简介:摘要目的探讨肾小球补体C1q及C3c沉积与糖尿病肾病进展的相关性。方法纳入2011年1月至2019年7月在南京医科大学第一附属医院确诊的2型糖尿病肾病患者112例,其中男性83例(74.1%),年龄(51.22±11.12)岁,随访时间19.0(8.5,31.3)个月。根据肾小球C1q和C3c是否沉积分为四组:C1q无沉积C3c无沉积组(n=38)、C1q无沉积C3c沉积组(n=24)、C1q沉积C3c无沉积组(n=14)和C1q沉积C3c沉积组(n=36),检测24 h尿蛋白等临床指标并收集病理资料。采用Cox回归及Kaplan-Meier生存曲线评估肾C1q和C3c沉积对肾脏预后的影响。结果四组间24 h尿蛋白差异有统计学意义[分别为1.84(0.92,3.89),4.19(2.09,6.50)3.30(1.84,6.70),3.64(2.49,7.22)g/24 h,P<0.01],C1q沉积C3c沉积组24 h尿蛋白定量显著高于C1q无沉积C3c无沉积组(P<0.01)。Kaplan-Meier生存曲线结果提示,四组累积生存率差异有统计学意义(Log-rank χ²=8.785,P<0.05),C1q沉积C3c无沉积组累计生存率最低,预后最差。调整后的多因素Cox分析显示,肾小球C1q和C3c共沉积[风险比(HR)2.260,95%可信区间1.329~3.845,P<0.01]、肾小球C1q+C3c+IgM均沉积(HR=4.142,95%可信区间 1.071~16.021,P<0.05)是肾脏预后的独立危险因素。结论肾小球C1q及C3c沉积与糖尿病肾病患者蛋白尿、较差的肾功能和预后不良相关,且肾小球C1q和C3c共沉积是糖尿病肾病进展的独立危险因素。
简介:摘要Müller细胞是视网膜主要的神经胶质细胞,对于维持视网膜稳态有重要作用。视网膜损伤后,斑马鱼Müller细胞可以通过重编程进入细胞周期增生并分化为神经元,促进视网膜完成再生修复。高等动物Müller细胞的这一能力几乎消失,导致视网膜损伤后神经元无法再生,最终造成视功能减退,甚至丢失。研究发现,虽然视网膜损伤后Müller细胞重编程过程在高等动物中不能自发激活,但可以通过诱导增强其重编程能力并实现其向神经元的转分化。这种神经元再生潜能使Müller细胞在高等动物视网膜修复再生中极有应用前景。本文围绕Müller细胞转分化为神经元的最新研究进展,从Müller细胞起源及生理病理状态、重编程机制、哺乳动物Müller细胞向神经元转分化的诱导方式、限制Müller细胞转分化为神经元的因素4个方面展开,并对Müller细胞重编程参与视网膜再生的优势与前景以及目前存在的问题进行总结。
简介:AbstractBackground:Aberrant activation of the complement system plays an important role in the pathogenesis and development of immunoglobulin A nephropathy (IgAN). The relationship between serum complement and the clinical-histopathological features and outcomes of IgAN is controversial. This retrospective study aimed to examine the relationship between the complement 3/4 (C3/C4) ratio and the clinicopathologic changes and prognosis of patients with IgAN.Methods:A total of 397 patients with primary IgAN from January 2007 to December 2012 at the Chinese People’s Liberation Army General Hospital were included in this study. The correlation test and Chi-square test or one-way analysis of variance test were performed to evaluate the relationship between the C3/C4 ratio and other clinical-pathological factors. Propensity score matching and a multivariate Cox regression model were used to calculate the risk factors of renal outcome.Results:The median follow-up period was 75 months. During the follow-up period, 62 patients (15.6%) developed into the end-stage renal disease (ESRD). The C3/C4 ratio at baseline was associated with the level of serum creatinine (SCr), 24 h urinary protein excretion (24 h Upre), global glomerular sclerosis, and tubulointerstitial lesion. The level of SCr and 24 h Upre and the degree of chronic kidney injury were statistically different among groups defined by different C3/C4 ratio levels. The survival rates of patients among groups with different C3/C4 ratio levels were different. After propensity score matching, eighty-eight pairs of patients were successfully matched, and the C3/C4 ratio was an influencing factor for the patients’ outcome (hazard ratio 0.587, 95% confidence interval 0.329-0.880). Patients with a C3/C4 ratio <3.6 had a poorer outcome compared with the others (P = 0.002).Conclusions:IgAN patients with decreased C3/C4 ratio displayed significantly more severe clinical symptoms and chronic renal injury than patients with higher ratios. A low C3/C4 ratio could be a risk factor for patients developing to ESRD.
简介:摘要目的分析1个诺里病家系的致病基因变异,确定其遗传学病因。方法对先证者核心家系4名成员的DNA样本进行全外显子组检测,筛选变异位点,确定致病基因。通过Sanger测序对核心家系及7名其他家系成员进行验证。结果全外显子组检测及Sanger测序结果显示先证者及另外3例男性患者的NDP基因均存在c.361C>T(p.Arg121Trp)半合子错义变异,先证者母亲、外祖母和2个表妹均为c.361C>T杂合变异携带者,正常表型男性家系成员均未检测到该变异,符合X连锁隐性遗传病的特点。结论NDP基因c.361C>T错义变异是该诺里病家系的遗传学病因。
简介:AbstractBackground:Developing effective spinal cord repair strategies for spinal cord injury (SCI) is of great importance. Emerging evidence suggests that microRNAs (miRNAs) are closely linked to SCI recovery. This study aimed to investigate the function of miR-34c in the neuronal recovery in rats with SCI.Methods:A rat model with SCI was established. Differentially expressed miRNAs were identified by a microarray analysis. MiR-34c expression in rats was measured by reverse transcription quantitative polymerase chain reaction. Altered expression of miR-34c or C-X-C motif ligand 14 (CXCL14) was introduced in SCI rats to measure their roles in neuronal recovery. Western blot analysis was performed to determine the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription-3 (STAT3). Neuronal apoptosis in rat spinal cord tissues was detected. The concentrations of SCI recovery-related proteins thyrotropin releasing hormone (TRH), prostacyclin (PGI2), and ganglioside (GM) were evaluated by enzyme-linked immunosorbent assay. Data were analyzed using a t-test with a one-way or two-way analysis of variance.Results:Rats with SCI presented decreased grip strength (112.03 ± 10.64 vs. 17.32 ± 1.49 g, P < 0.01), decreased miR-34c expression (7 days: 3.78 ± 0.44 vs. 0.95 ± 0.10, P < 0.05), and increased CXCL14 expression (7 days: 0.61 ± 0.06 vs. 2.91 ± 0.27, P < 0.01). MiR-34c was found to directly bind to CXCL14. Overexpression of miR-34c increased grip strength (11.23 ± 1.08 vs. 31.26 ± 2.99 g, P < 0.01) and reduced neuronal apoptosis in spinal cord tissues (53.61% ± 6.07% vs. 24.59% ± 3.32%, P < 0.01), and silencing of CXCL14 also increased the grip strength (12.76 ± 1.13 vs. 29.77 ± 2.75 g, P < 0.01) and reduced apoptosis in spinal cord tissues (55.74% ± 6.24% vs. 26.75% ± 2.84%, P < 0.01). In addition, miR-34c upregulation or CXCL14 downregulation increased the concentrations of TRH, PGI2, and GM, and reduced phosphorylation of JAK2 and STAT3 in rats with SCI (all P < 0.01).Conclusion:The study provided evidence that miR-34c could promote neuronal recovery in rats with SCI through inhibiting CXCL14 expression and inactivating the JAK2/STAT3 pathway. This study may offer new insights into SCI treatment.
简介:摘要目的旨在探讨C3a-C3a受体(C3aR)在常染色体显性多囊肾病(ADPKD)进展中的作用及机制。方法收集ADPKD患者切除肾组织和PKD1敲除小鼠多囊肾组织,观察C3a、C3aR及F4/80在肾组织中的表达;利用脂多糖(LPS)和白细胞介素4(IL-4)分别刺激巨噬细胞,检测各组细胞C3aR、TNF-α、分型标志物和相关信号通路的表达及机制;使用C3aR抑制剂SB290157(1 mg/kg)处理PKD1敲除小鼠,观察肾脏病理、囊肿相关指标和肾功能变化。结果C3a及C3aR在ADPKD患者和PKD1敲除小鼠肾组织中表达显著上调(均P<0.05),C3aR与F4/80共定位于小鼠多囊肾组织中的巨噬细胞上。体外培养M1型巨噬细胞C3aR表达显著上调(P<0.05),C3a刺激后M1型巨噬细胞表达iNOS、TNF-α和IL-6 mRNA显著上调(均P<0.05),分泌TNF-α增多,说明C3a不仅影响M1型巨噬细胞自身炎性因子表达,还影响其周围炎症微环境;此外,C3a激活M1型巨噬细胞Akt信号通路显著上调(P<0.05)。与模型对照组比较,SB290157治疗组小鼠血Scr、BUN水平、囊肿指数、双肾重/体重(2KW/BW)均显著降低(均P<0.05),小鼠肾组织中C3a、C3aR水平及p-ERK、p-P65通路蛋白表达显著下调(均P<0.05)。结论多囊肾组织中增多的C3a通过C3aR引起巨噬细胞浸润和活化,进而促进ADPKD进展,其机制可能通过Akt活化、TNF-α产生增多所致。C3aR拮抗剂是治疗ADPKD的一个潜在研究方向。
简介:摘要目的用生物信息学分析筛选骨肉瘤预后相关基因。方法从Gene Expression Omnibus(GEO)下载GSE33382、GSE21257数据集。分析获得差异表达基因(DEGs)。对差异基因进行GO分析,构建蛋白互作网络。Cytoscape进一步筛选关键基因,对关键基因进行生存相关性分析。用临床样本验证关键基因与患者预后情况。两组间差异采用Student’s t检验。结果筛选下调基因43个,上调基因43个,GO分析发现差异基因主要富集在免疫应答、抗原处理和呈递、免疫反应、蛋白质加工和成熟等免疫相关过程。在分子功能中,主要参与细胞内主要组织相容性复合体(MHC)Ⅱ类受体活性、核糖体结构组成、信号和分子转导活性等。在细胞组成成分方面,主要与主要组织相容性复合体蛋白质复合物、裂解空泡、液泡、溶酶体、细胞膜、核糖体等细胞器的功能有关。筛选出10个关键基因:补体C1q A链(CIQA)、补体C1q B链(C1QB)、补体C1q C链(C1QC)、单核细胞分化抗原CD 14(CD14)、单核细胞分化抗原CD 74(CD74)、IgE受体Fc片段(FCER1G)、纤维蛋白原样蛋白2(FGL2)、组织相容性抗原(HLA-DRA)、整合素β2亚基(ITGB2)、酪氨酸激酶结合蛋白(TYROBP)。生存分析发现C1QC与骨肉瘤患者生存呈明显负相关。临床样本证实C1QC与肿瘤Enneking分期、转移显著相关(χ2=4.288和9.809,P<0.05),与患者生存时间呈明显负相关(χ2=5.175,P<0.05)。结论生物信息学分析是有效的筛查方法,C1QC是骨肉瘤预后相关因子。
简介:AbstractBackground:We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice.Methods:Intestinal epithelial CCL7 overexpression (CCL7tgIEC) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing.Results:We found that the CCL7tgIEC mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT. Furthermore, HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis.Conclusions:Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.
简介:摘要目的利用条件性重编程细胞(CRC)技术培养人源性前列腺癌细胞,为前列腺癌体外实验研究建立个体化原代细胞库。方法2019年1—4月共获取3例新鲜的前列腺癌病理组织标本,将标本分为2份,一份经术中快速冰冻病理检查确定为癌组织;另一份用0.25% EDTA酶消化为分散的悬浮单个的癌细胞,利用CRC技术对癌细胞进行培养。培养方法:将原代细胞与经30 Gy照射的3T3-J2小鼠成纤维细胞共培养于条件性培养基中,观察癌细胞克隆团生长情况。使用差异性消化对原代细胞进行传代:先用0.25% EDTA胰酶消化1 min去除饲养层细胞,PBS清洗后再用0.25% EDTA胰酶消化原代细胞。待癌细胞稳定后,通过免疫荧光、免疫组化染色、免疫印迹和荧光原位杂交技术等实验,验证所培养的癌细胞性质。结果体外利用CRC技术建立3例前列腺癌原代细胞株,细胞培养约15 d建系成功,并可持续稳定传代。细胞鉴定结果显示,所培养的细胞均表达AR、CK5、CK18和P504s,同时也弱表达PSA。荧光原位杂交技术显示细胞出现≥1.6%的TMPRSS2/ERG基因融合,这些现象符合前列腺癌的细胞特征。结论利用CRC技术能稳定地体外持续培养前列腺癌原代细胞。
简介:摘要目的评价髂静脉球囊扩张治疗对C3以上的浅静脉曲张患者临床症状的改善程度。方法选取新疆医科大学第一附属医院2016年6月至2018年6月收治的C3以上浅静脉曲张患者568例,按治疗方式分为介入球囊扩张组、弹力袜治疗组和剥脱手术组,使用静脉临床严重程度评分(VCSS)评价患者疗效。结果介入球囊扩张组47例,有效40例,无效7例;弹力袜治疗组82例,有效39例,无效43例;剥脱手术组439例,有效280例,无效159例。三组有效率比较差异有统计学意义(P<0.05),介入球囊扩张组症状改善程度高于其他两组(P<0.05)。结论球囊扩张髂静脉可以更好地改善部分C3以上浅静脉曲张患者的临床症状。
简介:摘要目的探讨非高密度脂蛋白胆固醇(non-HDL-C)和高密度脂蛋白胆固醇(HDL-C)比值与海勤官兵亚临床动脉粥样硬化(SA)的相关性及其临床意义。方法回顾性分析陆军厦门特勤疗养中心2015年6月至2018年6月118例SA海勤官兵(SA组)的病例资料,按照颈动脉内中膜厚度(C-IMT)和斑块的发生情况分为增厚组(n=60例)和斑块组(n=58例);以同期入院疗养且体检健康的海勤官兵60例为对照组。比较各组间常规体检参数包括临床资料参数如心血管健康行为因素评分、C-IMT和血糖,以及血脂参数如三酰甘油(TG)、总胆固醇(TC)、HDL-C、低密度脂蛋白胆固醇(LDL-C)、non-HDL-C、non-HDL-C/HDL-C、血浆致动脉硬化指数(AIP)。对C-IMT和AIP行相关性和多元线性回归分析;对颈动脉斑块发生情况行二元Logstic回归分析。结果方差分析结果显示,对照组、增厚组、斑块组的TG、TC、LDL-C、non-HDL-C、AIP、non-HDL-C/HDL-C、C-IMT均依次显著升高,HDL-C、运动评分、健康饮食评分均依次显著降低(P<0.05或P<0.01)。相关性分析结果显示,non-HDL-C/HDL-C与C-IMT和AIP呈正相关(P<0.05或P<0.01)。回归分析结果显示,non-HDL-C/HDL-C均进入分别以C-IMT和AIP为因变量的回归模型(P<0.01),未进入以颈总动脉斑块为因变量的回归模型(P>0.05)。结论SA海勤官兵存在明显血脂代谢异常。non-HDL-C/HDL-C与C-IMT和AIP呈正相关性,是海勤官兵SA的危险因素,可作为评价海勤官兵SA的良好指标,应在海勤官兵血脂控制中重点关注。
简介:【摘要】 目的 对在 CCU 病房护理中应用优质护理的效果进行探究。 方法 样本取 2018 年 12 月 -2019 年 12 月本院收治的 102 例 CCU 病房患者,随机平均分配为 A 组与 B 组,每组各 51 例。其中 B 组行常规护理, A 组行优质护理。最终统计对比两组患者焦虑自评量表( SAS 评分)、抑郁自评量表( SDS 评分)、护理满意度。 结果 行优质 护理 A 组 CCU 病房患者 SAS 评分和 SDS 评分均 显著低于 B 组, P<0.05 ,有统计学意义; A 组治疗依从性要显著高于 B 组,差异明显, P<0.05 ,有统计学意义。 结论 因此对在 CCU 病房护理中应用优质护理的效果在临床上被证实是非常重要的,有助于缓解重症病人焦虑和抑郁的情绪,树立病情康复的信心,提高治疗和护理依从性,促进疾病的康复,在临床上有广泛推广价值。