Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study

BackgroundMesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated.MethodsFrom March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment.ResultsAt 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed.ConclusionOur results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor     

保留乳房手术对比乳房根治术治疗三阴性乳腺癌疗效的Meta分析

目的评价保留乳房手术(简称保乳术)和乳房根治术对三阴性乳腺癌患者预后的影响。 方法通过PubMed、Embase、MEDLINE、中国知网、维普和万方数据库,收集符合要求的队列研究。由2位评价员按照纳入与排除标准独立筛选文献、提取资料[病例数、生存曲线、风险比(HR)等],并运用改良纽卡斯尔-渥太华量表(NOS)对文章的质量进行系统评价。若文中未提及HR,则运用Engauge Digitizer 6.2软件提取各研究中生存曲线的数据,再计算出乳房根治术和保乳术患者OS率、DFS率以及无局部区域复发生存率(LRRFS)的ln(HR)和se[ln(HR)];若文中提及HR,则直接计算出ln(HR)和se[ln(HR)]。最后统一使用RevMan 5.3软件对研究数据进行Meta分析。 结果最终纳入符合标准的相关文献10篇,累计样本量5 487例患者。NOS评价结果显示,所有纳入文献评分为7～9分,均为质量较高的文献。Meta分析显示,在三阴性乳腺癌的队列研究中,保乳术患者OS率明显高于乳房根治术者(HR＝1.25,95%CI：1.09～1.44,P＝0.001)。而保乳术与乳房根治术相比,患者DFS率和无局部区域复发生存(LRRFS)率的差异均无统计学意义(HR＝0.97,95%CI：0.72～1.30,P＝0.830;HR＝1.11,95%CI：0.93～1.34,P＝0.250)。 结论三阴性乳腺癌患者行保乳术的OS率优于乳房根治术,因此,满足保乳术指征的患者应该尽量选择保乳术。     

MnSOD Val16Ala polymorphism associated with retinopathy risk in diabetes: a PRISMA-compliant Meta-analysis of case-control studies

AIM: To investigate the association of Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Subgroup, sensitivity, and cumulative analyses were performed. Publication bias was also analyzed. RESULTS: Eight studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48-0.91, P<0.0001), this result was demonstrated to be relatively stable in cumulative analysis. No significant publication bias was found. This polymorphism was also associated with the risk of DR in Caucasians under the dominant model (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model (OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention should be paid to carriers of these susceptibility genes.     

多西他赛联合卡培他滨一线治疗转移性乳腺癌的临床疗效和不良反应

目的 探讨多西他赛联合卡培他滨一线治疗转移性乳腺癌的临床疗效及不良反应,并分析其在转移性乳腺癌不同分子分型中的疗效.方法 回顾性分析北京市朝阳区三环肿瘤医院2012年1月1日至2015年12月31日多西他赛联合卡培他滨一线治疗转移性乳腺癌患者108例,可评价病例104例,分析其临床特点及疗效、不良反应等.结果 104例患者分为Luminal型85例,三阴型14例,人类表皮生长因子受体-2(HER-2)过表达型5例.近期疗效:完全缓解(CR)4例,部分缓解(PR)51例,疾病稳定(SD)37例,疾病进展(PD)12例,客观缓解率为52.9％,疾病控制率为88.5％;其中Luminal型CR4例,PR 43例,SD 33例,PD 5例;三阴型PR 6例,SD 3例,PD 5例;HER-2过表达型PR 2例,SD1例,PD 2例,不同分子分型近期疗效比较差异无统计学意义(x2=4.429,P=0.106).104例患者无进展生存期(PFS)为1.5 ～ 121.0个月,中位PFS为10.0个月,其中Luminal型患者的中位PFS为11.0个月,三阴型为4.0个月,HER-2过表达型为10.3个月,差异具有统计学意义(x2=7.510,P=0.006).常见不良反应为手足综合征、恶心或呕吐、粒细胞下降、贫血、腹泻等.2、3级手足综合征发生率为44.2％(46/104),3、4级粒细胞下降发生率为39.4％ (41/104).结论 多西他赛联合卡培他滨一线治疗转移性乳腺癌疗效确切,不良反应可耐受,其中Luminal型获益显著.     

糖尿病神经原膀胱的治疗现状

糖尿病神经原膀胱(DNB)是糖尿病在泌尿系统最主要的并发症,其发病机制复杂,目前尚无特效的治疗方法.营养神经、调节神经递质、抗氧化应激、电刺激、导尿术等单一化学药物或物理治疗常难以达到临床治疗要求,理化联合治疗可协同增加疗效.近年来,干细胞和基因研究的兴起为DNB的治疗提供了新思路,但仍处于实验探索阶段     

The Immunohistochemical Evaluation of Solid Pseudopapillary Tumors of the Pancreas and Pancreatic Neuroendocrine Tumors Reveals ERO1Lβ as a New Biomarker

Solid pseudopapillary tumor of the pancreas (SPTP) is a class of low-grade malignant tumors that carry a favorable prognosis after surgery. Our group has reported that dysfunctions in the endoplasmic reticulum (ER) protein processing pathway may play a role in tumor development. However, alterations of this pathway in other pancreatic tumors had not been well investigated. In this study, we collected 35 SPTP and pancreatic neuroendocrine tumor (PNET) specimens and described the clinicopathological features of them. We performed immunohistochemistry (IHC) for 6 representative proteins (ERO1Lβ, TRAM1, GRP94, BIP, P4HB, and PDIA4) involved in the ER pathway in both SPTP and PNET specimens. We compared the IHC scoring results of tumors and matched normal pancreas tissues and demonstrated that these proteins were downregulated in SPTP specimens. Five of these proteins (TRAM1, GRP94, BIP, P4HB, and PDIA4) did not display significant changes between PNET and normal pancreas tissue. However, ERO1Lβ was upregulated in PNET tissues compared to the normal tissues, which could be used as a pathological biomarker in the future.     

病理高危因素对I期直肠癌患者预后的影响

目的探讨病理高危因素与I期直肠癌预后的关系,从而为临床提供有益的指导。 方法回顾性分析2011年1月至2013年1月期间在哈尔滨医科大学附属第二医院结直肠肿瘤外科接受根治性手术治疗且术后病理回报为I期的直肠癌患者178例,分为有高危因素组和无高危因素组,有高危因素的患者119例,男性60例,女性59例;无高危因素的患者59例,男性33例,女性26例。中位随访时间为33个月,并详细记录患者的无病生存期。 结果2组患者在性别、年龄、大体类型、分化类型、淋巴结检出数目、浸润深度、肿瘤部位等方面比较差异无统计学意义（χ²=0.480,t=2.023,χ²=2.244,χ²=5.614,t=2.387,χ²=1.590,χ²=3.099,P均>0.05）,2组术后随访时间相同,无高危因素组患者预后良好无复发及远处转移,而有高危因素组中出现了局部复发和远处转移的病例。有和无高危因素的I期直肠癌患者的无病生存期差异存在统计学意义（HR=0.86,95%CI 0.56~0.97）。淋巴管浸润、脉管瘤栓、神经侵犯及低分化是影响患者无病生存期的主要因素。 结论对于含有病理高危因素的I期直肠癌患者应进行密切随访观察。     

特发性血小板减少性紫癜患者行腹腔镜乙状结肠癌切除术一例的护理

总结1例特发性血小板减少性紫癜患者行腹腔镜乙状结肠癌切除术的护理。其护理要点包括：做好心理支持,全方位呼吸道管理、有效的预防感染和出血护理,做好用药指导。经过有效的诊治和精心的护理,患者于术后第7天出院。     

路志正调理脾胃治疗胸痹的学术思想浅析

全国著名中医学家路志正教授精通中医典籍,对脾胃学说的研究造诣尤深,行医60余年,形成一套独特的临床经验.路老师善用调理脾胃治疗多种疑难杂症,其中运用调理脾胃法辨治胸痹是其学术思想和临床经验的组成部分.现就笔者学习心得简介如下.     

Synthesis and biological evaluation of 68Ga-bis-DOTA-PA as a potential agent for positron emission tomography imaging of necrosis

IntroductionNecrosis is a form of cell death that occurs in a variety of pathological conditions but can also be the result of therapy in cancer treatment. A radiotracer that could image necrotic cell death using PET could therefore be a useful tool to provide relevant information on the disease activity or therapeutic efficacy and assist in diagnosis and therapy management of several disorders. Pamoic acid derivatives have previously been reported to show a selective uptake in tissue undergoing cellular death via necrosis. In this study 4,4′-methylene-bis(2-hydroxy-3-naphthoic hydrazide) (pamoic acid bis-hydrazide) was conjugated to the macrocyclic ligand DOTA and labeled with the generator produced positron emitter ⁶⁸Ga. The resulting complex (⁶⁸Ga-bis-DOTA-PA; ⁶⁸Ga-3) was evaluated as a potential radiotracer for imaging tissues undergoing cellular death via necrosis.MethodsBis-DOTA-PA was synthesized and labeled with ⁶⁸Ga. Biodistribution of ⁶⁸Ga-3 and analysis of plasma were studied in normal NMRI mice. Binding of the complex to necrotic tissue was first evaluated by in vitro autoradiography. Further evaluation of the uptake in necrotic tissue was performed in two different models of necrosis using microPET imaging in correlation with ex vivo autoradiography, biodistribution studies and histochemical staining. A biodistribution study in a mouse model of hepatic apoptosis was performed to study the selectivity of the uptake of ⁶⁸Ga-bis-DOTA-PA in necrotic tissue.Results⁶⁸Ga-3 was obtained with a decay-corrected radiochemical yield of 51.8% ± 5.4% and a specific activity of about 12 GBq/μmol. In normal mice, the complex was slowly cleared from blood, mainly through the renal pathway, and showed high in vivo stability. ⁶⁸Ga-bis-DOTA-PA displayed high and selective uptake in necrotic tissue and allowed imaging of necrotic tissue using microPET.Conclusion⁶⁸Ga-3 was synthesized and characterized. In vitro, in vivo and ex vivo studies showed that the complex displays high and selective uptake in tissue undergoing cellular death via necrosis.