Intrathecal catheterisation after observed accidental dural puncture in labouring women: update of a meta-analysis and a trial-sequential analysis

BackgroundOur meta-analysis from 2013 showed that inserting a catheter intrathecally after an observed accidental dural puncture can reduce the need for epidural blood patch in labouring women requesting epidural analgesia. We updated our conventional meta-analysis and added a trial-sequential analysis (TSA).MethodsA systematic literature search was conducted to identify studies that compared inserting the catheter intrathecally with an epidural catheter re-site or with no intervention. The extracted data were pooled and the risk ratio (RR) and 95% confidence interval (95%CI) for the incidence of post-dural puncture headache (PDPH) was calculated, using the random effects model. A contour-enhanced funnel plot was constructed. A TSA was performed and the cumulative Z score, monitoring and futility boundaries were constructed.ResultsOur search identified 13 studies, reporting on 1653 patients, with a low risk of bias. The RR for the incidence of PDPH was 0.82 (95%CI 0.71 to 0.95) and the RR for the need for epidural blood patch was 0.62 (95%CI 0.49 to 0.79); heterogeneity of both analyses was high. The TSA showed that the monitoring or futility boundaries were not crossed, indicating insufficient data to exclude a type I error of statistical analysis. Contour-enhanced funnel plots were symmetric, suggesting no publication bias.ConclusionsConventional meta-analyses showed for the first time that intrathecal catheterisation can reduce the incidence of PDPH. However, TSA did not corroborate this finding. Despite increasing use in clinical practice there is no firm evidence on which to base a definite conclusion.     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

早期十全大补汤联合肠内营养乳剂治疗胃癌术后(气血两虚证)喂养不耐受临床评价

目的探讨早期使用十全大补汤联合肠内营养乳剂(TP)治疗胃癌术后(气血两虚证)发生喂养不耐受(FI)的影响因素及对营养指标、中医证候积分的影响。方法回顾性分析术后早期行十全大补汤联合TP治疗的80例胃癌术后(气血两虚)患者的病历资料,根据是否出现FI分为耐受组(34例)和不耐受组(46例)。FI的相关影响因素进行单因素及多因素分析,并观察FI对患者营养指标、中医证候积分的影响。结果单因素分析显示,患者术后第1天下床活动时间、开始肠内营养(EN)的时间、使用营养泵、早期灌肠与FI的发生密切相关(P <0. 05);多因素Logistic回归分析显示,患者第1天下床活动时间≥2 h[OR=0. 022,P=0. 001,95%CI(0. 002,0. 223)]、使用营养泵[OR=0. 021,P=0. 000,95%CI(0. 003,0. 162)]是FI发生的独立危险因素;术后10 d,耐受组患者白蛋白(ALB)、血红蛋白(Hb)升高水平优于不耐受组(P <0. 05),中医证候积分显著低于不耐受组(P <0. 05)。结论胃癌术后(气血两虚证)患者早期给予十全大补汤联合TP治疗开始后,患者第1天下床活动时间不短于2 h、使用营养泵能有效减少FI的发生,并改善了患者的营养状态,减轻了中医临床症状。     

TLR9在不同胎龄新生儿脐血中的表达变化

目的 通过观察早产儿不同胎龄Toll样受体9（TLR9）的表达，探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份，按胎龄分为4组，28~31周组，31~34周组，34~37周组，≥37周组，采用流式细胞术和实时荧光定量PCR方法，分别检测其TLR9的蛋白和mRNA表达情况，了解其与胎龄之间的关系，并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组，31~34周组，34~37周组，≥37周组分别为（15.93±6.23）%，（11.63±6.70）%，（13.66±6.88）%，（20.51±12.06）%；其在胎龄28~31周较高，至31~34周逐渐下降至最低，两组差异有统计学意义（P<0.05）；34~37周后TLR9阳性细胞率表达逐渐升高，至≥37周达最高，两胎龄组比较，差异具有统计学意义（P<0.05）。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关（r=0.273，P=0.006）。TLR9 mRNA表达在28~31周组，31~34周组，34~37周组，≥37周组分别为（4.95±3.44）%，（8.89±8.49）%，（13.91±10.92）%，（7.19±7.11）%；其在28~36周逐渐升高，与胎龄呈正相关（r=0.355，P< 0.001）。≥37周TLR9 mRNA表达量下降，该值虽高于28~31周，但差异无统计学意义（P>0.05）。相关性分析表明，同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关（r=-0.227，P=0.011）。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异，TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加，TLR9 mRNA在28~36周间随着胎龄的增加而增加。     

低密度脂蛋白在2型糖尿病骨质疏松中的作用研究进展

2型糖尿病及骨质疏松已成为我国最主要的慢性代谢性疾病。2型糖尿病常伴有血脂紊乱，常表现为低密度脂蛋白升高，而越来越多的研究表明血脂通过不同的方式影响骨代谢，其机制可能是通过抑制骨髓间充质干细胞成骨分化，通过RANK/RNAKL/OPG信号通路及炎症反应调节破骨细胞等方式调节骨代谢。     

Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells

Neural crest stem cells (NCSCs), a population of multipotent cells that migrate extensively and give rise to diverse derivatives, including peripheral and enteric neurons and glia, craniofacial cartilage and bone, melanocytes and smooth muscle, have great potential for regenerative medicine. Non-human primates provide optimal models for the development of stem cell therapies. Here, we describe the first derivation of NCSCs from cynomolgus monkey embryonic stem cells (CmESCs) at the neural rosette stage. CmESC-derived neurospheres replated on polyornithine/laminin-coated dishes migrated onto the substrate and showed characteristic expression of NCSC markers, including Sox10, AP2α, Slug, Nestin, p75, and HNK1. CmNCSCs were capable of propagating in an undifferentiated state in vitro as adherent or suspension cultures, and could be subsequently induced to differentiate towards peripheral nervous system lineages (peripheral sympathetic neurons, sensory neurons, and Schwann cells) and mesenchymal lineages (osteoblasts, adipocytes, chondrocytes, and smooth muscle cells). CmNCSCs transplanted into developing chick embryos or fetal brains of cynomolgus macaques survived, migrated, and differentiated into progeny consistent with a neural crest identity. Our studies demonstrate that CmNCSCs offer a new tool for investigating neural crest development and neural crest-associated human disease and suggest that this non-human primate model may facilitate tissue engineering and regenerative medicine efforts.     

益气通脉饮联合西药治疗气虚血瘀型冠心病心绞痛90例临床疗效观察

目的:探讨益气通脉饮治疗气虚血瘀型冠心病心绞痛的临床疗效。方法:选取2017年10月—2019年2月烟台业达医院收治的气虚血瘀型冠心病心绞痛的患者90例作为研究对象,根据随机数字表法将所选患者均分为两组,每组各45例,两组的一般资料经统计学方法,差异无统计学意义(P>0.05),因此具有可比性。对照组给予常规西药进行治疗,观察组在对照组治疗基础上给予益气通脉饮治疗,1个月后比较两组临床的疗效,评估治疗前后中医证候、心绞痛症状分级和血脂水平。临床检测的数据通过统计产品与服务解决方案(Statistical Product and Service Solutions,SPSS) 19.0软件进行分析和处理,计量的数据使用平均数±标准差(x±s)表示,采用双侧t检验,计数的数据采用χ~2检验,以%表示,以P<0.05为差异有统计学意义。结果:治疗后,对照组和观察组都有一定疗效,但观察组的改善中医证候总有效率95.56%(43/45),高于对照组的82.22%(37/45),两组比较具有统计学意义(P<0.05);心绞痛的症状总有效率观察组为93.33%(42/45),对照组为77.78%(35/45),两组比较差异有统计学意义(P<0.05);与治疗前相比较,两组治疗后的三酰甘油(Triglyceride,TG)、血清总胆固醇(Serum Total Cholesterol,TC)、高密度脂蛋白胆固醇(High Density Liptein Cholesterol,HDL-C)水平均降低(P<0.05),且观察组治疗后低于对照组(P<0.05),两组治疗后的HDL-C升高(P<0.05),组间比较,差异无统计学意义(P>0.05)。结论:益气通脉饮治疗气虚血瘀型冠心病心绞痛的疗效显著,值得临床进一步研究与推广应用。     

Macroporous thin membranes for cell transplant in regenerative medicine

The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress–strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding.