Paired immunoglobulin-like receptor B (PirB) has been identified as a new receptor for myelin-associated inhibitory (MAI) proteins, which may play important role in axonal regeneration and corticospinal tract (CST) projection associated with neurobehavioral function recovery after stroke. Here, we found that the expression of PirB was increased in the cortical penumbra from 1 to 28 days after transient focal cerebral ischemic reperfusion of rats. Then, transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated that might block the interactions between MAIs and PirB. The results showed that TAT-PEP displayed high affinity for MAIs and ameliorated their inhibitory effect on neurite growth. Furthermore, TAT-PEP can widely distribute in the penumbra after intraperitoneal injection. Then, we found that TAT-PEP enhanced neurite growth and alleviated growth cone collapse after oxygen glucose deprivation (OGD) injury. In addition, TAT-PEP promoted long-term neurobehavioral functional recovery through enhancing axonal regeneration and CST projection. Finally, the observations demonstrated that POSH/RhoA/growth-associated protein 43 (GAP43) as PirB-associated downstream signaling molecules played important role in neurobehavioral functional recovery after stroke. Moreover, the underlying mechanism associated with TAT-PEP-mediated promoting axonal regeneration and CST projection was by intervening in the expression of POSH, RhoA, and GAP43. These studies suggest that TAT-PEP may represent an attractive therapeutic strategy against stroke.

BACKGROUND:Given the potential role of brown adipose tissue (BAT) in stimulating energy expenditure, activating BAT can be an effective anti-obesity treatment. Here, we aimed to use adenoviruses to establish the effect of the inducible degrader of the low density lipoprotein receptor (IDOL) in the formation of BAT. METHODS:IDOL or green fluorescent protein was overexpressed by adenovirus and injected into the scapula of C57BL/6J mice and fed with high-fat diet for 12 weeks. We measured the body weight, morphology of lipid droplets, lipid profiles and adipogenesis protein expression levels. BAT was isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, we conducted western blot to verify the authenticity and reliability of the RNA sequencing results. RESULTS:Compared with the control group, IDOL overexpression led to a significant reduction in body weight, consistent with the weight of adipose tissues and organs. Further studies show IDOL promotion increased ATGL, perilipin 1 and UCP-1 expression in BAT. However, perilipin 1 protein expression was significantly reduced in the Ad-IDOL group in epididymal white adipose tissue, while there was no significant difference in adiponectin, ATGL and perilipin 1 protein expression in inguinal white adipose tissue. Notably, serum FGF21 and leptin protein expression were negatively related to the adipose tissue decrease after Ad-IDOL administration. RNA sequencing analysis identified 1256 differentially expressed genes that were prominently enriched across nine signalling pathways. Additionally, the protein expression of PGAM2, G6PC1 and phosphorylation-AMPK was significantly increased after overexpression IDOL in BAT, which was consistent with the results of the RNA sequencing analysis. CONCLUSIONS:Our research demonstrated that IDOL overexpression alleviates the body weight by promoting the phosphorylation of AMPK to upregulate the UCP-1 and ATGL exacerbating lipolysis in BAT.

Background: C1q/tumor necrosis factor-related protein-9 (CTRP9) is critically involved in the pathophysiology of metabolic and cardiovascular disorders. This investigation aimed to clarify the mechanism underlying the role of CTRP9 in atherosclerosis in apolipoprotein E (ApoE) knockout (KO) mice. Methods: ApoE KO mice were fed a Western diet and injected with a virus which resulted in CTRP9 overexpression or knockdown for 12 weeks. The plasma lipid levels and atherosclerotic plaque areas were measured after the mice were euthanized. Aortas were isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, plasma oxidative stress factors were measured to demonstrate the reliability of the RNA sequencing results. Results: The plasma lipid levels in the CTRP9 overexpression group did not significantly differ from those in the green fluorescence protein (GFP) group. Markablely, CTRP9 overexpression inhibited atherosclerotic plaque formation in ApoE KO mice, whereas CTRP9 knockdown promoted plaque formation. RNA sequencing analysis identified 3485 differentially expressed genes that were prominently enriched across 55 signaling pathways. Additionally, plasma oxidative stress factors were significantly reduced after CTRP9 overexpression, whereas these factors were increased after CTRP9 knockdown, which was consistent with the results of the RNA sequencing analysis. Conclusions: These findings demonstrated that CTRP9 alleviated inflammation and cholesterol metabolism, which reduced oxidative stress in an atherosclerotic animal model. These beneficial effects may mediate the suppression of lesion development in the aorta.

The APPswe/PS1ΔE9 mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly APPswe/PS1ΔE9 mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer.

Abstract Background Hydrogen has been proven to play a protective role in vivo by its biological effects such as anti-oxidant, anti-inflammatory. Allergic contact dermatitis (ACD) is a common inflammatory skin disease characterized by itching, skin inflammation, and allergic responses. ACD is caused by T cell-mediated delayed type hypersensitivity. Results The aim of this study is to investigate the ameliorative effect of Coral calcium hydrogenated (CCH) which releases hydrogen slowly in the body and has more advantages than the direct use of hydrogen. 2,4-Dinitrochlorobenzene (DNCB) was applied for ACD induction. CCH was applied by intragastric administration. Dermatitis score and number of scratches were significantly diminished in CCH-treated groups. Especially, CCH showed inhibitory effects on skin lesion and hyperplasia. Additionally, splenic coefficient and plasma IgE were significantly inhibited by CCH. Conclusions Those findings suggested CCH has a remarkable effect on DNCB-induced ACD in mice.

麻醉学是伴随着舒适化医疗的需求而诞生的,实现医疗的舒适化始终是麻醉学最根本的历史使命.近年来,麻醉学科迅速发展,在不断拓展舒适化医疗服务领域的同时,也积极助力健康中国发展战略.然而,目前麻醉学科发展水平与舒适化医疗需求之间的矛盾仍然存在,大众对舒适化医疗的需求和对麻醉学的理解认识之间仍存在严重偏差,舒适化医疗的运行模式和配套机制尚需进一步优化.相信通过各界的共同努力,麻醉学服务领域将不断延伸,内涵将不断提升,从而为广大人民群众提供更高效、优质的舒适化医疗保健.

原发性三叉神经痛(P TN)是一种在头面部、口腔内三叉神经分布区域内的阵发性剧烈疼痛.中医属于"面痛"范畴,多与外感邪气、情志不调等因素有关.西医认为本病与感觉性癫痫样发作、微血管压迫神经、解剖结构异常等有关.该病发病率不高,诊断并不困难,但治疗较为棘手,疗效不够理想.为明确P TN的诊治理论知识,推广临床非手术治疗经验,提高P TN的诊疗效果,预防减少P TN的反复发作,本文参考国内外文献,结合专家经验,对P TN的病因、临床表现、辨证分型、治疗方案、疗效评价以及预防保健方面分别从西医和中医角度进行阐述并制定原发性三叉神经痛中西医非手术诊疗方法的专家共识.

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets.

分泌卷曲相关蛋白4(SFRP4)是Wnt信号通路的抑制因子,在人类个体发育过程中发挥重要作用.同时,SFRP4基因表达和蛋白分泌异常导致机体发生病理变化.本文介绍了SFRP4基因和蛋白的结构特征、组织分布以及胚胎发育过程中的表达变化.临床研究发现,糖尿病患者血清中SFRP4蛋白水平显著升高,其与胰岛素分泌呈负相关.作为Wnt信号通路的抑制因子,SFRP4在调控脂肪形成、糖代谢以及胰岛素抵抗等生理和病理生理过程中扮演着重要角色.近年来,SFRP4在肥胖、脂质代谢紊乱以及糖尿病发生中的病理作用引起了广泛关注,并取得了重要进展.对其进一步系统深入的研究,不仅可以揭示肥胖、脂质代谢紊乱和糖尿病发生的新机制,也有望发现临床药物治疗新靶点.

The aging of the immune system is not only an inevitable result but also an important cause of physical aging. The aging of the immune system is rooted in the aging of hematopoietic cells (HSCs), which manifests as decreasing functionality of the adaptive immune system and the innate immune system. C57BL/6 mice of different ages were collected in this study to better understand the changes in the structures of the innate and adaptive immune systems in individuals of different ages and the distribution and changes in immune cells with stem cell properties. The immune cells of the innate and adaptive immune systems, including DCs, monocytes, macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes, were assessed, and the proportions of cells with stem cell properties among these immune cell populations were also tested. Overall, immune cells in the peripheral blood, spleen, and bone marrow of mice exhibit certain regular properties with increasing age. The trend of changes in immune cells in different immune organs differs with age. The changes in lymphocytes in the peripheral blood are more sensitive. Their proportions increase slowly with age and then decrease rapidly to a very low level (less than 5%) after a certain point (9 or 13 months old). Nine to 13 months of age is the most critical time point for assessing changes in the immune system of mice and the most critical time point for detecting changes in the proportion of stem cells. After 13 months of age, the balance and stability of stem cells in mice are disrupted, and animals begin to age rapidly. The ratio of Ly6A to E+CD117+ cells in the peripheral blood, particularly lymphocytes involved in adaptive immunity, represents a specific marker for predicting immune senescence and body senescence.

目的 制作肝脏特异性高表达分泌卷曲相关蛋白4(SFRP4)的转基因小鼠,并对其生物学特性进行分析.方法 利用显微注射方法制作SFRP4转基因小鼠,采用Western blotting和qRT-PCR技术鉴定模型小鼠中SFRP4转基因的表达水平.结果 PCR结果 显示,成功获得SFRP4转基因小鼠,SFRP4转入基因主要在肝脏中表达,肝脏组织中SFRP4基因和蛋白表达水平与野生型同窝对照组相比明显升高.结论 成功建立了高表达SFRP4的转基因小鼠,为研究SFRP4基因功能和参与代谢性疾病的机制提供了良好的动物模型.

Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of frizzled proteins. In the present report, the effects of SFRP4 on murine brown adipocyte differentiation were evaluated, which exhibited an intrinsic capacity to differentiate with high efficiency. Brown preadipocytes were isolated from the scapular region of brown adipose tissue, which showed that the overexpression of recombinant active SFRP4 protein at three concentrations (1, 10 and 100 ng/ml) significantly increased the expression of adipocyte differentiation-associated genes (C/EBPα, C/EBPβ, UCP-1, PRDM16, PGC1α and GLUT4) in a dose-dependent manner compared with the control group. Secondly, adiponectin protein expression was significantly inhibited in a dose-independent manner, while leptin was increased in brown adipocytes by incubation with the high concentration (100 ng/ml) of SFRP4. Thirdly, the role of interleukin-1β (IL-1β) was investigated in brown adipocytes and discovered that IL-1β cannot induce SFRP4 mRNA expression in brown adipocytes, similar to human islet cells. These data suggested that SFRP4-treated brown adipocytes represent a valuable in vitro model for the study of adipogenesis and indicated that SFRP4 served various functions during brown adipocyte differentiation.

Cancer is a key cause of death worldwide. Despite the development of radiotherapy, chemotherapy and even immunotherapy, surgery remains the standard treatment for cancer patients. Recently, many studies have shown that propofol, a commonly used anesthetic drug, can affect the prognosis of cancer. In this review, we provide an overview of the molecular mechanisms of propofol in the development of cancer. Propofol not only affects epigenetic pathways, such as those involving miRNA, lncRNA and histone acetylation, but also modulates genetic signaling pathways, including the hypoxia, NF-κB, MAPK, SLUG and Nrf2 pathways. In addition, propofol influences the immune function of patients and impacts the degree of immunosuppression. Furthermore, we briefly summarize the clinical trials on the effect of propofol in cancer development. Ultimately, further studies distinguishing the types of tumors in clinical trials are needed to clarify the correlation between propofol and cancer.

目的 研究可可粉对雌性ApoE-/-小鼠主动脉动脉粥样硬化斑块形成的影响.方法 以雌性ApoE-/-小鼠为研究对象,按照随机对照表将小鼠(45只)随机分为3组:对照组(高脂高胆固醇饮食)、低剂量组(高脂高胆固醇+0.2％可可粉饲喂)、高剂量组(高脂高胆固醇+2％可可粉饲喂),每组各15只.相应饮食饲喂小鼠12周,观察各组小鼠体重、肝脏重量、肝脏重量/体重;检测小鼠血浆血脂指标(TG、TC、LDL-C和HDL-C)的水平;HE和油红O染色分析小鼠主动脉的病理变化及斑块面积.结果 3组小鼠的体重、肝脏重量、肝脏重量/体重、TG、TC和主动脉根部斑块面积差异均无统计学意义(P>0.05);与对照组比较,低、高剂量组的HDL-C水平显著升高,LDL-C水平显著降低,主动脉斑块面积显著减少.结论 可可粉能够有效抑制雌性ApoE-/-小鼠主动脉动脉硬化斑块形成,这可能与其改善机体血脂水平有关.

The stress response can be triggered during the perioperative period by tension, fear, anesthesia, surgical trauma, and various postoperative adverse stimuli, leading to significant changes in the endocrine, metabolic, and immune systems of patients. In particular, immunosuppression induced by the stress response has adverse effects on the postoperative recovery of patients. As acupuncture stimulation-related technologies have been rapidly developed and applied in recent years, a number of basic and clinical studies have confirmed that acupoint stimulation can regulate the immune system via local, neurological, and endocrine pathways. Moreover, acupoint stimulation treatment has also been shown to reduce the adverse effects of immunosuppression by affecting the release of various cytokines, such as interleukin (IL) 1, IL-2, IL-4, IL-6, IL-10, IFN-γ, and tumor necrosis factor (TNF) β, immunoglobulins, complement proteins, and T cell markers such as CD3, CD4, and CD4/CD8 via the regulation of macrophages, neutrophils, NK cells, and endogenous opioids. In addition, acupuncture stimulation treatment during the perioperative period can also significantly decrease the amount of anesthetic required for anesthesia, effectively reduce nausea and vomiting, relieve post-operative pain, and accelerate the recovery of physiological functions. Therefore, acupuncture stimulation treatment has shown important potential for clinical applications.

目的:研究复方甘菊利多卡因(Compound Chamomile and Lidocaine,CCL)对口腔溃疡的促愈合作用及发挥临床治疗作用的可能药理机制.方法:化学灼烧法建立新西兰兔口腔溃疡动物模型,每日各组分别涂抹CCL、成纤维生长因子(basic fibroblast growth factor,bFGF)3次,记录口腔溃疡面积;3、5、7d取溃疡组织固定,HE染色进行组织病理学观察;免疫组化检测各组IL-8、TNF-α和SOD的表达差异.抑菌环实验评价CCL对金黄色葡萄球菌、大肠埃希菌的抑菌能力.结果:CCL对兔口腔溃疡的促愈合作用不明显,7 d CCL组溃疡区虽可见增生的移行上皮层,结缔组织内仍见大量炎症细胞;但免疫组化显示,CCL组中IL-8,SOD表达水平接近bFGF组,均显著低于空白对照组(P<0.05);抑菌环实验显示,CCL对金黄色葡萄球菌和大肠埃希菌的抑菌作用与金霉素相当,与bFGF凝胶相比具有绝对的抑菌优势(P<0.001).结论:除了具有明确的止痛作用外,降低某些炎症因子的表达及加强局部的抗感染能力可能是CCL发挥临床治疗作用的主要机制.

This study was designed to investigate the neuroprotective effect of hyperoxygenate hydrogen-rich saline (HOHS) against brain injury induced by carbon monoxide (CO) poisoning in rats. A rat model of CO poisoning was established by administering CO via intraperitoneal injection to male Sprague-Dawley rats. Forty-eight adult male rats were randomly divided into the following groups: normal control group (NG), CO poisoning group (CO), HOS treatment group (hyperoxygenated solution, HOS) and HOHS treatment group (HOHS). After CO poisoning, the carboxyhemoglobin (COHb) contents in the blood of rats in all the CO poisoning groups were increased significantly. However, HOS and HOHS significantly decreased COHb contents, furthermore, the HOHS group had lower COHb contents than the HOS group. Arterial oxygen partial pressure (PaO2) and arterial oxygen saturation (SaO2) results showed that HOS and HOHS could improve the oxygenation of the rats with CO poisoning. Compared with the CO group, the HOS group and the HOHS group had persistently neuroprotective effect on CO-induced brain injury, as assessed by modified neurological severity score (mNSS), furthermore, the HOHS group had better neurological functional recovery than the HOS group. The neuronal apoptosis induced by CO was also evaluated. Except the NG group, all the CO-poisoning groups had varying degrees of neuronal apoptosis. There was lesser degree of neuronal apoptosis in both the HOS group and the HOHS group than that in the CO group. Moreover, the HOHS group had more minor degree of neuronal apoptosis than the HOS group. Compared with the CO group, the free radicals production in the HOS group and the HOHS group were significantly inhibited. In addition, there were significantly difference in the free radicals production between the HOS group and the HOHS group. We could conclude that HOHS exerted a stronger neuroprotective effect against CO-induced brain injury than HOS, and the neuroprotective mechanism of HOHS may be related with inhibition of both neuronal apoptosis and free radicals.

Background: Hemorrhagic shock could induce acute lung injury (ALI), which is associated with cell hypoxia, lung tissue inflammation, free radical damage, and excessive cell apoptosis. Our previous studies demonstrated that hyperoxygenated solution could alleviate cell hypoxia. Furthermore, hydrogen-rich solution (HS) could relieve lung tissue inflammation, free radical damage and excessive cell apoptosis. Therefore we hypothesize that Hyperoxygenated Hydrogen-rich solution (HOHS) can protect the lung against ALI. Materials and methods: SD rats were randomly divided into five groups (n = 6 at each time point in each group) and were exposed to Hemorrhagic shock induced ALI, and then treated with lactated Ringer's solution (LRS), hyperoxygenated solution, HS, and HOHS, respectively. The protective effects of these solutions were assessed using methods as follows: arterial blood samples were collected for blood gas analysis; Bronchoalveolar lavage fluid was collected for cell count and protein quantification; lung tissue samples were collected to measure wet/dry ratio, as well as levels of T-SOD, MDA, TNF-alpha, and IL-6; Caspase-3 and TUNEL-positive cells, and pathological changes were observed under light microscope; ALI was scored using the Smith scoring method; ultrastructural changes of lung tissues were further observed with transmission electron microscopy. Results: The results indicated that PaO2, PaCO2, and T-SOD increased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group; and conversely that the levels of lactate, MDA, TNF-alpha and IL-6, cell count, protein content, caspase-3 and TUNEL-positive cells as well as ALI score decreased in the three treatment groups (P < 0.05), most significantly in the HOHS group (P < 0.01) compared with the LRS group. Morphological observation with optical microscope and electron microscopy showed that compared with the LRS group, cell damage in the three treatment groups improved to a varying extent, especially evident in the HOHS group. Conclusions: These findings demonstrate that HOHS can protect the lung against ALI induced by hemorrhagic shock. (C) 2019 Elsevier Inc. All rights reserved.