线粒体复合体在肾脏疾病中的研究进展

肾脏是富含线粒体的器官之一,其正常运行依赖于线粒体氧化磷酸化(oxidative phosphorylation,OXPHOS)为细胞供能.线粒体复合体(mitochondrial complex,MC)构成了线粒体呼吸链(mitochondrial respiratory chain,MRC),具有电子传递和质子转移的功能,参与OXPHOS的过程.近年的研究表明,MC参与了肾脏疾病的发生发展,MC在不同的肾脏疾病中作用不尽相同.本文旨在系统综述MC的功能,总结其在急性肾损伤(acute kidney injury,AKI)、以糖尿病肾病(diabetic kidney disease,DKD)为主的慢性肾脏病(chronic kidney disease,CKD)、肾脏肿瘤、线粒体DNA(mtDNA)疾病等不同肾脏病领域中的作用,分析探讨MC作为新的靶点在肾脏疾病诊治中的潜在价值.     

Urinary stone analysis on 12,846 patients: a report from a single center in China

We reported a retrospective review of the urinary stone compositions in 12,846 patients. Data on urinary stone compositions analyzed between January 2003 and December 2012 in our center were collected. Infrared spectroscopy was used for stone analysis. Predominant stone component was recorded. Patients were divided into four age groups: 0–18, 19–40, 41–60, and 61–92, and five categories by components. In order to determine the change of stone characteristics with respect to time, data were also divided into two periods, 2003–2007 and 2008–2012. A total of 12,846 stones were included in this study. The age of the patients ranged from 1 to 92 years with 7,736 males and 5,110 females. Stone made of single component was rare, 2.61 %. Calcium oxalate stone was the most common component at 82.56 %. Calcium oxalate and uric acid stones were more common in male than in female. The incidence of calcium phosphate stones and uric acid stones had increased during the past 5 years, while calcium oxalate stones decreased. We found the highest incidence of stone disease in the 41–60 years old group and the lowest in the 1–18 years old for both genders. Calcium oxalate was the dominant component in every group but was more prevalent in 19–40 years group. The percentage of magnesium ammonium phosphate stone and uric acid stone increased with age.     

The relationship between spinopelvic parameters and clinical symptoms of severe isthmic spondylolisthesis: a prospective study of 64 patients

Purpose

To investigate the relationship between spinopelvic parameters and clinical symptoms for patients with severe isthmic spondylolisthesis.

Methods

A series of spinopelvic parameters were measured in 64 patients with L5 severe isthmic spondylolisthesis. The patients were divided into two groups according to Oswestry score obtained preoperatively, i.e. mild or severe low back pain group. T test was used to compare parameters between two groups, and multiple linear regression analysis was employed to investigate the association between parameters and Oswestry score.

Results

Compared with two group patients, parameters of spondylolisthesis grade, pelvic tilt (PT), lumbar lordosis (LL), T9 tilting angle (T9TA), sacro-femoral horizontal distance (SFHD), distance between perpendicular line through C7 and sacrum (SC7D), pelvic tilt/sacral slope (PT/SS), sacro-femoral horizontal distance/vertical distance (SFHD/SFVD), and lumbar lordosis/thoracic kyphosis (LL/TK) were significantly increased in severe low back pain group, while SS and SFVD were significantly decreased, and no significant difference was found for pelvic incidence (PI) and TK. The statistical analysis showed that spondylolisthesis grade, PT, SC7D, LL, SFHD, PT/SS, SFHD/SFVD, and LL/TK had a significant positive correlation with Oswestry score, with an order of spondylolisthesis grade > PT/SS > SC7D > PT > SFHD/SFVD > SFHD > LL/TK > LL. No significant correlation was found for PI, TK, T9TA with Oswestry score, while SS and SFVD had a significant negative correlation with Oswestry score, with an order of SS > SFVD.

Conclusions

The spinopelvic parameters (spondylolisthesis grade, SS, PT, SC7D, LL, SFVD, SFHD, PT/SS, SFHD/SFVD, LL/TK) are significantly correlated with clinical symptoms of severe isthmic spondylolisthesis in patients. The association of the exacerbation of low back pain with SS (correlation coefficient −0.981, strong) and SFVD (correlation coefficient −0.802, strong) is the most significant correlation.     

药物临床试验各环节的质量管理

目的 制定药物临床试验各环节的质量管理要点,探求科学、有效的质量管理办法,保证药物临床试验过程的规范、可控,提高药物临床试验的质量水平。方法 通过文献查找并结合临床实践,以方案设计、项目审批、团队组成、过程管理、资料管理等方面为切入点,分析药物临床试验实施前、中、后期的质量管理要点,探讨解决问题,提高项目质量的管理方法及措施,建立质量保证机制。结果 做好药物临床试验的质量管理,应重点做好方案审核、人员管理、过程管理、用药管理、不良事件管理等工作,充分发挥研究者、机构办公室与伦理委员会等多方的作用,立项前严格审核,过程中时刻监控,结束后层层把关,从细节抓起,共同监督。结论 药物临床试验检验着药品有效性和安全性两大基本属性,是新药上市的最后防线。只有做好质量管理工作,采取有效机制尽量避免试验各环节的失误,才能有效保证临床试验过程的规范性和真实性,切实保障受试者的权益。     

首发症状为急慢性胰腺炎的胰腺癌诊断与治疗

目的 总结首发症状为急慢性胰腺炎的胰腺癌的诊断与治疗经验.方法 回顾性分析2003年1月至2014年6月大连医科大学附属第一医院和大连医科大学附属中心医院收治的13例以急慢性胰腺炎为首发症状的胰腺癌患者的临床资料.患者术前行实验室和影像学检查,术前根据肿瘤部位、进展程度和患者意愿决定治疗方案.治疗方法包括手术、放疗、化疗或其他对症支持治疗.手术患者术中及术后行病理学检查.通过电话随访患者出院后生存情况,随访时间截至2014年7月.结果 13例患者表现为腹痛,7例表现为腰背痛.7例患者体质量下降.13例患者均无胰腺癌家族史.13例患者中1例拒绝采血化验,12例患者血清CA19-9值升高(其中11例＞1×105 U/L),5例患者血清CEA升高.13例患者均行腹部CT平扫或增强扫描,3例患者行MRI检查,3例患者行超声检查.肿瘤位于胰头部9例、胰颈部2例、胰尾部2例.肿瘤大小为1.7 cm×1.7 cm～4.9 cm ×4.8 cm.7例患者见胆总管、肝内胆管、胰管扩张.3例患者肿瘤侵犯肠系膜上静脉.腹腔内淋巴结明显肿大者4例,腹腔积液者3例.CT检查证实胆囊结石2例,MRCP检查证实胆总管结石1例.超声检查均提示胰腺体积增大,其中2例提示主胰管扩张.10例患者经影像学检查排除腹腔其他部位恶性肿瘤证实为胰腺癌晚期.依据影像学进行分期,临床分期为Ⅱ期5例、Ⅳ期8例.2例患者行胰十二指肠切除术,其中1例术后行放化疗.1例患者行姑息性胆肠吻合+胃空肠吻合术.10例非手术患者中1例施行放疗,2例施行化疗,其余7例患者采取对症支持治疗.2例行胰十二指肠切除患者的病理学检查结果均为中、低分化腺癌,瘤体大小分别为4.0 cm ×3.0 cm×2.5 cm和2.5 cm×2.0cm×1.0cm.13例患者中3例失访.慢性胰腺炎为首发症状的患者生存时间为0.5 ～10.0个月,中位生存时间为3.0个月.急性胰腺炎为首发症状的患者生存时间为2.0 ～6.0个月,中位生存时间为4.5个月.4例CEA升高的患者,出院后平均生存时间为3.5个月,5例CEA未升高的患者出院后平均生存时间为5.4个月.10例随访患者在随访期内均因胰腺肿瘤转移或复发死亡.结论 首发症状为急慢性胰腺炎的胰腺癌临床症状不典型,早期诊断较为困难,确诊时多为晚期,预后较差.联合实验室和影像学检查,并依据病情变化动态追踪可提高诊断的准确性.治疗采用以外科手术为主的综合治疗.     

Inclusion of a universal tetanus toxoid CD4 T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines

Currently available live oral rotavirus vaccines, Rotarix^® and RotaTeq^®, are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4⁺ T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20 μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50 μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4⁺ T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or preferably in bivalent formulation to provide antigenic coverage of most of the G types of global importance.     

Decoding the individual finger movements from single‐trial functional magnetic resonance imaging recordings of human brain activity

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non‐invasively recorded human brain activation is crucial for implementing a brain–machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single‐trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor‐related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial–temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non‐invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI‐based brain–machine interface for finger movement.     

闭合性十二指肠损伤的临床疗效观察

目的 探讨闭合性十二指肠损伤的有效治疗方法。方法 对1999～2006年我院收治的20例闭合性十二指肠损伤患者的临床资料进行回顾性分析。结果 20例患者中治愈19例,治愈率95％,死亡1例。结论 闭合性十二指肠损伤易被漏诊,早期诊断并选择合理的术式,术后充分引流是提高治愈率、降低并发症和死亡率的关键。     

调整肌松复合手法治疗非椎动脉型颈性眩晕60例临床研究

目的观察调整肌松复合手法治疗非椎动脉型颈性眩晕的临床疗效。方法120例患者随机分为2组。治疗组60例采用调整肌松复合手法治疗,对照组60例予西比灵口服、颈椎牵引治疗。2组均10日为1个疗程,2个疗程后统计疗效。结果治疗组治愈率为65.0%,对照组治愈率26.7%,2组比较有显著性差异(P<0.01);2组治疗后眩晕评分、X线表现的变化率均有统计学意义(P<0.01)。结论调整肌松复合手法治疗非椎动脉型颈性眩晕效果显著。