有效率为92.68%,疗效强于生物反馈组(P<0.05);治疗后ICI-Q-SF、I-QOL、FSFI评分均得到改善(P<0.01);与生物反馈治疗组比较,激光治疗组I-QOL、FSFI增加更显著(P<0.05),ICI-Q-SF评分明显降低(P<0.01)。3例患者治疗时述阴道烧灼感,休息后好转,5例患者出现一过性的尿急,部分患者阴道分泌物增多后自行恢复,整个治疗过程无其他不良事件发生。结论点阵CO₂激光治疗能够有效改善轻、中度SUI患者的...     

MRI基本征象结合DWI参数鉴别非典型脑膜瘤和间变型脑膜瘤

目的 通过MRI基本征象结合扩散加权成像(diffusion-weighted imaging,DWI)参数鉴别非典型脑膜瘤(atypical meningioma,AM)和间变型脑膜瘤(anaplastic meningioma,AAM),提高术前诊断准确度.材料与方法 回顾性分析经病理证实的44例AM患者和16例A...     

An integrated strategy for the comprehensive profiling of the chemical constituents of Aspongopus chinensis using UPLC-QTOF-MS combined with molecular networking

ContextThe extracts of Aspongopus chinensis Dallas (Pentatomidae), an insect used in traditional Chinese medicine, have a complex chemical composition and possess multiple pharmacological activities.ObjectiveThis study comprehensively characterizes the chemical constituents of A. chinensis by an integrated targeted and untargeted strategy using UPLC-QTOF-MS combined with molecular networking.Materials and methodsThe ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with molecular networking-based dereplication was proposed to facilitate the identification of the chemical constituents of aqueous and ethanol extracts of A. chinensis. The overall strategy was designed to avoid the inefficiency and costliness of traditional techniques. The targeted compounds discovered in the A. chinensis extracts were identified by searching a self-built database, including fragment ions, precursor ion mass, and other structural information. The untargeted compounds were identified by analyzing the relationship between different categories, fragmentation pathways, mass spectrometry data, and the structure of the same cluster of nodes within the molecular network. The untargeted strategy was verified using commercial standard samples under the same mass spectrometry conditions.ResultsThe proposed integrated targeted and untargeted strategy was successfully applied to the comprehensive profiling of the chemical constituents of aqueous and ethanol extracts of A. chinensis. A total of 124 compounds such as fatty acids, nucleosides, amino acids, and peptides, including 74 compounds that were reported for the first time, were identified in this study.ConclusionsThe integrated strategy using LC tandem HRMS combined with molecular networking could be popularised for the comprehensive profiling of chemical constituents of other traditional insect medicines.     

抢救车分级管理方案的应用效果

目的 探讨抢救车分级管理方案的应用效果。方法 回顾性分析2018年1月至12月萍乡矿业集团有限责任公司总医院和萍乡市第二人民医院分级管理实施前71辆抢救车的使用情况,据此制订抢救车分级管理方案,并于2020年1月至12月正式投入临床应用,比较分级管理方案实施前后抢救车过期药品的损耗数量、损耗金额、抢救车管理工作总耗时及医护人员对管理方案的满意度。结果 分级管理方案实施后,抢救车药品过期数量及损耗金额均低于实施前,差异有统计学意义（P<0.05）;抢救车科室质控次数、护理部质控次数和科室护理人员质控耗时均低于实施前,差异有统计学意义（P<0.05）;共有71名医护人员参与本研究方案的满意度评价工作,分级管理方案实施后,医护人员的总满意度高于实施前,差异有统计学意义（P<0.05）。结论 抢救车分级管理方法具有临床应用价值,该方案能够减少药品损耗、提高质控工作效率,医护人员对该方案满意度较高。     

A Comparison of Pseudorabies Virus Latency to Other α-Herpesvirinae Subfamily Members

Pseudorabies virus (PRV), the causative agent of Aujeszky’s disease, is one of the most important infectious pathogens threatening the global pig industry. Like other members of alphaherpesviruses, PRV establishes a lifelong latent infection and occasionally reactivates from latency after stress stimulus in infected pigs. Latent infected pigs can then serve as the source of recurrent infection, which is one of the difficulties for PRV eradication. Virus latency refers to the retention of viral complete genomes without production of infectious progeny virus; however, following stress stimulus, the virus can be reactivated into lytic infection, which is known as the latency-reactivation cycle. Recently, several research have indicated that alphaherpesvirus latency and reactivation is regulated by a complex interplay between virus, neurons, and the immune system. However, with those limited reports, the relevant advances in PRV latency are lagging behind. Therefore, in this review we focus on the regulatory mechanisms in PRV latency via summarizing the progress of PRV itself and that of other alphaherpesviruses, which will improve our understanding in the underlying mechanism of PRV latency and help design novel therapeutic strategies to control PRV latency.