DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

The association between physical activity time and neuropathy in longstanding type 1 diabetes: A cross-sectional analysis of the Canadian study of longevity in type 1 diabetes

AimPhysical activity (PA) is recommended to improve glycemic control in T1D; however, the effect of PA on distal symmetric polyneuropathy (DSPN) and cardiac autonomic function in longstanding T1D is unknown.MethodsData from 75 participants were collected as part of the Canadian Study of Longevity in T1D. Participants completed a physical exam, medical history, extensive complications phenotyping and reported their daily PA from the preceding 12-months. Pearson and Spearman correlations were used to assess PA time and complications variables. Linear regression was used to test associations between PA time, neurological and electrophysiological measures. Univariable regression was used to indicate the change in the given independent variables associated with a 30-min increase in PA per week.ResultsParticipants were 66 ± 8 years old with diabetes duration of 54 [52,58] years, HbA_1c was 7.3 ± 0.8, 65(89%) had DSPN. Weekly PA time was 156 ± 132 min, and 35(47%) reported ≧150 min/week. Participants with DSPN reported lower PA time compared to individuals without DSPN (141 ± 124 min/week vs. 258 ± 129 min/week; p = 0.015). PA time was associated with better cooling detection threshold (r = 0.24; p = 0.043), peroneal and sural amplitude (r = 0.36; p = 0.0017, r_s = 0.26; p = 0.024) and conduction velocity (r_s = 0.28; p = 0.015, r = 0.23; p = 0.050). Linear regression adjusting for age and HbA1c, showed that for each 30-min of PA there was a 0.09mv higher peroneal amplitude (p = 0.032) and 0.048 ms lower peroneal F-wave latency (p = 0.022).ConclusionIn longstanding T1D, PA time is associated with superior large nerve fibre function in the lower limbs and some better measures of small nerve fibre function.     

多功能套针浮刺疗法治疗神经根型颈椎病——一项随机对照观察研究＊

目的 评价多功能套针浮刺疗法对神经根型颈椎病的临床疗效。方法 选取256例神经根型颈椎病患者，按随机数字表法分为观察组与对照组各128例。观察组应用多功能套针浮刺疗法进行干预，对照组为常规针刺治疗。两组患者均治疗7天。分别于治疗前后观察两组患者的简化McGill疼痛问卷（SF-MPQ）、国际标准颈椎功能障碍指数（NDI）和田中靖久颈椎病症状20分法量表评分，并于治疗结束后3个月观察复发率。结果 两组患者治疗后的SF-MPQ量表评分、NDI量表评分及田中靖久颈椎病症状20分法评分与治疗前相比均有改善（P<0.05），且观察组优于对照组（P<0.05）；两组患者于治疗后3个月随访，SF-MPQ量表评分与治疗后相比均有改善，且观察组优于对照组（P<0.05）；观察组临床疗效总有效率为96.88%，愈显率为81.25%；对照组总有效率为78.13%，愈显率为46.88%，观察组优于对照组（P<0.05）。结论 应用多功能套针浮刺疗法治疗神经根型颈椎病临床疗效显著，见效较快，可有效降低其复发率，且作用稳定，效果持久，值得临床推广应用。     

Fatigue analysis of restored teeth longitudinally cracked under cyclic loading

ObjectiveTo investigate the fatigue behavior of restored teeth, in particular the mechanisms of longitudinal dentinal cracking under cyclic mechanical loading, using finite element analysis (FEA) and the stress-life (S-N) approach.MethodsTen root-filled premolars restored with resin composites were subjected to step-stress cyclic loading to produce longitudinal cracks. Fracture loads and number of cycles completed at each load level were recorded. FEA was used to predict the stress amplitude of each component under the global cyclic load. Both intact and debonded conditions were considered for the dentin-composite interface in the FEA. The predicted stress concentrations were compared with the fracture patterns to help elucidate the failure mechanisms. The S-N approach was further used to predict the lifetimes of the different components in the restored teeth. Cumulative fatigue damage was represented by the sum of the fractions of life spent under the different stress amplitudes.ResultsLongitudinal cracks were seen in ~50% of the samples with a mean fracture load of 770 ± 45 N and a mean number of cycles to failure of 32,297 ± 12,624. The longitudinal dentinal cracks seemed to start near the line angle of the cavity, and propagated longitudinally towards the root. The sum of fractions of life spent for the dentin-composite interface exceeded 1 after ~7000 cycles when that for dentin was much lower than 1, indicating that interfacial debonding would occur prior to dentin fracture. This was supported by micro-CT images showing widened interfacial space in the cracked samples. In the debonded tooth, FEA showed dentinal stress concentrations at the gingival wall of the cavity, which coincided with the longitudinal cracks found in the cyclic loading test. The sum of fractions of life spent for dentin was close to 1 at ~30,000 cycles, similar to the experimental value.SignificanceDebonding of the dentin-composite interface may occur prior to longitudinal cracking of dentin in root-filled teeth under cyclic loading. The approximate time of occurrence for these events could be estimated using fatigue analysis with stresses provided by FEA. This methodology can therefore be used to evaluate the longevity of restoration designs for root-filled teeth.     

Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.     

Automatic Grading Assessments for Knee MRI Cartilage Defects via Self-ensembling Semi-supervised Learning with Dual-Consistency

Knee cartilage defects caused by osteoarthritis are major musculoskeletal disorders, leading to joint necrosis or even disability if not intervened at early stage. Deep learning has demonstrated its effectiveness in computer-aided diagnosis, but it is time-consuming to prepare a large set of well-annotated data by experienced radiologists for model training. In this paper, we propose a semi-supervised framework to effectively use unlabeled data for better evaluation of knee cartilage defect grading. Our framework is developed based on the widely-used mean-teacher classification model, by designing a novel dual-consistency strategy to boost the consistency between the teacher and student models. The main contributions are three-fold: (1) We define an attention loss function to make the network focus on the cartilage regions, which can both achieve accurate attention masks and boost classification performance simultaneously; (2) Besides enforcing the consistency of classification results, we further design a novel attention consistency mechanism to ensure the focusing of the student and teacher networks on the same defect regions; (3) We introduce an aggregation approach to ensemble the slice-level classification outcomes for deriving the final subject-level diagnosis. Experimental results show that our proposed method can significantly improve both classification and localization performances of knee cartilage defects. Our code is available on https://github.com/King-HAW/DC-MT.     

多元化联合教学模式在超声引导下疼痛介入治疗中的应用

目的探讨多元化联合教学模式在超声引导下疼痛介入治疗教学中的应用效果。方法选择2018年1月至2020年12月在北京大学第三医院疼痛科进修的30名医师作为研究对象,将其分为对照组与观察组;对照组采用常规教学模式;观察组采用多元化联合教学模式,比较两组医师技能考核成绩、教学质量评分和满意度评分。结果观察组医师技能考核成绩优良率为93.3%,高于对照组的73.3%(P<0.05);观察组医师对基础理论知识掌握、临床思维能力的提高、学习兴趣的激发、疾病诊治能力的提高4个方面的评分均高于对照组(P<0.01)。结论多元化联合教学模式可促进超声引导下疼痛介入治疗技能的提高,有利于提高学员的综合临床能力。