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.     

Dynamic Interactions of Post Cleaved NS2B Cofactor and NS3 Protease Identified by Integrative Structural Approaches

Diseases caused by flaviviruses such as dengue virus (DENV) and West Nile Virus (WNV), are a serious threat to public health. The flavivirus single-stranded RNA genome is translated into a polyprotein which is cleaved into three structural proteins and seven non-structural proteins by the viral and cellular proteases. Non-structural (NS) protein 3 is a multifunctional protein that has N-terminal protease and C-terminal helicase domains. The NS3 protease requires co-factor NS2B for enzymatic activity and folding. Due to its essential role in viral replication, NS2B-NS3 protease is an attractive target for antiviral drugs. Despite the availability of crystal structures, dynamic interactions of the N- and C-termini of NS2B co-factor have been elusive due to their flexible fold. In this study, we employ integrative structural approaches combined with biochemical assays to elucidate the dynamic interactions of the flexible DENV4 NS2B and NS3 N- and C-termini. We captured the crystal structure of self-cleaved DENV4 NS2B₄₇NS3 protease in post cleavage state. The intermediate conformation adopted in the reported structure can be targeted by allosteric inhibitors. Comparison of our new findings from DENV4 against previously studied ZIKV NS2B-NS3 proteins reveals differences in NS2B-NS3 function between the two viruses. No inhibition of protease activity was observed for unlinked DENV NS2B-NS3 in presence of the cleavage site while ZIKV NS2B-NS3 cleavage inhibits protease activity. Another difference is that binding of the NS2B C-terminus to DENV4 eNS2B₄₇NS3Pro active site is mediated via interactions with P4-P6 residues while for ZIKV, the binding of NS2B C-terminus to active site is mediated by P1-P3 residues. The mapping of NS2B N- and C-termini with NS3 indicates that these intermolecular interactions occur mainly on the beta-barrel 2 of the NS3 protease domain. Our integrative approach enables a comprehensive understanding of the folding and dynamic interactions of DENV NS3 protease and its cofactor NS2B.     

基质金属蛋白酶-1降解兔眼增殖性玻璃体视网膜病变增殖膜的实验研究

目的：评价基质金属蛋白酶-1（MMP-1）对增殖性玻璃体视网膜病变（PVR）增殖膜的降解作用。方法：健康成年有色家兔30只,用富含血小板血浆（PRP）诱导双眼PVR模型,各组玻璃体腔注入组织型纤溶酶原激活剂（t-PA）,15 min后注入MMP-1,行PVR分级评分,光镜观察视网膜结构。结果：注药后增殖膜发生较明显降解,各时间点PVR级别与对照组相比,差异有统计学意义（P〈0.01）。结论：一定剂量的MMP-1玻璃体腔注射能对实验性PVR的增殖膜产生降解作用。     

环孢素A对大鼠骨折愈合的影响

目的探讨环孢素A(CsA)对大鼠骨折愈合的影响。方法 25只右侧股骨干横行骨折大鼠随机分成2组,实验组15只,对照组10只。实验组骨折当天皮下注射CsA 1.5mg/kg,对照组皮下注射生理盐水1ml,共注射8周,检测股骨干骨密度和生物力学性能检测。结果实验组和对照组右侧股骨干的骨折愈合后,其力学性能参数最大扭力、最大转角和能量吸收仍显著小于各自左侧正常股骨干。实验组右侧股骨干骨折愈合后的最大扭力、最大转角、抗扭刚度和能量吸收与对照组比较均无显著差异,骨折端骨密度也无显著差异。结论 1.5mg/kg剂量的CsA对股骨干骨折愈合无显著影响。     

全麻快诱导期非加压通气的可行性

目的观察丙泊酚-爱可松-瑞芬太尼快诱导期非正压通气的可行性及对急性胃扩张的预防效果。方法20例择期全麻病人入手术室即作动脉血气分析,高流量(8~10L/m in)吸氧5m in后静注丙泊酚(2mg/kg)-爱可松(0.8mg/kg)-瑞芬太尼(1μg/kg)序贯快诱导(60 s内注射完毕),60 s后气管插管。插管成功即刻再进行动脉血气分析。诱导插管期间任由患者进入无呼吸状态而不给予正压辅助通气。结果各病人诱导后插管条件满意,平均插管耗时27.45 s。诱导插管后患者的PaO2、PaCO2均上升,与基础值相比分别为(242±111)Vs(93±10)mm Hg(P<0.01)和(45±8)Vs(39±4)mm Hg(P<0.01),无急性胃扩张发生。结论经5m in的高流量纯氧预吸后,丙泊酚-爱可松-瑞芬太尼快诱导插管期无通气并无低氧、高碳酸血症的发生,且可有效防止诱导期急性胃扩张发生。     

肾缺血再灌注后脑脊液中自由基的变化

目的探讨脑脊液中自由基在肾缺血再灌注(I/R)损伤后的变化规律。方法20只健康新西兰兔随机分为对照组和肾I/R组,检测和比较I/R后24h脑脊液中尿素氮(BUN)、肌酐(Cr)、超氧化物歧化酶(SOD)和丙二醛(MDA)的含量。结果与对照组相比,在肾I/R后24hIR组脑脊液中的BUN、Cr和MDA均升高(P<0.05),I/R组脑脊液SOD活性降低(P<0.05)。结论肾I/R损伤后,脑脊液和脑组织中代谢废物积聚同时自由基生成增多,提示肾I/R损伤后神经系统功能的改变可能与其相关。     

艾滋病相关淋巴结病理改变及其与淋巴结中CD4+CD25+调节性T细胞的相关性

目的探讨艾滋病患者淋巴结组织中CD4 CD25 调节性T细胞的表达、分布及其与病理改变的相关性。方法对22例活检及13例尸体解剖的HIV/AIDS患者的淋巴结进行组织学观察和病理分期,采用免疫组织化学法对淋巴结组织中的CD4 CD25 调节性T细胞特异性标记物FoxP3进行检测。结果35例艾滋病患者的淋巴结中,1～4期分别有5、4、14和12例。所有淋巴结组织中均检测出FoxP3的阳性表达;在1、2期病变淋巴结内,FoxP3阳性细胞数量较多,分布于滤泡间区和副皮质区;3、4期随着淋巴细胞的数量衰竭,阳性细胞数量的减少更加明显。结论艾滋病患者淋巴结中存在有CD4 CD25 调节性T细胞,随着淋巴结病变的进展其数量减少或耗竭。     

一起致病性大肠埃希氏菌引致食源性疾病爆发的调查

目的:了解一起食源性疾病暴发的原因.方法:采用流行病学调查及实验室分离培养确认致病原.结果:在3份病人肛试子和3份末梢水中检出有致病性大肠埃希氏菌,未检出其它致病菌.一日三餐均饮用该水的教师和家属发病率为66.67%,而在校一日只进一餐的学生发病率为26.23%,前者显著高于后者(χ2=52.63,P<0.01).当地场镇居民只用不饮此水未见发病.结论:通过流行病学调查和实验室病原学检查,证实本起疫情系一起致病性大肠埃希氏菌引起的食源性疾病暴发疫情.     

Detection of immunoglobulin gene rearrangement in leukemia by seminested PCR amplification and Southern blot hybridization

ＤｅｔｅｃｔｉｏｎｏｆｉｍｍｕｎｏｇｌｏｂｕｌｉｎｇｅｎｅｒｅａｒｒａｎｇｅｍｅｎｔｉｎｌｅｕｋｅｍｉａｂｙｓｅｍｉｎｅｓｔｅｄＰＣＲａｍｐｌｉｆｉｃａｔｉｏｎａｎｄＳｏｕｔｈｅｒｎｂｌｏｔｈｙｂｒｉｄｉｚａｔｉｏｎＸｕＢｉｎｇ（徐兵）；ＺｈｏｕＳｈ...     

下腔静脉滤器植入术在防治肺动脉栓塞中的应用

目的 探讨下腔静脉滤器植入术在防治肺动脉栓塞中的价值。方法 回顾性分析1998年8月—2003年6月间实施的61例下腔静脉滤器植入术防治肺动脉栓塞的临床资料。结果 临时性下腔静脉滤器植入11例，永久性下腔静脉滤器50例。随访3～66个月，平均38个月。61只下腔静脉滤器均展开良好，有1例临时滤器移位至下腔静脉近心端，其他无移位。临时滤器体内置放时间2～4周取出。1例永久性滤器植入14个月后滤器中血栓形成。均未再发生肺动脉栓塞。结论 下腔静脉滤器植入术确能有效预防肺动脉栓塞，但应严格掌握适应症。