EGF-PE4O重组毒素对喉鳞癌细胞株Hep-2的毒性作用

观察EGF－PE40重组毒素对喉鳞癌细胞的毒性作用,为寻找新型的治疗头颈鳞癌的生物制剂奠定基础。应用MTT比色法测定EGF－PE40重组毒素的生物学活性。并在光镜下观察Hep－2细胞形态变化。确定MTT比色法中Hep－2细胞浓度为2×104／well。选择10％SDS－0．01mol／LHCI作为MTT结晶的溶解液,当EGF－PE40重组毒素为0．53ng／ml时,50％的Hep－2细胞死亡,在一定范围内,随重组毒素增加,细胞损伤加重。     

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.     

膨体聚四氟乙烯填塞结合隆鼻手术治疗严重萎缩性鼻炎的临床观察#br#

目的　膨体聚四氟乙烯（expanded Polytetrafluoroethylene,e-PTFE）（简称膨体）填塞结合隆鼻手术综合治疗鼻中线低平的严重萎缩性鼻炎,提高疗效并改善患者生理及心理疾患。方法　收集联勤保障部队第九○八医院耳鼻咽喉头颈外科2010年1月至2021年1月期间确诊为萎缩性鼻炎患者50例,A组25例患者全部采用羟基磷灰石填塞法治疗,B组25例患者全部采用膨体填塞结合隆鼻手术综合治疗。采用鼻小柱切口,翻盖式手术切口暴露鼻中隔及鼻底部,在鼻腔内、下壁黏膜下填塞膨体及抬高鼻尖缩窄前鼻孔等综合治疗方法。结果　术后3个月、3~6个月除感染、外露手术失败者,A、B两组患者术后效果无统计学意义（P >0.05）,术后6~12个月后随诊B组满意率显著高于A组,鼻腔通气稳定,差异有统计学意义（P<0.05）。结论　膨体填塞结合隆鼻手术综合治疗鼻中线低平的严重萎缩性鼻炎,较唇龈切口黏骨膜下填入羟基磷灰石,长期效果稳定,患者满意度高,使用范围及前景更大,值得临床推广。     

儿童先天性腹内疝临床特点分析

目的 儿童先天性腹内疝(congenital internal hernias,CIH)是较为少见的疾病.本研究的目的是分析儿童先天性腹内疝的临床特点.方法 回顾性分析北京儿童医院2007年3月至2015年7月间收治的44例先天性腹内疝患儿的临床资料.结果 共有44例患儿被手术证实为先天性腹内疝.其中男24例,女孩20例,男女比例为1.2∶1.患儿的发病年龄为22 h至13岁,平均3.9岁.小于1岁患儿腹内疝共19例,占总例数的43.2％,其中新生儿病例9例占总例数的20.5％.根据手术所见将44例患儿分为3组:十二指肠旁疝(paraduodenal hernia,PH)组2例,肠系膜裂孔疝(transmesenteric hernia,TH)组34例,腹腔内先天性索带所致内疝(hernia due to congenital liga-ment,CLH)组8例.十二指肠旁疝患儿的发病年龄为11.9岁,显著大于肠系膜裂孔疝组3.35岁(P=0.005)和先天性索带致内疝组4.05岁(P=0.009).腹内疝的主要症状包括腹痛(n=31,70.4％)、呕吐(n=35,79.5％)、血便(n=3,6.8％)、腹泻(n=2,4.5％)等;每个临床症状各组间差异无统计学意义.术前有31例患儿接受腹部B型超声检查,其中21(67.7％)例患儿术前超声明确诊断内疝.手术中发现33(75.0％)例患儿有肠管坏死,TH组88.2％ (30/34)的患儿疝人肠管坏死,显著高于PH组(0/2,P=0.024)和CLH组(1/8,P＜0.001).结论 儿童先天性腹内疝是临床上一种少见的疾病.尽管术前很难明确诊断,但及时的手术治疗可取得很好的疗效.     

Mechanisms of the Bushen Huoxue formula in the treatment of osteoarthritis based on network pharmacology-molecular targets

Background:Osteoarthritis is a common degenerative disease with a high incidence, high disability rate, and poor prognosis. Clinical studies have shown that Bushen Huoxue formula can relieve joint swelling and pain and improve limb function and joint mobility, but there is a lack of high-quality scientific basis. Using network pharmacology and molecular docking technology to study the mechanism of Bushen Huoxue formula in the treatment of osteoarthritis.Methods:First, the active ingredients and corresponding target predictions of the formula were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the China National Knowledge Infrastructure. Meanwhile, the osteoarthritis disease targets were obtained through the genome annotation database platform (GeneCards) and the DrugBank database, and the target proteins obtained above were standardized using the Uniprot (https://www.uniprot.org) database standardization of names. Then, the Venn diagram was created by taking the intersection of the active ingredient and the target of the disease, and the “active ingredient-target” network was constructed and analyzed using Cytoscape 3.7.2 software. At the same time, the intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins database to build a protein-protein interaction network and to screen the core targets; the intersecting targets were visualized by using the Database for Annotation, Visualization and Integrated Discovery 6.8 database for gene ontology functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and construct the “active ingredient-target-pathway” network. Finally, the main active ingredients of the formula for tonifying the kidney and invigorating the blood were validated by molecular docking with the core targets.Results:A total of 194 active ingredients and 365 targets of the Bushen Huoxue formula were collected, 776 targets for osteoarthritis diseases and 96 targets for the intersection of active ingredients and diseases. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 104 relevant pathways, including tumor necrosis factor signaling pathways, cancer signaling pathways, nucleotide-binding oligomerization domain-like receptor signaling pathways, Toll-like receptors signaling pathways, and osteoclast differentiation, apoptosis, T-cell receptor signaling pathway, and other related pathways. The molecular docking results showed good binding of the main active ingredients to the core targets.Conclusion:This study shows that the treatment of osteoarthritis involves multicomponent, multitarget, and multipathway processes. The mechanism of anti-inflammatory, antioxidant, inhibition of cartilage matrix degradation, and reduction of subchondral bone destruction may be an important mechanism for the therapeutic effect.     

认知行为疗法对化疗癌症患儿治疗依从性及免疫功能的影响

目的：探讨认知行为疗法对化疗癌症患儿治疗依从性及免疫功能的影响,为癌症患儿的心理护理提供依据。方法：采用便利抽样方法选取符合标准的癌症患儿50例,并按照癌症类型、分期和年龄进行配对,根据其意愿分为治疗组和对照组各25例。对照组只采用常规心理护理,治疗组采用认知行为疗法,干预时间共5周。干预前后,采用Frankl依从量表（Frankl compliance scale,FCS）、Houpt行为量表（Houpt behavior scale,HBS）和外周血淋巴细胞含量（peripheral blood lymphocyte content,PBLC）评估其治疗依从性及免疫功能,并对结果进行比较分析。结果：干预后,治疗组的治疗依从性（3.20±0.40）、NK细胞含量（natural kill cell,NKC;20.36±10.76）明显高于对照组的治疗依从性（2.72±0.61）及NK细胞含量（16.68±8.44）,且差异具有统计学意义（t治疗依从性=3.256,P=0.002;t NK细胞含量=2.356,P=0.024）。T淋巴细胞含量较干预前明显增加（72.26±11.34 vs. 76.33±11.07;t=2.460,P=0.021）,但对照组干预前后在治疗依从性及淋巴细胞含量上并无明显差异（均P >0.05）。结论：认知行为疗法通过纠正患儿对患癌事件的歪曲认知,可以增强治疗依从性,对提高免疫调节能力及改善预后有一定的积极作用。     

新天然来源抗生素-抗霉素A_(18)的抗肿瘤活性及其产生菌I07A-01824的生物学特征

目的检测抗霉素A18的体外抗肿瘤活性并对其产生菌I07A-01824的形态及培养特征,生理生化特征等进行研究。方法用MTT法检测抗霉素A18的肿瘤细胞生长抑制作用,用流式细胞术测定其对细胞周期的影响;按分类学常规方法研究菌株I07A-01824的形态及部分生理生化特征。结果抗霉素A18能够抑制人肝癌细胞HepG2、人口腔上皮癌细胞KB的生长;这两个细胞株均被阻滞在细胞周期的S期。菌株I07A-01824的形态及培养特征与已知种——黄白链霉菌(Streptomyces albidoflavus)一致。结论红树林内生放线菌是新抗生素的重要来源。     

Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes

AIM: The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes. METHODS: The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3beta(GSK-3 beta), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3. RESULTS: Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt, as well as GSK-3beta. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action. CONCLUSION: The major function of resistin on liver is to induce insulin resistance. SOCS-3 induction may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes.     

L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition

Type 4 phosphodiesterases (PDE4) inhibitors are emerging therapeutics in the treatment of a number of chronic disorders including asthma, chronic obstructive pulmonary disease (COPD) and cognitive disorders. This study delineates the preclinical profile of L-454,560, which is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. In contrast to the exclusive binding of cilomilast and the preferential binding of roflumilast to the PDE4 holoenzyme state (Mg2+-bound form), L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM. L-454,560 was also found to be efficacious in two models of airway hyper-reactivity, the ovalbumin (OVA) sensitized and challenged guinea pig and the ascaris sensitized sheep model. Furthermore, L-454560 was also effective in improving performance in the delayed matching to position (DMTP) version of the Morris watermaze, at a dose removed from that associated with potential emesis. Therefore, L-454,560 is a novel PDE4 inhibitor with an overall in vivo efficacy profile at least comparable to roflumilast and clearly superior to cilomilast.     

不同部位创伤性皮瓣修复对指腹缺损患者痛觉和感觉情况的对比研究

目的 研究对比不同部位创伤性皮瓣修复对指腹缺损患者痛觉和感觉情况的影响.方法 我院从2012年7月至2013年7月收治的发生指腹缺损者共86例患者86指,随机分为观察组和对照组.对照组给予腹部皮瓣修复术,观察组实施邻指皮瓣修复术.对比两组患者断蒂时间及两点识别值,术后痛觉、感觉恢复情况及其对手术效果满意度情况.结果 观察组术后断蒂时间及两点识别值显著小于对照组,术后痛觉、感觉恢复情况显著优于对照组,患者对手术效果满意度显著高于对照组,差异均有统计学意义（均P＜ 0.05）.结论 应用临指皮瓣修复术治疗指腹缺损,手术效果更好,且患者伤指术后痛觉及感觉恢复更佳,值得临床推荐.