抑瘤素M受体对慢性自身免疫性荨麻疹发病机制的影响

本研究旨在探讨抑瘤素M受体(OSMR)在慢性自身免疫性荨麻疹(CAU)发病机制中的作用。本研究分别检测30例CAU患者及30名健康受试者的皮肤组织中OSMR、JAK和STAT3的表达,研究显示OSMR、JAK和STAT3在CAU患者皮肤组织中高表达(p<0.05)。转染OSMR-siRNA可显著降低CAU模型小鼠血清炎症因子IL-1、IL-6和IFN-γ水平,而转染JAK/STAT3信号通路激动剂Tyr705则可显著升高炎症因子水平(p<0.05)。转染OSMR-siRNA可显著降低CAU小鼠瘙痒次数、瘙痒时间和嗜酸性粒细胞计数,而转染Tyr705则可显著升高CAU小鼠瘙痒次数、瘙痒时间和嗜酸性粒细胞计数(p<0.05)。转染OSMR-siRNA促进了CAU小鼠上皮细胞的增殖能力,并抑制了细胞凋亡(p<0.05)。而转染Tyr705则抑制了CAU小鼠上皮细胞的增殖能力,并促进了细胞凋亡(p<0.05)。转染OSMR-siRNA下调了上皮细胞中OSMR、JAK和STAT3的表达,而转染Tyr705则上调了OSMR、JAK和STAT3的表达(p<0.05)。总之,本研究表明OSMR基因在CAU患者皮肤组织中高表达。OSMR基因沉默可通过抑制JAK/STAT3信号通路来抑制炎症因子表达及嗜酸性粒细胞数量,促进上皮细胞增殖并抑制细胞凋亡。     

The ecology of chronic wasting disease in wildlife

Prions are misfolded infectious proteins responsible for a group of fatal neurodegenerative diseases termed transmissible spongiform encephalopathy or prion diseases. Chronic Wasting Disease (CWD) is the prion disease with the highest spillover potential, affecting at least seven Cervidae (deer) species. The zoonotic potential of CWD is inconclusive and cannot be ruled out. A risk of infection for other domestic and wildlife species is also plausible. Here, we review the current status of the knowledge with respect to CWD ecology in wildlife. Our current understanding of the geographic distribution of CWD lacks spatial and temporal detail, does not consider the biogeography of infectious diseases, and is largely biased by sampling based on hunters' cooperation and funding available for each region. Limitations of the methods used for data collection suggest that the extent and prevalence of CWD in wildlife is underestimated. If the zoonotic potential of CWD is confirmed in the short term, as suggested by recent results obtained in experimental animal models, there will be limited accurate epidemiological data to inform public health. Research gaps in CWD prion ecology include the need to identify specific biological characteristics of potential CWD reservoir species that better explain susceptibility to spillover, landscape and climate configurations that are suitable for CWD transmission, and the magnitude of sampling bias in our current understanding of CWD distribution and risk. Addressing these research gaps will help anticipate novel areas and species where CWD spillover is expected, which will inform control strategies. From an ecological perspective, control strategies could include assessing restoration of natural predators of CWD reservoirs, ultrasensitive CWD detection in biotic and abiotic reservoirs, and deer density and landscape modification to reduce CWD spread and prevalence.     

Reliability of surface electromyography for the gluteus medius muscle during gait in people with and without chronic nonspecific low back pain

The purpose of this study was to determine the intratester reliability of surface electromyography (EMG) assessment of the gluteus medius muscle in healthy people and people with chronic nonspecific low back pain (CNLBP) during barefoot walking. Gluteus medius muscle activity was measured twice in 40 people without and 30 people with CNLBP approximately 7 days apart. Walking gluteus medius muscle activity was normalised to maximal voluntary isometric contractions during side-lying hip abduction with manual resistance. Good intratester reliability (ICC > 0.75) was found for mean, peak, and peak to peak amplitude for healthy people. Only mean amplitude demonstrated good intratester reliability in those with CNLBP. Peak amplitude and peak to peak amplitude of the gluteus medius muscle of those with CNLBP, and the time of peak amplitude in both groups, demonstrated moderate reliability (ICC ranged from 0.50 to 0.58). Moderate to large standard error of measurement and minimal detectable change values were reported for outcome measurements. These results suggest that potentially large levels of random error can occur between sessions. Future research can build on this study for those with pathology and attempt to establish change values for EMG that are clinically meaningful.     

HIF‐1α forms regulatory loop with YAP to coordinate hypoxia‐induced adriamycin resistance in acute myeloid leukemia cells

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl₂ can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML.     

Mechanism of salidroside relieving the acute hypoxia-induced myocardial injury through the PI3K/Akt pathway

ObjectiveThe objective was to investigate the anti-inflammatory effects of salidroside through the PI3K/Akt signaling pathway and its protective effects on acute hypoxia-induced myocardial injury in rats.MethodsA total of 24 healthy Sprague-Dawley male rats were selected as the experimental subjects. All rats were divided into 4 groups by using the random number table method, with 6 rats in each group. The groups included the normal control group, the salidroside group, the hypobaric hypoxia group, and the hypobaric hypoxia + salidroside group. Rats in the salidroside group were fed in the original animal laboratory and were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg. Rats in the normal control group were intragastrically administered with an equal dosage of saline. Rats in the hypobaric hypoxia + salidroside group were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg, who were fed in the hypoxic experiment module for animals. The altitude was increased to 4000 m, and the rats were kept in the module for 24 h. Rats in the hypobaric hypoxia group were intragastrically administered with an equal dosage of saline in the same environment, and the altitude was increased to 4000 m after administration. Parameters of blood gas analysis, histopathological changes in cardiac tissues, cardiac indexes, and inflammatory factors IL-6 and TNF-α levels of rats in groups were compared.Results1. The cardiac indexes of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were statistically significant (P < 0.05). 2. The results of blood gas analysis of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were significantly different (P < 0.05). 3. In the hypobaric hypoxia group, the myocardial cells of rats were arranged disorderly and shaped differently, with cases such as edema, degeneration, necrosis, nucleus pyknosis, and massive infiltration of inflammatory cells. In the hypobaric hypoxia + salidroside group, the above-mentioned pathological changes in myocardial cells were relieved. 4. Compared with the hypobaric hypoxia group, in the hypobaric hypoxia + salidroside group, the concentrations of IL-6 and TNF-α in rats decreased apparently, and the differences were statistically significant (P < 0.05).ConclusionSalidroside had the repairing and protective effects on the hypobaric hypoxia-induced myocardial injuries in rats. The application of salidroside could reduce the inflammatory responses of rats with hypobaric hypoxia-induced myocardial injuries through PI3K/Akt signaling pathway, thereby protecting the myocardial cells.     

Defining CO2 and O2 syndromes of marine biomes in the Anthropocene

Research efforts have intensified to foresee the prospects for marine biomes under climate change and anthropogenic drivers over varying temporal and spatial scales. Parallel with these efforts is the utilization of terminology, such as ‘ocean acidification’ (OA) and ‘ocean deoxygenation’ (OD), that can foster rapid comprehension of complex processes driving carbon dioxide (CO₂) and oxygen (O₂) concentrations in the global ocean and thus, are now widely used in discussions within and beyond academia. However, common usage of the terms ‘acidification’ and ‘deoxygenation’ alone are subjective and, without adequate contextualization, have the potential to mislead inferences over drivers that may ultimately shape the future state of marine ecosystems. Here we clarify the usage of the terms OA and OD as global, climate change‐driven processes and discuss the various attributes of elevated CO₂ and reduced O₂ syndromes common to coastal ecosystems. We support the use of the existing terms ‘coastal acidification’ and ‘coastal deoxygenation’ because they help differentiate the sometimes rapid and extreme nature of CO₂ and O₂ syndromes in coastal ecosystems from the global, climate change‐driven processes of OA and OD. Given the complexity and breadth of the processes involved in altering CO₂ and O₂ concentrations across marine ecosystems, we provide a workflow to enable contextualization and clarification of the usage of existing terms and highlight the close link between these two gases across spatial and temporal scales in the ocean. These distinctions are crucial to guide effective communication of research within the scientific community and guide policymakers responsible for intervening on the drivers to secure desirable future ocean states.     

蚓激酶在慢性乙型肝炎治疗中的潜在作用

纤连蛋白(FN)是参与乙型肝炎病毒感染和肝脏纤维化的重要分子。 蚓激酶(LK)是从赤子爱胜蚓(Eisenia foetide)中提取的一组蛋白水解同工酶,能水解纤维蛋白治疗凝血相关疾病。 从这组同工酶中分离纯化出单一活性成分,在体外可降解纤连蛋白,被命名为蚯蚓纤连蛋白水解酶(EFNase)。 然而,LK 能否预防乙型肝炎病毒感染以及缓解因乙型肝炎导致的肝脏损伤等问题还不清楚。本研究以人肝癌细胞系HepG2.2.15为细胞模型,观察LK 对乙型肝炎表面抗原(HBsAg)或 FN 水平的影响;以 C57BL / 6J-HBV 转基因小鼠为动物模型,探讨 LK 对小鼠血清中 HBsAg、FN、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平及肝脏病理改变的影响。结果表明,LK 在体内外均能抑制HBsAg 的生成,降低血清和肝脏FN。与生理盐水处理组相比,LK 改善了肝脏的状态。这些数据为理解LK 作为治疗乙型肝炎的潜在有效药物的治疗作用提供了有价值的信息。     

幽门螺杆菌根除治疗对慢性胃炎患者肠道菌群的影响及其与血清hsCRP水平的相关性

目的探究幽门螺杆菌(H.pylori)根除治疗对慢性胃炎患者肠道菌群的影响及其与血清超敏C反应蛋白(hsCRP)水平的相关性。方法选择2018年5月至2019年5月我院收治的87例慢性胃炎患者为研究对象,所有患者均采用枸橼酸铋钾胶囊+雷贝拉唑钠肠溶胶囊+克拉霉素片+阿莫西林克拉维酸钾片进行幽门螺杆菌根除治疗,评价所有患者治疗后临床疗效、H.pylori根除率,比较所有患者治疗前后临床症状积分,肠道肠球菌、葡萄球菌、肠杆菌、乳杆菌、双歧杆菌数量及血清hsCRP水平,采用Pearson相关分析所有患者治疗后肠道菌群数量与血清hsCRP水平的相关性。结果入选患者临床治疗有效率为95.40%,H.pylori根除率为90.80%。患者治疗后腹胀、嗳气、腹痛、纳差评分显著低于治疗前(均P<0.05)。治疗后患者肠道肠球菌、葡萄球菌数量显著高于治疗前,而肠杆菌、乳杆菌、双歧杆菌数量显著低于治疗前(均P<0.05)。患者治疗后血清hsCRP水平显著低于治疗前(P<0.05)。患者治疗后肠道肠球菌、葡萄球菌、乳杆菌、肠杆菌、双歧杆菌数量与血清hsCRP水平无显著相关性(均P>0.05)。结论H.pylori根除治疗能有效改善慢性胃炎患者临床症状,提高H.pylori根除率,降低血清hsCRP水平,但会造成患者肠道菌群失调,且肠道菌群数量与血清hsCRP水平无显著相关性。     

根据“肠-肾轴”理论治疗慢性肾脏病的研究进展

有研究报道在慢性肾脏病的发生发展过程中可发现一系列肠道变化,并有学者用"肠-肾轴"理论阐述肾脏病中肠道的变化以及疾病过程中肾脏与肠道之间的联系,提示调节肠道菌群或可成为治疗慢性肾脏病的新方法。本文根据"肠-肾轴"理论,综述了在慢性肾脏病发展过程中肠道出现的变化,如肠内代谢物异常、肠道损伤以及肠道菌群失调等。以慢性肾脏病发生发展过程中肠道的异常变化为治疗切入点,总结了以大黄为主的中药在调节肠道功能、修复肠道屏障、纠正肠道代谢物异常等方面具有的显著疗效,为治疗慢性肾脏病及减少并发症等提供新的治疗思路和新方法。