BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.

背景与目标： : 在四个患有扁平耳蜗听力损失的听众和四个年龄匹配的正常听力听众中，测量了固定和幅度调制的噪声masker的辅音识别。掩蔽器调制速率在2和128Hz之间系统地变化。在所有正常听力的听众中，掩蔽释放 (MR) 在波动中比在固定噪声中更好的识别性能，在8-16Hz波动的掩蔽器中最高。相比之下，仅在四个受损听众中的两个中观察到MR。在这些听众中，MR比正常人差，并且以较低的速率 (即2或8Hz) 达到峰值。MR对应于所有正常听力的听众在2到64Hz之间的发声，位置和方式的信息接收增加。在受损的听众中，主要观察到方式的信息接收增加，而地点的信息接收则主要减少，但这些差异并不显着。对于所有语音特征，与正常听力的听众相比，以较低的掩蔽率 (<或 = 32Hz) 观察到MR。因此，这项研究表明，耳蜗损伤在定量和定性上都会影响MR。

BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.

背景与目标： : 野生型 (WT) 序列p53肽是广泛适用的癌症疫苗的有吸引力的候选者。这项研究的目的是评估WT p53-based免疫治疗方法对肝细胞癌 (HCC) 患者的潜力。通过在24例HCC患者中使用肽/HLA-A2.1四聚体，在外周血中直接鉴定了对WT p53(149-157) 和WT p53(264-272) hla-a * 0201限制性表位特异性的循环CD8 + T细胞。使用定量实时聚合酶链反应测定法，通过分析颗粒酶B和干扰素-γ mRNA转录来评估WT p53肽特异性刺激后的细胞毒性T淋巴细胞 (CTL) 活性。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中的p53状态，主要组织相容性复合物 (MHC) 和共刺激分子的表达。与健康对照组相比，HCC患者表现出明显更高的WT p53-specific记忆CD8 + T细胞频率和更强的WT p53-specific CTL活性。p53-specific CD8 + T细胞的频率增加及其活性与肿瘤细胞的选择性HLA-A2等位基因丢失和共刺激分子表达降低相关。此外，p53-specific T细胞数量的增加与肿瘤细胞中高MHC II类表达相吻合，但与肿瘤淋巴结转移分期系统的T状态成反比。我们的结果表明存在自然免疫监视和肿瘤免疫逃避，涉及HCC患者针对WT p53肿瘤抗原的T细胞反应。这些发现可能对癌症疫苗的未来发展具有重要意义。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A 29-year-old man was admitted to our institution 10 days after he had undergone an urgent exploratory laparotomy at a local army hospital after a terrorist bombing attack. On admission, deep second-degree and third-degree burns involving 25% of the upper and lower extremities were present, together with a 25 x 10-cm abdominal full-thickness blast injury defect on the left side, an infected eviscerated midline incision, and a colostomy on the right side of the abdomen. The patient underwent a second laparotomy, at which time the intraabdominal abscess was drained, and the abdominal cavity was irrigated with saline. A jejunal perforation was found and sutured. The abdominal cavity was left open and covered with a Bogota bag for temporary closure. On postburn day 18, the patient underwent débridment and grafting of the third-degree burns to the left and right arm and right lower extremities. After several débridment sessions (postburn days 16, 18, 20, 22, and 24), an abdominal skin release and reapproximation were performed (postburn day 26). On postburn day 36, split-thickness skin grafts were placed directly on the granulated tissue of the intestines and on a defect in the left flank and iliac regions. Postoperatively, the patient did well. He was discharged on postburn day 78 with all wounds well healed. In our opinion, temporary closure followed by direct application of meshed split-thickness skin grafts to exposed abdominal viscera represents a simple method of reconstruction that can be safely performed, with minimal risk, on critically ill patients.

背景与目标： : 一名29岁的男子在恐怖爆炸袭击后在当地一家军队医院接受紧急剖腹探查术10天后被送入我们的机构。入院时，出现了涉及上下肢25% 的深二度和三度烧伤，左侧有25x10 cm的腹部全层爆炸伤缺损，感染的内脏中线切口，以及腹部右侧的结肠造口术。患者接受了第二次剖腹手术，此时引流了腹腔内脓肿，并用盐水冲洗了腹腔。发现空肠穿孔并缝合。腹腔保持开放状态，并用波哥大袋覆盖，以暂时关闭。在烧伤后第18天，患者接受了三度烧伤的移植，并将其移植到左，右臂和右下肢。经过几次缓解 (烧伤后第16、18、20、22和24天) 后，进行了腹部皮肤释放和重新逼近 (烧伤后第26天)。在烧伤后的第36天，将厚度分开的皮肤移植物直接放置在肠的颗粒状组织以及左侧和ili区的缺损处。术后，患者表现良好。他在烧伤后第78天出院，所有伤口均愈合良好。在我们看来，暂时封闭，然后直接将网状厚度的皮肤移植物应用到暴露的腹部内脏上，代表了一种简单的重建方法，可以对危重病人安全地进行，风险最小。

BACKGROUND & AIMS: AIM:To determine the knowledge, attitudes and practice of women living in peri-urban settlements with regard to screening for cervical cancer. METHOD:A community-based questionnaire survey of 165 women living in a defined area of Khayelitsha, a peri-urban settlement on the outskirts of Cape Town. RESULTS:Two hundred households were visited, with a response rate of 84%. Median age of respondents was 27.5 years. The majority of interviewees were married (53.3%), unemployed (61.5%), had an educational status of standard 4 or less (58.1%) and had been living in Cape Town for 4 years or more (64.3%). The median parity was 2 (range 0-11). Most interviewees were currently using contraception (52.4%). One-third (35.4%; 95% CI 28.1-42.7%) of interviewees had heard of the Pap smear. Of these women, most had obtained their information from the midwife obstetric unit (MOU), and this was the most commonly reported facility where Pap tests were known to be done. The majority of interviewees did not regard the test (or the prospect thereof) as embarrassing (88.4%), painful (89.1%) or harmful (90.9%), and indicated that they would have the test done (89.1%). The most important reason for choice of where the test should be done was proximity to place of residence (83.9%). More than one-third of interviewees reported having had a Pap test (37.2%; 95% CI 28.8-44.8%). The most common reason for not having had a test was that the interviewee had never heard of it (81.3%). Most had undergone the test at a MOU (65.6%), where it had been part of an antenatal work-up (80.3%). Fewer than half of the interviewees who had undergone a test knew the result of their test. CONCLUSION:The antenatal, obstetric and family planning services in the area have been effective, to a limited extent, in providing information and conducting screening. However, these services are missing many opportunities to fulfill this function, and knowledge and practice of cervical cytology screening in this community are poor. With the implementation of a rational policy for screening in this area there is the potential to achieve good coverage.

背景与目标：

BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.

背景与目标： : 肿瘤浸润的基质细胞 (TISC) 以及肿瘤本身被认为与肿瘤相关的免疫抑制有关，这是肿瘤逃避免疫监视的关键机制之一。然而，由于TISC在已建立的肿瘤中的比例较小，因此很难制备TISC。因此，被认为与肿瘤相关的免疫抑制有关的细胞通常是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中，我们开发了一种从已建立的肿瘤中直接制备TISC的方法，以分析其功能。使用绿色荧光蛋白 (GFP) 转基因 (Tg) 小鼠和C57BL/6小鼠移植了GFPTg小鼠的骨髓 (BM) 细胞，我们检测到了TISC的三个亚群: 一个与BM衍生的未成熟髓样细胞 (ImC) 相容，另外两个亚群，CD11b(+) 细胞和CD11b(-) 细胞不起源于BM。在gm-csf存在下用肿瘤培养后，包括这些亚群但不是每个亚群的TISC可以抑制anti-CD3诱导的T细胞增殖。在我们的系统中，肿瘤没有直接抑制T细胞反应，但是肿瘤的未知因素会影响TISC的免疫抑制。

BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标：

BACKGROUND & AIMS: :Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.

背景与目标： : 在过去的十年中，骨髓含有内皮细胞前体的旧观念已成为人们重新关注的领域。尽管有些人仍然认为血液中没有内皮前体，即使在那些内皮前体中也是如此，但对于它们是什么或它们做什么还没有共识。在这篇综述中，我们描述了鉴定内皮细胞的问题，并得出结论，内皮一氧化氮合酶的表达可能是表型最可靠的抗原指标。还提供了两种不同类型的内皮前体的证据。我们建议，尽管没有单个内皮细胞前体，但我们可能能够利用这些表型变异来更好地了解它们的生物学。我们还讨论了各种遗传，表观遗传和方法上的差异如何解释关于骨髓来源的前体在正常血管维持和对损伤的反应中的生理相关性的看似矛盾的发现。还提供了有关肿瘤类型和位置对骨髓来源细胞对肿瘤脉管系统贡献的影响的数据。这些数据提供了希望，我们最终可能能够预测那些骨髓来源的细胞将在其中做出重大贡献的肿瘤，并相应地设计治疗方法。最后，开始确定调节骨髓细胞对内皮的募集和功能的因素，并讨论了其中的几种因素，包括基质衍生因子1，单核细胞趋化因子1和血管内皮生长因子。

BACKGROUND & AIMS: BACKGROUND:Trabecular bone strength diminishes as a result of osteoporosis and altered biomechanical loading at the vertebral and spinal levels. The spine consists of the anterior, middle and posterior columns and the load supported by the anterior and middle columns will differ across different regions of the spine. Stress shielding of the anterior column can contribute to bone loss and increase the risk of wedge fracture. There is a lack of quantitative data related to regional spinal bone mineral density distribution over time. We hypothesize that there is an increase in the posterior-to-anterior vertebral body bone mineral density ratio and a decrease in whole-body bone mineral density over time. METHODS:Bone mineral density was measured in 33 subjects using quantitative computed tomography scans for L1-L3 vertebrae, region (anterior and posterior vertebral body), and time (baseline and 6 years after). FINDINGS:Lumbar bone mineral density decreased significantly (Δ: ~15%) from baseline to the 6th year visit. Individual vertebra differences over time (L1: ~14%, L2: ~14%, L3: ~17%) showed statistical significance. Anterior bone mineral density change was significantly greater than in the posterior vertebral body region (Δ anterior: ~18%; Δ posterior: ~13%). Posterior-to-anterior bone mineral density ratio was significantly greater in the 6th year compared to baseline values (mean (SD), 1.33 (0.2) vs. 1.23 (0.1)). INTERPRETATION:This study provides longitudinal quantitative measurement of bone mineral density in vertebrae as well as regional changes in the anterior and posterior regions. Understanding bone mineral density distribution over time may help to decrease the risk of wedge fractures if interventions can be developed to bring spine loading to its normal state.

背景与目标：

BACKGROUND & AIMS: :Immediate placement refers to the placement of an implant into a tooth socket at the time of extraction; early placement refers to the placement of an implant after substantial gingival healing, but before any clinically significant bone fill occurs within the socket. This study evaluated the success and survival rates of implants following immediate and early placement. 50 implants were placed in 36 patients. 26 immediate (group I) and 24 early placements (group II) were performed. Pain or tenderness with function, mobility, radiographic bone loss from initial surgery and exudate history were evaluated. Mean vertical bone loss in the immediate placement group was 0.55 mm and 0.80 mm in the early placement group. The survival rate for the immediate placement group was 96.16% with 51.6 months follow-up and in the early placement group was 100% with 61.9 months follow-up. The results of this study suggest that although the success and survival rates of early placed implants were a little higher and the follow up period was longer than immediately placed implants, the difference was not remarkable. In conclusion, both implant insertion techniques are safe and reliable procedures with considerably high survival rates.

背景与目标： : 立即放置是指在拔牙时将植入物放置在牙槽中; 早期放置是指在牙龈实质性愈合后但在牙槽内发生任何临床上重要的骨填充之前放置植入物。这项研究评估了立即和早期放置后植入物的成功率和存活率。在36例患者中放置了50个植入物。进行了26次即时放置 (I组) 和24次早期放置 (II组)。评估了疼痛或压痛的功能，活动度，初始手术引起的影像学骨丢失和渗出史。立即放置组的平均垂直骨丢失是0.55毫米的，而早期放置组的平均垂直骨丢失是0.80毫米的。立即放置组的生存率96.16% 为51.6个月的随访，而早期放置组的生存率100% 为61.9个月的随访。这项研究的结果表明，尽管早期放置的植入物的成功率和存活率比立即放置的植入物高一些，并且随访时间更长，但差异并不显着。总之，两种植入物插入技术都是安全可靠的程序，存活率很高。

BACKGROUND & AIMS: BACKGROUND:This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders. METHODS:Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFα levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI. RESULTS:Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9-11.2, p < 0.001). CONCLUSION:Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on the healing of bone defects in rats with streptozotocin (STZ)-induced DM. METHODS:28 male Sprague-Dawley rats were used in this study. 14 animals received a single dose of STZ intraperitoneally (65 mg/kg) to induce Type I DM, whereas others were injected only with sterile saline solution. Four weeks later, standard bone defects were created in the tibiae of rats. Surgical wounds in one group from each of the diabetic and non-diabetic animals were irradiated with diode laser for every other day for 4 weeks and they were described as DM + LLLT and CONT + LLLT groups, respectively. Remaining two groups received no laser treatment. New bone formation, osteoblast and blood vessel counts were calculated in histologic sections. RESULTS:DM group had significantly smaller bone area and lower blood vessel count when compared to DM + LLLT, CONT and CONT + LLLT groups (p < 0.05 for each). CONT and CONT + LLLT groups had significantly larger bone area than DM + LLLT group (p < 0.05 for both). CONCLUSIONS:LLLT application promoted vascularization and new bone formation in animals with DM to a limited extent, since it was unable to support the healing process up to the level of non-diabetic animals.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. METHODS:Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses. RESULTS:After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate<0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors. CONCLUSION:Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Monochorionic (MC) twins are at increased risk of early fetal loss secondary to vascular complications such as twin-twin transfusion syndrome (TTTS). This study compared the early perinatal loss rates between MC and dichorionic (DC) twins in an era of invasive treatment for TTTS. METHODS:This was a retrospective study of all twin pregnancies of known chorionicity from a large regional cohort of nine hospitals over a 10-year period. Ultrasound data were matched to hospital delivery records and to a mandatory national register of pregnancy losses. Prospective risk of pregnancy loss from 14 to 24 weeks' gestation was calculated and the survival trend of MC and DC twins was analyzed using Kaplan-Meier survival analysis. RESULTS:The analysis included 3117 twin pregnancies (605 MC and 2512 DC). The total risk of early pregnancy loss (miscarriage and neonatal death) before 24 weeks was significantly higher in MC twins (60.3 per 1000 fetuses) than in DC twins (6.6 per 1000 fetuses), with a relative risk of 9.18 (95% CI, 6.0-13.9). Survival analysis showed a significant difference in overall and early mortality between MC and DC twins (log-rank test, P < 0.0001), while no difference was noted after 24 weeks' gestation (log-rank test, P = 0.08). CONCLUSIONS:Early pregnancy loss is significantly more common in MC than in DC twins, but no difference in the prospective risk of mortality between MC and DC twins is evident after 24 weeks' gestation. The observed early mortality rate has almost halved in comparison with previous studies in the published literature. Early detection and prompt treatment of complications in MC twins are likely to have contributed to this improvement in outcome.

背景与目标：

BACKGROUND & AIMS: :Electrical fields are known to interact with human cells. This principle has been explored to regulate cellular activities for bone tissue regeneration. In this work, Saos-2 cells were cultured on conductive scaffolds made of biodegradable poly(L-lactide) and the heparin-containing, electrically conducting polypyrrole (PPy/HE) to study their reaction to electrical stimulation (ES) mediated through such scaffolds. Both the duration and intensity of ES enhanced cell proliferation, generating a unique electrical intensity and temporal "window" within which osteoblast proliferation was upmodulated in contrast to the downmodulation or ineffectiveness in other ES regions. The favourable ES intensity (200 mV/mm) was further investigated in terms of the gene activation and protein production of two important osteoblast markers characterised by extracellular matrix maturation and mineralisation, that is alkaline phosphatase (ALP) and osteocalcin (OC). Both genes were found activated and the relevant protein production increased significantly following ES. In contrast, ES in the down-modulation region (400 mV/mm) suppressed the production of both ALP and OC. This work demonstrated that important osteoblast markers can be modulated with specific ES parameters mediated through conductive polymer substrates, providing a unique strategy for bone tissue engineering.

背景与目标： 已知电场与人类细胞相互作用。已探索此原理来调节骨组织再生的细胞活性。在这项工作中，将Saos-2细胞培养在由可生物降解的聚 (L-丙交酯) 和含肝素的导电聚吡咯 (PPy/HE) 制成的导电支架上，以研究它们对通过此类支架介导的电刺激 (ES) 的反应。ES的持续时间和强度都增强了细胞增殖，产生了独特的电强度和时间 “窗口”，与其他ES区域的下调或无效相反，在该窗口内对成骨细胞增殖进行了上调。进一步研究了有利的ES强度 (200  mV/mm)，即两种重要的成骨细胞标志物的基因活化和蛋白质生产，其特征是细胞外基质成熟和矿化，即碱性磷酸酶 (ALP) 和骨钙素 (OC)。发现两个基因都被激活，并且在ES之后相关的蛋白质产量显着增加。相反，下调制区域 (400  mV/mm) 中的ES抑制了ALP和OC的产生。这项工作表明，重要的成骨细胞标志物可以通过导电聚合物底物介导的特定ES参数进行调节，为骨组织工程提供了独特的策略。