超早期小骨窗开颅血肿清除术治疗老年高血压脑出血的临床效果

目的探讨超早期小骨窗开颅血肿清除术治疗老年高血压脑出血(HICH)的临床效果。方法回顾性分析2018年1月至2019年3月在我院接受小骨窗开颅血肿清除术治疗的86例老年HICH患者的病例资料,按照患者出血至手术间隔时间分为观察组(≤出血后6 h)与对照组(出血后7~24 h),每组43例。比较两组的治疗效果。结果观察组达到血肿完全清除患者占比高于对照组(P<0.05)。两组术后再出血率比较,差异无统计学意义(P>0.05)。术后,两组患者的NSE、NPY、D-D水平均显著降低,且观察组低于对照组(P<0.05)。手术后6个月,观察组GOS评分高于对照组,且NIHSS评分低于对照组(P<0.05)。手术后6个月,两组SIS及Barthel指数评分均显著高于术前,且观察组高于对照组(P<0.05)。结论超早期小骨窗开颅血肿清除术治疗老年HICH有良好的效果,不仅可提高血肿清除率,保护脑神经,改善患者的神经功能和生活质量,而且不增加再出血风险。     

138例乳腺癌的超声诊断

目的：探讨二维与彩色血流频谱多普勒超声对乳腺癌诊断的实用价值。方法：对经手术病理证实的138例乳腺癌的超声图像进行分析，包括其形态、边界、内部回声、纵横比、钙化灶、后方衰减及侧方声影观察肿块内及周边血流情况。结果：典型乳腺癌肿块的特征为形态不规则，内部回声不均，“恶性晕”征，纵横比例〉1，砂粒样钙化，后方衰减，同时彩色多普勒检出较丰富的血流。结论：二维与彩色血流频谱多普勒超声诊断乳腺癌有较高的诊断价值。     

O1和O139群霍乱弧菌超级整合子VchintIA基因的变异

目的 研究不同血清群(型)霍乱弧菌超级整合子整合酶基因(VchintIA)的变异及其与霍乱弧菌分类的关系。 方法 使用聚合酶链反应(PCR)和序列测定的方法对VchintIA基因进行扩增和序列分析。 结果 在实验菌株中,O1El Tor和O139群霍乱弧菌产毒株以及毒素共调菌毛(toxin co-regulated pilus, tcp)基因簇阳性的O1群非产毒株的VchintIA序列完全一致,tcp基因簇阴性的O1群非产毒株的VchintIA序列在核苷酸水平上与产毒株不同,但是在氨基酸水平上相同。O139非产毒株的VchintIA序列在核苷酸和氨基酸水平上均与产毒株的VchintIA不同。 结论 O1和O139霍乱弧菌超级整合子VchintIA存在核苷酸和氨基酸水平上的变异,O139非产毒株中VchintIA的变异与其整合子内部的结构可能相关。     

超大型医院医疗不良事件之管理

医院有效事前监测、管控医疗不良事件,是保障患者安全、提高医疗质量的管理措施之一。超大型医院对医疗不良事件管理的实战中,建立、实施医疗安全隐患事件关键监测指标、医疗安全隐患事件筛查程序指标,积极开展医疗不良事件后台监管工作,切断医疗安全隐患事件向医疗风险事件演变、医疗风险事件向医疗纠纷事件演变的环节,保障患者安全。     

349例重型病毒性肝炎的临床特点及病毒标志物检测结果分析

目的了解重型病毒性肝炎住院病例的临床及病原学特点,探讨慢性肝炎重症化及其预后的关系。方法采用回顾性调查方法,对349例重型病毒性肝炎的临床特点及病毒标志物检测结果进行分析。结果349例重型病毒性肝炎患者中,发生于急性肝炎的28例,发生于慢性肝炎有明确肝病史和无明确肝病史的分别为245例和76例;引起重型肝炎的病毒中以HBV单一或重叠感染率最高,占82.2%(287/349),6例(1.72%)未能确定病原,未发现单一HAV、HDV和HGV感染者,HBV重叠HEV感染者病死率为65.2%(15/23),HEV重叠其他肝炎病毒感染者的病死率为60%(18/30),均比单一HBV或单一HEV感染者高(P<0.01和P<0.05)。结论重型肝炎仍以HBV感染为主,HBV和HEV重叠感染可以加重病情、病死率高。     

乙型肝炎患者血清HBV DNA负荷和肝组织超微结构损伤的相关性

探讨乙型肝炎患者血清HBV DNA负荷和肝组织超微结构损伤的相关性。采用免疫荧光定量聚合酶链和超微病理学技术,分别检测随机选择的40例乙型肝炎患者血清HBV DNA负荷和其肝组织超微结构损伤。血清 HBV DNA水平和肝组织某些超微结构损伤(线粒体肿胀、溶酶体增多、汇管区淋巴细胞浸润、Kupffer细胞增生、肝细胞淤胆和间质纤维组织增生)呈正相关,但不呈直线相关(re=0．21,t=1．12,P>0．05);血清HBV DNA水平和肝组织某些超微结构损伤(内质网增生扩张、高尔基体扩张、贮脂细胞增生、毛细胆管扩张淤胆、毛细血管增生)无相关性(P>0．05)。乙型肝炎患者血清HBV DNA负荷和其肝组织某些超做结构损伤有相关性。     

In vivo quantification of SPIO nanoparticles for cell labeling based on MR phase gradient images

Along with the development of modern imaging technologies, contrast agents play increasingly important roles in both clinical applications and scientific research. Super‐paramagnetic iron oxide (SPIO) nanoparticles, a negative contrast agent, have been extensively used in magnetic resonance imaging (MRI), such as in vivo labeling and tracking of cells. However, there still remain many challenges, such as in vivo quantification of SPIO nanoparticles. In this work, an MR phase gradient‐based method was proposed to quantify the SPIO nanoparticles. As a calibration, a phantom experiment using known concentrations (10, 25, 50, 100, 150 and 250 µg/ml) of SPIO was first conducted to verify the proposed quantification method. In a following in vivo experiment, C6 glioma cells labeled with SPIO nanoparticles were implanted into flanks of four mice, which were scanned 1–3 days post‐injection for in vivo quantification of SPIO concentration. The results showed that the concentration of SPIO nanoparticles could be determined in both phantom and in vivo experiments using the developed MR phase gradients approach. Copyright © 2014 John Wiley & Sons, Ltd.     

Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy

A new type of monoclonal antibody (mAb)‐based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a near‐infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, target‐selective necrotic cell death. However, tumor shrinkage takes several days to occur, making it difficult to detect earlier changes in the tumor. In this study, Panitumumab targeting the epidermal growth factor receptor (EGFR1) conjugated to IR700 was used to treat EGFR‐expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100 J cm^?2) in xenograft tumors in mice. Indocyanine green (ICG) dynamic imaging was evaluated for monitoring cytotoxic effects for the first hour after PIT. Our results demonstrated a statistical difference (p < 0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50 J cm^?2: 2.94 ± 0.35 vs 5.22 ± 0.92, p = 0.02; and 100 J cm^?2: 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) as early as 20 min post ICG injection. However, no significant difference (p > 0.05) in ICG intensity between control and PIT treated tumors was evident in the lower light exposure group at any time points up to 60 min (10 J cm^?2: 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; and 30 J cm^?2: 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07). Similarly, the retention index (background to corrected uptake ratio of ICG) varied with light exposure. In conclusion, ICG may serve as a potential indicator of acute cytotoxic effects of mAb‐IR700‐induced PIT even before morphological changes can be seen in targeted tumors. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.     

Hypertrophic cardiomyopathy β-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super relaxed state

Hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, associated with over 1,000 mutations, many in β-cardiac myosin (MYH7). Molecular studies of myosin with different HCM mutations have revealed a diversity of effects on ATPase and load-sensitive rate of detachment from actin. It has been difficult to predict how such diverse molecular effects combine to influence forces at the cellular level and further influence cellular phenotypes. This study focused on the P710R mutation that dramatically decreased in vitro motility velocity and actin-activated ATPase, in contrast to other MYH7 mutations. Optical trap measurements of single myosin molecules revealed that this mutation reduced the step size of the myosin motor and the load sensitivity of the actin detachment rate. Conversely, this mutation destabilized the super relaxed state in longer, two-headed myosin constructs, freeing more heads to generate force. Micropatterned human induced pluripotent derived stem cell (hiPSC)–cardiomyocytes CRISPR-edited with the P710R mutation produced significantly increased force (measured by traction force microscopy) compared with isogenic control cells. The P710R mutation also caused cardiomyocyte hypertrophy and cytoskeletal remodeling as measured by immunostaining and electron microscopy. Cellular hypertrophy was prevented in the P710R cells by inhibition of ERK or Akt. Finally, we used a computational model that integrated the measured molecular changes to predict the measured traction forces. These results confirm a key role for regulation of the super relaxed state in driving hypercontractility in HCM with the P710R mutation and demonstrate the value of a multiscale approach in revealing key mechanisms of disease.

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent genetic diseases of the heart, affecting over 1 in 200 individuals (1, 2), and is a leading cause of sudden cardiac death (3). HCM is characterized by cardiomyocyte hypertrophy, myofibril disarray, hypercontractility, and diastolic dysfunction, although there are substantial heterogeneity and complexity in the presentation of HCM in patients (4, 5). Tissue remodeling, including interstitial fibrosis, can eventually progress to heart failure and death (5–7). Over 1,000 causative mutations have been identified, with the majority in genes encoding sarcomeric proteins responsible for generating and regulating contraction. Roughly a third of mutations are located in β-cardiac myosin, the primary ventricular motor protein in humans (8). Increased ejection fraction has been observed in patients with pathogenic mutations in β-cardiac myosin without left ventricular (LV) hypertrophy, which suggests that hypercontractility may precede hypertrophic remodeling in some patients with HCM mutations in β-cardiac myosin (9).Because hypercontractility is often observed in HCM patients with mutations in β-cardiac myosin, HCM mutations were hypothesized to increase the activity of myosin at the protein level, resulting in increased force production at the sarcomere and cellular levels that propagates to the whole-organ level (10). Myosin protein activity is characterized by biochemical and biophysical measurements. The activity of actively cycling myosin interacting with actin is characterized by the rate of ATP turnover, the rate of detachment from actin, force production, step size, and actin-sliding velocity. Myosin that is not actively cycling resides in a super relaxed state (SRX) (11), associated with a folded-back conformation not available for actin interaction. Biochemical and biophysical assessments of HCM mutations in purified human β-cardiac myosin have revealed various changes in both actively cycling myosin (12–16) and SRX proportions (17–20).Myosin is a mechanoenzyme that harnesses the chemical energy from ATP hydrolysis to perform a force-producing power stroke. Its converter domain plays a critical role in facilitating this power stroke by coupling conformational changes originating from its nucleotide pocket to the rotation of its lever arm. This domain is a hot spot for pathogenic mutations (21–24). The P710 residue is located at the proximal edge of the converter domain, and at least three HCM mutations have been identified at this site, including P710R (25–27). The P710R mutation was identified in a cohort of patients with pediatric onset HCM (defined based on LV hypertrophy in patients 13 or younger), and echocardiograms of this cohort found significantly reduced LV end systolic dimension and increased fraction shortening suggesting hypercontractility (27). According to a recent meta-analysis, the average age of disease onset for HCM in patients without a known mutation is 44 y, and the average age of onset with mutations in β-cardiac myosin is 35 y (28). A previous report characterizing both early-onset and late-onset HCM mutations found that actively cycling heads with the P710R mutation have lower ATP turnover activity and duty ratio compared with both wild-type (WT) myosin and other HCM mutations (29). The discrepancy between this reduced function in actively cycling myosin and a potentially hypercontractile, early-onset clinical phenotype invites a comprehensive, multiscale assessment of the effects of the P710R mutation on myosin activity and SRX proportions.In the past, it has been difficult to determine early mechanisms of HCM disease triggered by mutations in β-MHC because of the inability to culture human cardiomyocytes. Samples from hearts obtained at the time of transplant or myectomy reflect a combination of primary and secondary pathologies. Rodents fail to recapitulate many human heart diseases, and their adult ventricles predominantly express the α-MHC isoform, which has different kinetics from β-MHC (30–32). However, the expansion of CRISPR/Cas-9 protocols for human induced pluripotent derived stem cell (hiPSC) gene editing coupled with efficient differentiation into cardiomyocytes (hiPSC-CMs) provides a valuable model system for studying early mechanisms of disease, especially mechanisms related to contractile alterations, in a controlled context (31). In the past, hiPSC-CM models have been limited by the relative immaturity of the cardiomyocytes and high population heterogeneity (33). In traditional two-dimensional culture, these cells have disorganized myofibrils, impaired calcium handling, and immature cell signaling (34, 35). However, recent advances in microengineered environments can provide external environmental cues that better recapitulate in vivo conditions to promote myofibril alignment and accelerate maturation of both contractile machinery and cell signaling (35, 36). While these engineering solutions can improve the functional maturity of hiPSC-CMs, they are still immature relative to adult cardiomyocytes in the heart (33). We have previously developed a hydrogel platform with rectangles of extracellular matrix (ECM) at a 7:1 aspect ratio (similar to that of cardiomyocytes in the left ventricle) that, combined with traction force microscopy (TFM), allows for single-cell assessment of both cellular organization and biomechanics (35–37). When combined with measurements of myosin function at the molecular level, these cellular measurements can provide validation of the molecular basis of force generation and resultant disease mechanisms of HCM.Finally, computational models can provide key insights into the interactions between related dynamic parameters and the resultant implications for the total production of force. Computational models incorporating different degrees of detail and different components of sarcomere structure have been used for decades to answer questions relating to fundamental muscle mechanics (38–47) and alterations to thin filament regulation in the context of cardiac disease and HCM (48, 49). A new model of myosin activity that incorporates an OFF state representative of the SRX state has recently been validated against experimental measurements of cardiac muscle (50). This study concluded that force-sensitive regulation of the OFF state significantly improves the fit to experimental data, but this model has not previously been used in the context of MHY7 mutations nor hiPSC-CMs (50).In this work, we used multiscale experimental techniques to assess the biomechanical effects of the HCM mutation P710R, which demonstrates decreased activity at the level of the motor domain yet increased force generation at the cell level. We furthermore used a computational model to integrate the molecular findings and found that altered regulation of the SRX state is an essential driver of hypercontractility for this mutation. Our multiscale experimental findings combined with computational modeling enabled us to assess the relative contributions of individual molecular parameters to cellular contraction.     

Response-guided peginterferon-alpha-2b plus ribavirin therapy for chronic hepatitis C patients with genotype 2 and high viral loads

Aims: Optimization of the duration of peginterferon‐α/ribavirin therapy in patients with hepatitis C virus (HCV) genotype 2 and high viral loads remains to be established. We sought to prospectively optimize the treatment duration based on their virological responses. Methods: Serum HCV RNA levels of less than 50 IU/mL at weeks 2 and 4, and of 50 IU/mL or more at week 4, were defined as a super‐rapid virological response (SRVR), rapid virological response (RVR) and late virological response (LVR), respectively. Treatment for 12, 24 or 48 weeks was assigned to the patients with an SRVR, RVR or LVR, respectively. However, patients with an LVR who expressed a desire to receive the standard therapy duration were given the 24‐week therapy. Results: The overall sustained virological response (SVR) rate was 78.1% (118/151). The SVR rate in the SRVR group was 93.8% (15/16), which was comparable to the 93.0% (66/71) SVR rate in the RVR group. In the LVR patients, the 48‐week treatment slightly increased the SVR rate to 76.5% (13/17) compared with the 51.1% (24/47) SVR rate in LVR patients who underwent the standard 24‐week treatment. The relapse rate in LVR patients was significantly decreased in patients treated for 48 weeks compared with patients treated for 24 weeks. Multivariate analysis identified the predictive factors for SVR as RVR, prior interferon therapy and total peginterferon‐α‐2b adherence in patients treated for 24 weeks. Conclusion: Response‐guided therapy may be effective and useful for optimization of the treatment duration.