Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）： the mechanism, present strategies and future perspectives of therapies

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.     

Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF‍-κB pathway

Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress syndrome (ARDS) or even death. Expression of proinflammatory interleukin-‍1β (IL-‍1β) and inducible nitric oxide synthase (iNOS) in the process of pulmonary inflammation will further exacerbate the severity of ALI. The purpose of this study was to explore the effect of Palrnatine (Pa) on lipopolysaccharide (LPS)-induced mouse ALI and its underlying mechanism. Pa, a natural product, has a wide range of pharmacological activities with the potential to protect against lung injury. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to detect the expression and translation of inflammatory genes and proteins in vitro and in vivo. Immunoprecipitation was used to detect the degree of P65 translocation into the nucleus. We also used molecular modeling to further clarify the mechanism of action. The results showed that Pa pretreatment could significantly inhibit the expression and secretion of the inflammatory cytokine IL-1β, and significantly reduce the protein level of the proinflammatory protease iNOS, in both in vivo and in vitro models induced by LPS. Further mechanism studies showed that Pa could significantly inhibit the activation of the protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway in the LPS-induced ALI mode and in LPS-induced RAW264.7 cells. Through molecular dynamics simulation, we observed that Pa was bound to the catalytic pocket of Akt and effectively inhibited the biological activity of Akt. These results indicated that Pa significantly relieves LPS-induced ALI by activating the Akt/NF-κB signaling pathway.     

Effect of Palrnatine on lipopolysaccharide-induced acute lung injury by inhibiting activation of the Akt/NF-κB pathway

Journal of Zhejiang University-SCIENCE B - Inflammation plays an important role in the development of acute lung injury (ALI). Severe pulmonary inflammation can cause acute respiratory distress...     

Is there a role of TNFR1 in acute lung injury cases associated with extracorporeal circulation?

The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.     

Lung surfactant

Lung surfactant, a lipo-protein complex, is a highly surface-active material found in the fluid lining the air-liquid interface of the alveolar surface. Surfactant plays a dual function of preventing alveolar collapse during breathing cycle and protection of the lungs from injuries and infections caused by foreign bodies and pathogens. Varying degrees of structure-function abnormalities of surfactant have been associated with obstructive lung diseases, respiratory infections, respiratory distress syndromes, interstitial lung diseases, pulmonary alveolar proteinosis, cardiopulmonary bypass surgery and smoking. For some pulmonary conditions, especially respiratory distress syndrome, surfactant therapy is on the horizon.     

急性肺损伤大鼠肺中酸敏感离子通道的表达研究

目的:探讨在急性肺损伤(ALI)中酸敏感离子通道(ASIC3)的表达变化及其与ALI的关系。方法:24只雄性SD大鼠随机分为四组,LPS2h,4h,6h和对照组;以内毒素持续静脉注射复制大鼠急性肺损伤模型,急性肺损伤后2h、4h、6h时采集标本监测动脉血气、肺湿/干比、肺组织病理、免疫组化检测ASIC3在肺内的表达情况。结果急性肺损伤后4h,6h肺泡上皮细胞内ASIC3的表达明显高于对照组(P<0.05),LPS2h组和对照组相比无明显差异;肺的湿/干比LPS2h,4h和对照组相比无显著差异(P>0.05),LPS6h组明显高于对照组(P<0.05)。结论1大鼠肺泡上皮细胞和支气管粘膜上皮有ASIC3的表达;2急性肺损伤大鼠肺泡表面的ASIC3表达增多。     

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

Objectives:Severe acute pancreatitis(SAP) can lead to acute lung injury(ALI) .The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI in rats with SAP.Methods:The thin film method was used to prepare liposomes.Sprague-Dawley rats were randomly divided into three groups.After the SAP model was established by injecting 5%(w/v) sodium taurocholate(2 ml/kg body weight) into the subcapsular space of the pancreata,normal saline was administered to the control(C) group,phosphate buffer solution(PBS) -containing liposome to the Pgroup,and clodronate-containing liposome to the Tgroup through tail veins.Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase,interleukin-6(IL-6) ,and tumor necrosis factor-α(TNF-α) .Morphological changes in the pancreata and lung were observed using hematoxylin and eosin(HE) staining,while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) .In addition,the macrophage marker cluster of differentiation 68(CD68) in lung tissue was detected with immunohistochemistry.Results:Blood levels of amylase,IL-6,and TNF-αwere significantly increased in the Pgroup compared to those in the Tgroup(P0.05) .In the Tgroup,large numbers of TUNEL-positive cells were observed,but no or few in the C and Pgroups.Gross inspection and HE staining of pancreata and lung showed dramatic tissue damage,including inflammation and necrosis in the Pgroup.Less remarkable changes were noted in the Tgroup,and the C group exhibited normal histology.The histological scores according to Kaiser's criteria were consistent with HE findings.The number of CD68-positive macrophages decreased in the Tgroup.Conclusions:Clodronate-containing liposomes have a protective effect against ALI in rats with SAP.Blockade of macrophages may represent a novel therapeutic strategy in SAP.     

Molecular hydrogen is a promising therapeutic agent for pulmonary disease

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.     

SARS研究进展

SARS是由新型冠状病毒感染引起的一种以发热、咳嗽等为主要症状 ,传染性极强、病死率高的急性呼吸道传染病 ,病人能迅速发展成急性呼吸窘迫综合症而死亡。本文对该病的病原学、流行病学、发生发展过程、临床诊断及综合防制等进行了回顾和综述。     

Effects of transitions to new child care classes on infant/toddler distress and behavior

Changes in distress and problem behaviors of 38 infants/toddlers were examined after children transitioned from familiar to new classrooms to look at effects of non-continuity of caregiver. Child's age, classroom quality, teacher sensitivity, and transitioning with a peer were examined as possible mediators. Results suggest that transitions were associated with increased distress, especially for younger children. In addition, although overall classroom quality was low, children in higher quality pre-transition classrooms showed more distress after transitioning than children in lower quality classrooms. Transitions were associated with decreased problem behaviors. Both distress and problem behaviors returned to pre-transition levels within 3 weeks. Teacher sensitivity and transitioning with a peer did not relate to distress or problem behaviors. These findings contribute evidence about immediate effects of infant/toddler transitions in child care. Future research should explore child, classroom, and teacher–child relationship variables that influence effects of continuity versus non-continuity of caregiver.     

Effective Counseling for Racial/Ethnic Minority Clients: Examining Changes Using a Practice Research Network

Studies have shown that counseling decreases students' academic distress. These findings, however, are based primarily on European American students. This study explored the impact of counseling on academic distress for treatment‐seeking racial/ethnic minority college students using the Counseling Center Assessment of Psychological Symptoms–34 ( Locke et al., 2012 ) Academic Distress subscale. Results indicated that there are significant differences in academic distress at intake based on race/ethnicity. Furthermore, findings revealed that change in academic distress over the course of treatment varies by race/ethnicity.     

Psychological distress and help seeking amongst higher education students: findings from a mixed method study of undergraduate nursing/midwifery and teacher education students in Ireland

Psychological distress as experienced by higher education students is of major concern because of its potential to adversely impact academic performance, retention, mental health and lifestyle. This paper reports a mixed method investigation of student self-reported psychological distress and help-seeking behaviour. The sample comprised all students (n?=?1557) registered on undergraduate nursing/midwifery and teacher education programmes at an Irish university. Participants (n?=?1112) completed the General Health Questionnaire (GHQ) to determine their self-reported psychological distress and the Lifestyle Behaviour Questionnaire to examine sources of distress, lifestyle and demographic variables. Individual interviews (n?=?59) explored student experiences of psychological distress and their help-seeking behaviours. Forty two percent of respondents exceeded the GHQ threshold ≥5, which signifies risk of mental or physical health problems. Sources of distress included academic, financial and psychosocial stressors. Regression analysis identified that demographic, programmatic and lifestyle variables predicted GHQ scores. Despite the distress experienced, students were reluctant users of support services. Many actively avoided seeking help. These findings raise serious concerns about the extent of psychological distress among this population. They also alert education providers to be vigilant for student psychological distress and to provide effective interventions, cognisant of the impact of stigma on help seeking.     

Tolerance begins at home: Implications for counsellor training

In recent years there has been an increasing body of literature investigating the motives of counsellors and psychotherapists. Although there are considerable methodological problems with researching this area, the consensus in this literature seems to be that one determinant for becoming a counsellor may be a conscious or unconscious wish to make good the unresolved difficulties of early childhood. The unsurprising findings that counsellors have had as least as much trauma in their early lives as the general population raise questions about the impact of this for counsellors in training. This paper summarises the literature relating to the concept of the wounded healer and examines the implications of this for tolerating distress among trainee counsellors. A model is presented that aims to address this distress and teach the trainee to practice effective preventative self-care.     

Psychological defense styles, childhood adversities and psychopathology in adulthood

OBJECTIVE: The present study explores the link between reported sexual and/or physical abuse and psychological defense styles, as well as the association of both with psychological distress in adulthood. In two patient samples that differ in psychological distress and somatization, we examine whether the adversities reported and immature defense styles are associated with psychopathological symptoms. METHOD: We examined 266 consecutive inpatients in the psychosomatic department and 109 consecutive inpatients who had been treated for low-back pain in the orthopedic department of a German university hospital. Psychological defense styles were assessed by a two-factor solution of the German modified adaptation of the Defense Mechanism Inventory (DMI), childhood adversities by a structured interview, psychological distress by the SCL-90-R, and somatization by the Screening for Somatoform Disorders (SOMS). RESULTS: Both samples demonstrated a significant link between immature defense styles and the extent of overall psychological distress as well as somatization. Reported sexual and/or physical abuse of patients in both patient samples was directly associated with somatization. CONCLUSION: Recollections of sexual and/or physical abuse in childhood and immature defense styles have an association with psychopathology in adulthood. This finding suggests that immature defense styles may act, in part, as mediators between the adversities investigated and adult psychopathology.     

The development and validation of the Attitudinal Learning Inventory (ALI): a measure of attitudinal learning and instruction

In this paper, we present the development and validation of a new measure of attitudinal learning—the Attitudinal Learning Inventory (ALI). While specific scales are available for measuring attitudes, they largely focus on established attitudes, not the impact of instruction on those attitudes. We developed the inventory with two explicit objectives: (1) to measure a broad range of attitude constructs representing a holistic view of attitudinal learning and instruction; and (2) to facilitate the measurement of attitudinal learning that can be useful for educational researchers beyond traditional metrics. The ALI was developed and validated across two samples of a total of 1009 participants with diverse demographics. The ALI comprises 15 scale items and exhibited good psychometric properties and conformed to the theoretical four-dimensional structure of attitudinal learning: cognitive, affective, behavioral, and social. The ALI was also shown to correlate with behavioral metrics of class engagement. Future uses of the new measure are discussed. Participants were taken from entirely online populations, and while demographically diverse, implementation of the scale with face-to-face instruction, in varied settings, and across different groups of learners is needed to provide additional evidence of its intended generalizability and consider possible biases.     

头孢哌酮/舒巴坦治疗呼吸系统感染175例临床观察

目的观察头孢哌酮/舒巴坦治疗呼吸系统感染的疗效及安全性。方法对2006年1月～2010年12月175例用头孢哌酮/舒巴坦治疗呼吸系统感染的情况进行回顾性研究,总结其疗效及毒副作用。结果头孢哌酮-舒巴坦的用量每日2g～4g,疗程5～18天;用药后3～6.5天体温下降,体温下降率92.0%;白细胞数升高者用药后85.4%降至正常范围,炎性X线征象52.6%消失或明显吸收好转,痰细菌培养阳性者细菌清除率为85.1%;总有效率为86.9%,无效者中有12例为严重粒细胞缺乏;有16例丙氨酸转氨酶短暂升高,余未见其它副作用。结论头孢哌酮/舒巴坦治疗呼吸系统感染安全有疗效。     

鸡传染性喉气管炎的防治

鸡传染性喉气管炎（Infectious Laryngotracheitis,ILT）是由疱疹病毒属A亚群病毒感染而引发的一种急性呼吸道传染性疾病。该病具有传染性快、死亡率高、淘汰率高等特点,给家禽育种和养殖带来了非常严重的经济损失。迄今为止,对该病的防治尚无有效的方法。借鉴广大兽医工作者丰富的临床禽病治疗经验,结合自身的实践,笔者提出了一套ILT的综合防治方案。该方案在养殖实践中取得了较好的效果。     

Relations of Inhibition and Emotion-Related Parenting to Young Children's Prosocial and Vicariously Induced Distress Behavior

Children's prosocial behavior and personal distress are likely affected by children's temperament as well as parenting quality. In this study, we examined bidirectional relations from age 30 to 42 months between children's (N = 218) prosocial or self-focused (presumably distressed) reactions to a relative stranger's distress and both supportive emotion-related maternal reactions to children's emotions and children's shyness/inhibition. When controlling for 30-month prosocial behavior and personal distress behavior, maternal supportive (emotion-focused and problem-focused) reactions were positively related to prosocial behavior and marginally negatively related to children's personal distress behaviors and shyness/inhibition at 42 months. Thirty-month personal distress behavior predicted greater shyness/inhibition at 42 months, and 30-month shyness/inhibition was negatively related to prosocial behavior at 30 months.     

Parental reactions to children's negative emotions: longitudinal relations to quality of children's social functioning

Relations between self-reported parental reactions to children's negative emotions (PNRs) and children's socially appropriate/problem behavior and negative emotionality were examined longitudinally. Evidence was consistent with the conclusion that relations between children's externalizing (but not internalizing) emotion and parental punitive reactions to children's negative emotions are bidirectional. Reports of PNRs generally were correlated with low quality of social functioning. In structural models, mother-reported problem behavior at ages 10-12 was at least marginally predicted from mother-reported problem behavior, children's regulation, and parental punitive or distress reactions. Moreover, parental distress and punitive reactions at ages 6-8 predicted reports of children's regulation at ages 8-10, and regulation predicted parental punitive reactions at ages 10-12. Father reports of problem behavior at ages 10-12 were predicted by earlier problem behavior and parental distress or punitive reactions; some of the relations between regulation and parental reactions were similar to those in the models for mother-reported problem behavior. Parental perceptions of their reactions were substantially correlated over 6 years. Some nonsupportive reactions declined in the early to mid-school years, but all increased into late childhood/early adolescence.     

RGMb/DRAGON介导的信号通路及其研究进展

排斥导向分子（repulsive guidance molecule,RGM）家族包含RGMa、RGMb和RGMc三个成员.RGMb在神经、生殖、免疫系统及肾脏、肺、肌肉等重要器官均有表达,并可通过多种途径调节胚胎发育、免疫系统活性、细胞间黏附、肿瘤发生、损伤修复等重要生理过程.RGMb主要参与RGMb-neogenin-Rho信号通路和BMP信号通路,最近发现的PD-L2-RGMb结合作用提示以RGMb为中心的细胞信号网络与功能调节极为复杂.该文将以RGMb为重点,对与其相关的信号通路、生理功能调节及研究进展加以介绍.