Chronic inflammation and risk of lung cancer in older adults in the health,aging and body composition cohort study

Objectives

We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.

基于突触可塑性探讨电针改善大脑中动脉闭塞大鼠运动障碍的作用机制

目的：基于突触可塑性观察电针曲池、足三里对大脑中动脉闭塞（MCAO）大鼠运动障碍的改善。方法：将60只雄性SD大鼠随机分为假手术组、模型组、穴位组、非穴组，每组15只。采用Zea Longa线拴法制备MCAO大鼠模型，电针曲池、足三里，干预14 d。通过神经功能评分判断大鼠的神经功能缺损情况；CatWalk步态分析比较各组大鼠运动功能，TTC染色观察脑梗死体积，透射电镜观察突触超微结构和数量，免疫荧光检测缺血侧运动皮层突触相关因子突触后致密物-95（PSD-95)、突触蛋白的表达情况。结果：干预14 d后，与模型组比较，穴位组大鼠神经功能评分降低(P<0.05)；步行速度提高、双足支撑时间缩短(P<0.05)；脑梗死体积减少(P<0.05)；突触超微结构改善明显，突触数量增加(P<0.05)，突触相关因子突触蛋白、PSD-95表达上调(P<0.05)。Catwalk步态参数、脑梗死体积与突触超微结构改善有一致性。结论：电针曲池、足三里穴可改善MCAO大鼠运动障碍，其机制可能与上调突触相关因子的表达，改善突触可塑性有关。     

Influence of coronary stenosis location on diagnostic performance of machine learning-based fractional flow reserve from CT angiography

BackgroundCompared with invasive fractional flow reserve (FFR), coronary CT angiography (cCTA) is limited in detecting hemodynamically relevant lesions. cCTA-based FFR (CT-FFR) is an approach to overcome this insufficiency by use of computational fluid dynamics. Applying recent innovations in computer science, a machine learning (ML) method for CT-FFR derivation was introduced and showed improved diagnostic performance compared to cCTA alone. We sought to investigate the influence of stenosis location in the coronary artery system on the performance of ML-CT-FFR in a large, multicenter cohort.MethodsThree hundred and thirty patients (75.2% male, median age 63 years) with 502 coronary artery stenoses were included in this substudy of the MACHINE (Machine Learning Based CT Angiography Derived FFR: A Multi-Center Registry) registry. Correlation of ML-CT-FFR with the invasive reference standard FFR was assessed and pooled diagnostic performance of ML-CT-FFR and cCTA was determined separately for the following stenosis locations: RCA, LAD, LCX, proximal, middle, and distal vessel segments.ResultsML-CT-FFR correlated well with invasive FFR across the different stenosis locations. Per-lesion analysis revealed improved diagnostic accuracy of ML-CT-FFR compared with conventional cCTA for stenoses in the RCA (71.8% [95% confidence interval, 63.0%–79.5%] vs. 54.8% [45.7%–63.8%]), LAD (79.3 [73.9–84.0] vs. 59.6 [53.5–65.6]), LCX (84.1 [76.0–90.3] vs. 63.7 [54.1–72.6]), proximal (81.5 [74.6–87.1] vs. 63.8 [55.9–71.2]), middle (81.2 [75.7–85.9] vs. 59.4 [53.0–65.6]) and distal stenosis location (67.4 [57.0–76.6] vs. 51.6 [41.1–62.0]).ConclusionIn a multicenter cohort with high disease prevalence, ML-CT-FFR offered improved diagnostic performance over cCTA for detecting hemodynamically relevant stenoses regardless of their location.     

Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults

Background and aimsSome amino acids (AAs) may be associated with type 2 diabetes (T2DM). This study aimed to determine the associations of individual AAs with the development of T2DM in rural Chinese adults.Methods and resultsA cohort study of 1199 individuals aged 18 years or older was conducted from 2006 to 2008 in a rural community of Deqing, China, a repeated survey was done in 2015 and data linkage with the electronic health records system was performed each year for identifying new T2DM cases. A high-performance liquid chromatography approach was used to measure the baseline serum concentrations of 15 AAs. Cox proportional hazards models were used to examine the associations between AAs and the risk of incident T2DM. A total of 98 new T2DM cases were identified during the follow-up of 12 years on average. Among 15 AAs, proline was associated with an increased risk of incident T2DM after adjusted for age, sex, body mass index, fasting plasma glucose, family history of T2DM, smoking status, alcohol use, and history of hypertension, the adjusted hazard ratio for 1-standard deviation increment was 1.20 (95% confidence interval: 1.00, 1.43). The association tended to be more marked in subjects younger than 60 years and overweight/obese subjects. Among participants without hypertension, proline and phenylalanine were associated with an increased risk of incident T2DM, while aspartic acid was associated with a decreased risk.ConclusionSerum proline was associated with the risk of incident T2DM in rural Chinese adults and might be a potential predictor.     

Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling

Voltage‐gated Ca²⁺ (Ca_V) channels are crucial for neuronal excitability and synaptic transmission upon depolarization. Their properties in vivo are modulated by their interaction with a variety of scaffolding proteins. Such interactions can influence the function and localization of Ca_V channels, as well as their coupling to intracellular second messengers and regulatory pathways, thus amplifying their signaling potential. Among these scaffolding proteins, a subset of PDZ (postsynaptic density‐95, Drosophila discs‐large, and zona occludens)‐domain containing proteins play diverse roles in modulating Ca_V channel properties. At the presynaptic terminal, PDZ proteins enrich Ca_V channels in the active zone, enabling neurotransmitter release by maintaining a tight and vital link between channels and vesicles. In the postsynaptic density, these interactions are essential in regulating dendritic spine morphology and postsynaptic signaling cascades. In this review, we highlight the studies that demonstrate dynamic regulations of neuronal Ca_V channels by PDZ proteins. We discuss the role of PDZ proteins in controlling channel activity, regulating channel cell surface density, and influencing channel‐mediated downstream signaling events. We highlight the importance of PDZ protein regulations of Ca_V channels and evaluate the link between this regulatory effect and human disease.     

Sex-discrete role of depressive symptomatology on 10-year first and recurrent cardiovascular disease incidence: results from ATTICA and GREECS prospective studies

ObjectiveThe sex-specific effect of depressive symptomatology on 10-year first and recurrent cardiovascular disease (CVD) events was evaluated.MethodsThe Greek samples from ATTICA (2002-2012, n = 845 free-of-CVD subjects) and GREECS (2004-2014, n = 2,172 subjects with acute coronary syndrome (ACS)) prospective epidemiological studies with baseline psychological assessments were used for the first and the recurrent event, respectively. Depressive symptomatology was assessed at baseline, through Zung Self-Rating Depression Scale in the ATTICA study, and through the Center for Epidemiological Studies-Depression scale in the GREECS study.ResultsACS as well as free-of-CVD women scored significantly higher for depressive symptomatology. Men scored higher than women against first (19.7% vs. 11.7%) and subsequent CVD events (38.8% vs. 32.9%). In participants with depressive symptoms man-to-woman first and recurrent CVD event rate ratio was below 1, confirming that depressive women were more likely to have a CVD event than depressive men. Multiadjusted analysis revealed that depressive symptomatology had an independent aggravating effect on the first (hazard ratio (HR) = 2.72, 95% confidence interval (95% CI) 1.50, 9.12) and recurrent (HR = 1.31, 95% CI 1.01, 1.69) CVD events only in women. Mediation analysis in women revealed that 35% (23%, 44%) of excess first-CVD-event risk of depressive symptoms was attributed to conventional risk factors. The respective number for recurrent CVD events was 46% (23%, 53%); different patterns of ranking regarding the mediating effect corresponding to each adjustment factor were observed.ConclusionsThe present work augments prior evidence that psychological stressors possess important drivers of CVD onset and progression mainly in women, while it gives rise to research toward unidentified paths behind this claim.     

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model(MCAO) and paired associated magnetic stimulation(PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m~2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval No. 201802173 S) on March 3, 2018.