The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

Temporal Dynamics of the Intestinal Microbiome Following Short-Term Dietary Restriction

Short-term dietary restriction has been proposed as an intriguing pre-operative conditioning strategy designed to attenuate the surgical stress response and improve outcomes. However, it is unclear how this nutritional intervention influences the microbiome, which is known to modulate the systemic condition. Healthy individuals were recruited to participate in a four-day, 70% protein-restricted, 30% calorie-restricted diet, and stool samples were collected at baseline, after the restricted diet, and after resuming normal food intake. Taxonomy and functional pathway analysis was performed via shotgun metagenomic sequencing, prevalence filtering, and differential abundance analysis. High prevalence species were altered by the dietary intervention but quickly returned to baseline after restarting a regular diet. Composition and functional changes after the restricted diet included the decreased relative abundance of commensal bacteria and a catabolic phenotype. Notable species changes included Faecalibacterium prausnitzii and Roseburia intestinalis, which are major butyrate producers within the colon and are characteristically decreased in many disease states. The macronutrient components of the diet might have influenced these changes. We conclude that short-term dietary restriction modulates the ecology of the gut microbiome, with this modulation being characterized by a relative dysbiosis.     

Effects of Lactobacillus casei on Iron Metabolism and Intestinal Microflora in Rats Exposed to Alcohol and Iron

Background:Higher alcohol consumption was reported in those who consumed more red meat. Both excessive alcohol and iron intake can cause damage to the liver. The purpose of this study is to investigate the effect of Lactobacillus casei strain Shirota (L. casei) on iron metabolism and intestinal microflora in rats after alcohol and iron co-exposure.Methods:Sixty male rats were randomly divided into 3 groups for 12 weeks: the control group: treated with normal saline by gavage and normal diet; the model group: treated with alcohol (8-12 mL/kg/day) by gavage and iron (1500 mg/kg) in diet; the model group supplemented with L. casei (8 × 10⁸ CFU/kg/day) as the L. casei group.Results:Compared with the control group, the levels of serum ferritin, hepcidin, the protein expressions of ferroportin 1 and divalent metal transporter 1 in the model group were significantly increased, while it was significantly decreased after L. casei supplement (P < .05). Compared with the control group, the amount of Lactobacillus of the model group was significantly decreased, while the amount of Bacteroides and Escherichia coli was significantly increased (P < .05). After the supplementation of L. casei, the amount of Lactobacillus increased significantly, while the amount of Bacteroides and E. coli decreased significantly (P < .05).Conclusion:L. casei could effectively improve iron metabolism and intestinal flora disorder induced by excessive alcohol and iron. The effective treatment of iron metabolism may be related to the changes of intestinal flora.     

复发性卵巢上皮癌再次肿瘤细胞减灭术的临床意义及影响预后的因素

目的探讨再次肿瘤细胞减灭术（secondarycytoreductivesurgery,SCS）在复发性卵巢上皮癌（简称卵巢癌）治疗中的作用及影响预后的因素。方法回顾性分析复发性卵巢癌107例,按其治疗方式分为3组：手术组（化疗＋SCS）41例,单纯化疗组47例,未治疗组19例。比较其中位生存期,分析影响预后的因素。结果手术组、单纯化疗组的中位生存时间分别为29、23个月,两组间差别有统计学意义（P〈0．05）,未治疗组中位生存时间为7个月,与其他两组相比有统计学差异（P〈0．05）。在手术组中,SCS后肉眼完全切除与未完全切除的中位生存时间相比差异具有统计学意义（P〈0．05）。多变量分析中,无疾病间期（disease—freeintervals,DFI）〉12个月、单个复发灶、最大复发灶直径≤5cm,再次手术残余灶肉眼完全切除的患者中位生存期明显延长。结论满意的SCS和二线化疗均可改善患者预后;实施SCS应遵循个体化原则,筛选适当的患者,以更好地提高患者生存质量。     

Reciprocal Interaction Between Intestinal Microbiota and Mucosal Lymphocyte in Cynomolgus Monkeys After Alemtuzumab Treatment

It has been known that the gut microbiota plays a central role in shaping normal mucosal immunity, however, little information is available whether the variability of mucosal lymphocytes impacts the commensal flora. Here, we applied a cynomolgus monkey model to characterize the structure and composition of the gut microbiota in response to lymphocyte depletion and to determine their potential association. Molecular profiling of 16S rDNA showed that the intestinal microbiota composition was perturbed after the depletion of mucosal lymphocytes and were recovered following the repopulation. Some specific bacteria from the orders Lactobacillales, Enterobacteriales and Clostridiales, and the genus Prevotella and Faecalibacterium, were primarily responsible for the variations of the gut microbiota after lymphocyte depletion. Interestingly, the species richness of the ileal mucosal microbiota was associated the proportions of TCRαβ⁺ or TCRγδ⁺ T cells (p < 0.01). We demonstrate for the first time the feature of intestinal microbiota composition after lymphocyte depletion and provide novel evidence that the perturbation of gut microbiota is associated with lymphocyte depletion. It may contribute to understand the relationship between gut commensal microbiota and mucosal immune system. Study results provide insight into biological activity of alemtuzumab in intestinal barrier in organ transplantation.     

机械性肠梗阻多层螺旋CT诊断及其临床意义

目的探讨多层螺旋CT（MSCT）对机械性肠梗阻的诊断价值及其临床意义。方法回顾分析2008年6月～2011年2月我院经手术及病理检查证实为机械性肠梗阻58例患者的MSCT扫描结果。结果MSCT初诊与手术病理或全愈随访复查相符54例,敏感性94．3％,特异性91．3％,准确率93．1％。引起梗阻的主要病因有肠粘连、肠肿瘤、肠扭转、肠套叠、结石及粪石等。不同原因引起机械性肠梗阻的MSCT影像表现各具特征。结论MSCT对机械性肠梗阻诊断及鉴别诊断具有重要的临床意义。     

上皮间质转化与肝癌微环境变化的关系

通过对上皮间质转化理论基础的回顾,探讨上皮间质转化、间质上皮转化与肝脏纤维化及肝癌干细胞转化的关系,从而寻找肝癌干细胞的相关基因、抗体标记物及关键通路,这不仅有利于肝细胞癌分期的诊断,提示预后,更为寻找医治肝癌的方法提供更多的研究方向。     

灯盏花素大鼠在体肠吸收动力学研究

目的 研究灯盏花素在大鼠肠道的吸收动力学。方法 进行大鼠在体肠循环灌流肠吸收实验，HPLC法测定灯盏花乙素，研究灯盏花素在小肠和结肠的吸收情况，并分别考察不同质量浓度和不同pH对小肠吸收的影响。结果胆管结扎与胆管不结扎的实验组之间，吸收速率常数（ka）和吸收百分率均有显著性差异，在小肠和结肠的ka分别为（0．1071±0．013O）和（0．0707±0．0089）h^-1；灯盏花素在不同质量浓度下，未发现饱和现象，其ka几乎保持不变，在pH6．0～7．4，灯盏花素的吸收不受pH的影响。结论 灯盏花素在小肠的吸收多于在结肠的吸收，其吸收机制为被动扩散，吸收过程为一级动力学过程，提示灯盏花素可以被制成口服缓释剂型。