经椎间孔入路经皮内窥镜下椎间盘切除术治疗钙化型腰椎椎间盘突出症

目的探讨经椎间孔入路经皮内窥镜下椎间盘切除术(PETD)治疗钙化型腰椎椎间盘突出症的临床疗效。方法回顾性分析本院2013年9月—2014年9月收治的20例钙化型腰椎椎间盘突出症患者的临床资料,所有患者行PETD并钙化物取出,其中L_5/S_1节段4例,L_4/L_5节段16例。所有患者术前均行腰椎CT和MRI检查,根据钙化物的形态和位置进行分型,对突出物与行走神经根的位置关系进行分型,根据不同的分型,采取不同的手术策略。采用疼痛视觉模拟量表(VAS)评分和Mac Nab标准对疗效进行评价。结果所有手术顺利完成,患者随访3个月。术后复查腰椎CT示症状侧旁中央及神经根管部位的钙化物被完全切除,中央部及无症状侧仍残留部分钙化物。所有患者术后腰腿痛的VAS评分为0~1分,术后Mac Nab标准评价为优。结论 PETD避免过度牵拉神经根,可降低术中发生神经损伤的概率,可切除神经根管处的钙化物有效缓解患者症状,治疗钙化型腰椎椎间盘突出症安全、有效。     

经椎间孔入路经皮内窥镜下椎间盘切除术治疗脱出型和游离型腰椎椎间盘突出症

目的评价经椎间孔入路经皮内窥镜下椎间盘切除术(PETD)治疗脱出型和游离型腰椎椎间盘突出症(LDH)的临床效果。方法 2012年7月—2014年9月,对被诊断为脱出型和游离型LDH的48例患者采用PETD治疗。所有患者根据髓核脱出(NPP)的方向和远近分4型:Ⅰ型3例,Ⅱ型11例,Ⅲ型26例,Ⅳ型8例。采用疼痛视觉模拟量表(VAS)评分和改良Mac Nab标准评价临床疗效。结果所有病例手术均顺利完成,手术时间35~90 min,平均65 min;出血量5~20 mL,平均10 mL;住院时间2~30 d,平均3.5 d。2例患者术后出现患侧肢体麻木加重,1例术后出现脑脊液漏,1例术后出现椎间隙感染,经对症治疗后症状均消失。术后总体满意度为87.5%;各型分别为Ⅰ型67.7%,Ⅱ型90.9%,Ⅲ型92.3%,Ⅳ型75.0%。所有患者术后疼痛症状均有所缓解,末次随访VAS评分与术前相比,差异均有统计学意义(P0.05)。所有患者术后15~45 d(平均30 d)均恢复正常工作。结论 PETD治疗脱出型和游离型LDH安全且有效,短期疗效满意。     

骶骨倾斜移位与L5S1椎间盘退变之间的相关性生物力学分析

目的 :应用生物力学的方法分析骶骨倾斜移位与L_5S_1椎间盘退变之间的相关性。方法:2011年7月至2013年7月,选取81例腰椎间盘突出症(LDH)合并骶髂关节紊乱的患者,其中男45例,女36例;年龄18~65岁,平均(45.39±1.30)岁;病程1~60个月,平均(12.64±2.19)个月。拍摄患者腰椎侧位X线片81张,测量腰椎曲度,L4-L5或L5-S1椎间隙的距离及腰骶角,然后进行相关性分析。结果:在L_5S_1DH中女性患者的腰椎曲度明显大于男性患者[(22.18±8.62)°vs(16.17±4.97)°,P0.05]。LDH中腰椎曲度与腰骶角呈正相关性(R=0.48,P0.01,y=7.25+0.38x,P0.01);男性患者在L4,5DH中较明显(R=0.55,P0.05,y=5.80+0.43x,P0.01);女性患者在L_5S_1DH中尤为明显(R=0.74,P0.01,y=0.91x-5.30,P0.01)。L4,5DH中腰骶角与L4,5椎间隙之间呈正相关性(R=0.27,P0.05);而在L_5S_1DH中L_5S_1椎间隙与腰骶角无相关性(P0.05)。结论:骶骨倾斜移位与L_5S_1椎间盘退变之间密切相关,为临床治疗慢性顽固性L_5S_1椎间盘突出症提供了一新的认识理念与治疗途径。     

针灸联合散瘀止痛散治疗腰椎间盘突出症的临床疗效

目的探讨针灸联合散瘀止痛散治疗腰椎间盘突出症的临床疗效。方法选取南华大学附属长沙中心医院2018—2019年收治的腰椎间盘突出症患者87例,按照数字奇偶法分为对照组42例和观察组45例。2组均予以常规牵引、推拿、防寒保暖,对照组加用针灸治疗,观察组加用针灸联合散瘀止痛散治疗。比较2组腰腿疼痛程度、腰椎功能,治疗前后血清炎性因子水平,包括肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)及基质金属蛋白酶3(MMP-3)。结果治疗前2组视觉模拟评分法(VAS)评分、日本骨科学会(JOA)评分比较,差异无统计学意义(P>0.05);治疗后观察组VAS评分低于对照组,JOA评分高于对照组(P<0.05)。治疗前2组血清TNF-α、IL-1β、MMP-3水平比较,差异无统计学意义(P>0.05);治疗后观察组血清TNF-α、IL-1β、MMP-3水平低于对照组(P<0.05)。结论针灸联合散瘀止痛散治疗腰椎间盘突出症的临床疗效确切,可减轻患者腰腿疼痛程度,促使腰椎功能恢复,明显缓解机体炎性反应。     

丹参酮ⅡA磺酸钠注射液联合胺碘酮治疗室性早搏的疗效观察

目的探讨丹参酮Ⅱ_A磺酸钠注射液联合胺碘酮治疗室性早搏的疗效。方法选取2018年7月-2020年3月阜阳市肿瘤医院收治的96例室性早搏患者作为研究对象,按照治疗方法将患者分为对照组和观察组,每组各48例。对照组患者口服盐酸胺碘酮片,0.2 g/次,3次/d。观察组在对照组的基础上静脉滴注丹参酮Ⅱ_A磺酸钠注射液,80 mg/次,1次/d。两组均连续治疗2周。观察两组患者的临床疗效,同时比较两组治疗前后的室性早搏次数、ST段下移时间、ST段压低距离、每搏输出量（SV）、心输出量（CO）、阻力指数（RI）。结果治疗后,观察组临床总有效率93.75%,显著高于对照组的79.17%,差异有统计学意义（P<0.05）。治疗后,两组的室性早搏次数、ST段下移时间、ST段压低距离均显著降低（P<0.05）;观察组治疗后的室性早搏次数、ST段下移时间、ST段压低距离均低于对照组,差异有统计学意义（P<0.05）。治疗后,两组的SV、CO显著升高,RI显著降低（P<0.05）;观察组治疗后的SV、CO高于对照组,RI低于对照组,差异有统计学意义（P<0.05）。结论丹参酮Ⅱ_A磺酸钠注射液联合胺碘酮可提高室性早搏的疗效,改善患者血流动力学,改善心电图的水平,安全性较好,具有良好的临床研究价值。     

电磁导航辅助经椎间孔入路经皮内窥镜下腰椎椎间盘切除术治疗腰椎椎间盘突出症

目的 探讨电磁导航技术应用于经椎间孔入路经皮内窥镜下腰椎椎间盘切除术（PETD）治疗腰椎椎间盘突出症（LDH）的安全性、准确性和可行性。方法 回顾性分析2019年4月—2021年4月采用电磁导航辅助PETD治疗的L₄/L₅节段LDH患者37例,记录住院时间、住院费用及并发症发生情况,记录手术时间以分析该技术学习曲线。分别于术前、术后1 d和末次随访时采用疼痛视觉模拟量表（VAS）评分、Oswestry功能障碍指数（ODI）评估腰腿痛程度和腰椎功能;采用健康调查简表（SF-36）评分评估患者生活质量;术后采用改良MacNab标准评定手术疗效满意度,并分析满意度为优与各项评估指标之间的相关性。结果 所有手术顺利完成,无术中转为开放手术病例,患者随访时间> 12个月。所有患者术后VAS评分、ODI较术前明显改善,且末次随访时较术后1 d进一步改善,差异均有统计学意义（P < 0.05）。术后SF-36评分8个维度评分较术前明显改善,差异均有统计学意义（P < 0.05）。改良MacNab标准评定疗效满意度,优27例,良6例,可4例,优良率为89.2%;满意度为优与各项评估指标之间未发现相关性。结论 电磁导航辅助PETD治疗LDH安全、有效、准确、微创,提高了穿刺和减压的安全性,减少了辐射暴露及并发症的发生,其临床疗效不受患者人口学特征和术前腰腿痛程度的影响。     

基于p38MAPK信号通路分析咪达唑仑对腰椎间盘突出症模型大鼠疼痛的影响CSCD

目的:探究基于p38MAPK信号通路分析咪达唑仑对腰椎间盘突出症模型大鼠疼痛的影响。方法:选取50只SPF级别SD健康大鼠,雌雄各半,随机分为正常组,模型组,低、中、高剂量组,模型组和低、中、高剂量组先建立腰椎间盘突出症模型。正常组、模型组大鼠腹腔注射生理盐水,低、中、高剂量组大鼠腹腔注射咪达唑仑,分别按30、60、90 mg/kg给药。采用酶联免疫吸检测大鼠血清中白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、5-羟色胺(5-hydroxytryptamine,5-HT)、β-内啡肽(β-endorphin,β-EP)、P物质(substance P,SP)、神经肽Y(neuropeptide Y,NPY)水平,采用Western blot检测各组大鼠组织中p38 MAPK,基质金属蛋白酶3(matrix metalloproteinase-3,MMP3)蛋白表达。结果:模型组大鼠TNF-α、IL-1β、β-EP水平较正常组高,5-HT水平低于正常组(P<0.05);低、中、高剂量组大鼠TNF-α、IL-1β、β-EP水平较模型组下降、5-HT水平升高(P<0.05)。模型组大鼠较正常组SP、NPY水平上升(P<0.05);低、中、高剂量组较模型组大鼠SP、NPY水平下降(P<0.05)。模型组较正常组大鼠p38 MAPK、MMP-3表达上升(P<0.05),低、中、高剂量较模型组大鼠p38 MAPK、MMP-3表达下降(P<0.05)。结论:咪达唑仑可以改善腰椎间盘突出症模型大鼠的免疫炎症反应,可能是通过p38MAPK信号通路调控来实现的。     

Highly specific SNP detection using 2D graphene electronics and DNA strand displacement

Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.DNA sequencing has opened new windows of opportunities for diagnosis of genetic disease (1), biological informatics (2), forensics (3), and environmental monitoring (4). Discrimination of a single mismatch in a long DNA strand is of significant importance and is essential to detect single nucleotide polymorphism (SNP). SNP is a single-nucleotide mutation in a gene sequence and varies among paired chromosomes, between individuals, and across biological species. SNP mutations can have dramatic influence on the health. They are markers for variety of diseases, including various forms of cancer, genetic disorders (5–7), and are of critical importance for successful practical implementation of the concept of personalized medicine (8). Thus, the development of biosensors detecting SNP mutations with high sensitivity and specificity is essential for effective personalized medicine approaches.Current DNA sequencing, including SNP detection, is achieved primarily by enzyme-based methods, using DNA ligase (9), DNA polymerase (9), and nucleases (10). These methods generate highly accurate genotyping. However, the methods are expensive and time-consuming. One of the common enzyme-free methods to detect SNPs uses hybridization of the target DNA to a probe on a microarray and detects their binding events with fluorescence microscopy/spectroscopy. Hybridization-based methods for SNP detection have several disadvantages, including cross-hybridization between allele-specific probes (11). This limits the detection of a single mismatch in long probe–target hybridization as the longer probes have more frequent cross hybridization. For example, a single mismatch in the center of a 15-bp probe–target duplex can be detected because there is a critical difference in the hybridization affinity between a perfect-matched and a single-mismatched hybridization. However, when the probe length is 40 or 50 nt, a single mismatch produces a relatively small difference between a perfect-matched and a single-mismatched hybridization. Thus, SNP detection is difficult with the simple hybridization-based methods. The typical length of probes used in microarrays is over 20 nt; cross-hybridization significantly reduces its reliability and specificity. To reduce cross-hybridization, redundancies in the array design are used to confirm detections of the same SNP or probe sequences are modified to control hybridization affinity (12–14). If cross hybridization were reduced or eliminated, fewer probes would be needed to obtain the same level of reliable analysis with longer probes (60–80 nt) (15), and longer probes provide more sensitive detection (16, 17).DNA strand displacement can be used to improve specificity even for a longer probe design. Strand displacement occurs when a DNA double helix exchanges one strand for another complementary strand (18). The newly introduced strand with higher affinity to one strand in the initial double helix displaces the other strand with lower affinity. Additionally, inosine or RNA can be used to control kinetics or Gibbs free energy of hybridization (19–22). Strand displacement has been a core technique in DNA nanomanipulation for over 20 years and has been used in several mechanical nanomachines (23), logic gates (24), and sensors (19, 25). Currently, strand displacement-based assays can discriminate SNPs efficiently, by controlling competition between the initially hybridized parts in the double-stranded or hairpin-structured probe and probe-to-target hybridization (12).The broadly used SNP detection methods, even with the most advanced probe design, typically use the fluorescence-based readout (26). However, fluorescence-based sensors have life-time and background limitations. Moreover, they require fluorimeters or laser scanners to for the quantitative analysis of the optical signal and hence the application of optical probes depends on a sophisticated and expensive laboratory-setting. Electrical detection of DNA sequences using the field effect transistor (FET) presumably lowers the limit of detection to the femto-molar level (27). FETs are of particular interest because they can be used as highly sensitive bio-molecular sensors and could be efficiently integrated using electric chip designs, including silicon-based FET (28), 1D carbon nanotubes (29), and Si nanowires (30). Nanotubes and nanowires allow better sensitivity due to their high surface-area-to-volume ratio and the sensitive carrier mobility to the electric field (charge density). However, the complicated top-down fabrication processes and random array of the nanowires and nanotube are costly and unreliable. Graphene, a 2D material, is attractive because it is a single atom thick sheet that is easy to fabricate uniformly over a large area. Ambipolar field effect, high carrier mobility, low intrinsic electrical noise, mechanical strength, and flexibility collectively represent some of the advantages that make graphene a promising material for FET bio-sensing (31). First-generation graphene-based biosensors have been developed to successfully detect bacteria (32), glucose (33), protein (34), pH (35), and DNA (34, 36).FET-based DNA biosensors currently use a single-stranded probe to detect hybridization. When the probe binds to the target strand, a double helix forms and the binding results in a measureable change in the electric charge over the active layer of the FET (27, 37). In currently available FET-DNA biosensors, the average length of the probe and the target is 10 to ∼25 nt (27, 29, 37, 38). In the case of a 25-nt probe, the signal difference between a fully complementary target and a single-mismatched one is less than 50%, and the target is significantly smaller than one reported with other biosensors using short probes (29).Given the inherent disadvantages of the current probe’s design used in graphene FET biosensors, we reasoned that design and fabrication of biosensors using a strand displacement-based probe architecture on a graphene FET would provide improved specificity and resolution. In this paper, DNA strand displacement-based probe is successfully designed and used on a graphene FET biosensor for label-free detection of a single mismatch with higher specificity than that of a single-stranded probe DNA.Architecture of double-stranded (DS) probes was conceived to facilitate the design compatibility of a graphene FET biosensor for the electrical sensing of DNA strand displacement. A DS probe containing targeted inosine substitutions and optimized toehold lengths was first tested with fluorescence/quencher technology to demonstrate an efficient single-mismatch discrimination. Then, the nonfluorescently labeled DS probe was attached on a graphene FET to reproduce the SNP discrimination based on the electrical sensing of DNA strand displacement. A liquid gate was used to obtain current–voltage (I-V) curve with DNA in buffer solution. I-V curve shifts and changes in resistance were monitored with fully complementary (perfect-match) and single-mismatched DNA sequences. With this combination of the electrical sensor and dynamic DNA nanotechnology, a single mismatch was detected in 47 nt of DNA with high resolution. To our knowledge, this is the first report of the successful electrical detection of strand displacement in long DNA strands by sensing the charge difference before and after strand displacement without any labeling or additional processes.     

Initial varus displacement of proximal humerus fractures results in similar function but higher complication rates

PurposeTo investigate the effect of initial varus or valgus surgical neck alignment on outcomes of patients who sustained proximal humerus fractures treated with open reduction and internal fixation (ORIF).MethodsAn institutional review board approved database of proximal humerus fractures treated with locked plates was reviewed. Of 185 fractures in the database, 101 fractures were identified and met inclusion criteria. Initial varus displacement was seen in 47 fractures (OTA types 11.A2.2, A3.1, A3.3, B1.2, B2.2, C1.2, C2.2, or C2.3) and initial valgus displacement was observed in 54 fractures (OTA types 11.A2.3, B1.1, C1.1, or C2.1). All patients were treated in a similar manner and examined by the treating physician at standard intervals. Functional outcomes were quantified via the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and physical examination data at 12 months. Radiographs were reviewed for complications of healing. Additionally, complication rate and reoperation rate were investigated.ResultsPatients who presented with initial varus displacement had an average age of 59.3 years, while patients in the valgus group had an average age of 62.4 years. Overall, there was no statistically significant difference in age, sex distribution, BMI, fracture parts, screws used, or implant plate type between the two groups. At a minimum 12 months follow up, there was no significant difference in DASH scores between those presenting with varus versus valgus fracture patterns. In addition, no significant differences were seen in final shoulder range of motion in any plane. Overall, 30 patients included in this study developed a complication. A significantly greater number of patients in the initial varus cohort developed complications (40.4%), as compared to 20.3% of patients in the initial valgus cohort (P = 0.03). Fourteen patients in this study underwent reoperation. Nine of these patients were in the varus cohort, while 5 were in the valgus cohort (P = 0.15).ConclusionsIn this study, initial surgical neck displacement in varus or valgus was found to not significantly affect functional outcome. Based upon our findings, patients with varus displaced proximal humerus fractures are at a greater risk of developing postoperative complications than those who present with initial valgus displaced fracture patterns.