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Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca2+ transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.

BackgroundPrevious studies have identified the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on cravings of patients with methamphetamine use disorder (MUD). However, the mechanism underlying the treatment effect remains largely unknown. A potential candidate mechanism could be that rTMS over the dorsolateral prefrontal cortex (DLPFC) modulates the attention bias to methamphetamine-related cues. The purpose of this study is therefore to determine the modulation of rTMS on methamphetamine-related attention bias and the corresponding electrophysiological changes.MethodsForty-nine patients with severe MUD were included for analysis. The subjects were randomized to receive the active intermittent theta-burst stimulation (iTBS) or sham iTBS targeting DLPFC for 20 sessions. Participants performed the Addiction Stroop Task before and after the treatment while being recorded by a 64-channel electroencephalogram. Baseline characteristics were collected through the Addiction Severity Index.ResultsPost-treatment evaluations showed a reduced error rate in discriminating the color of methamphetamine words in the active iTBS group compared with the sham iTBS group. Following rTMS treatment, we found the significant time-by-group effect for the N1 amplitude (methamphetamine words > neutral words) and P3 latency (methamphetamine words > neutral words). The change of N1 amplitude was positively correlated with cravings in the active group. Moreover, reduced power of neural oscillation in the beta band, manifesting at frontal central areas, was also found in the active group.ConclusionThis study suggests that attention bias and the beta oscillation during the attentional processing of methamphetamine words in patients with MUD could be modulated by iTBS applied to left DLPFC.

Objectives The purpose of the study was to investigate whether Group Music Therapy (GMT) could enhance the treatment motivation and change the negative emotion among female patients with methamphetamine use disorder in a randomized clinical trial. Methods Participants ( N = 60) were randomized to the group of GMT combined with treatment as usual (TAU) or the group with TAU only. Questionnaire of Motivation for Abstaining from Drugs was used to measure the motivation for abstaining from drugs of the female patients. And Self-Rating Depression Scale and Self-Rating Anxiety Scale were used to measure negative emotion of participants. The measurements were conducted at T0 (baseline), T1 (post 13 sessions of intervention) and T2 (3-month follow-up after T1) by the independent trained researcher. Results The postintervention and 3-month follow-up results according to the intention-to-treat principle indicated that GMT + TAU intervention showed significantly positive group-by-time effect on the scores of the subscale-tending to rehabilitation-internal motivation ( p = 0.01) and avoiding abuse-external motivation ( p = 0.04). In 3-month follow-up, total scores of the questionnaire of motivation for abstaining from drugs ( p = 0.02), scores of avoiding abuse-internal motivation subscale ( p = 0.05), and scores of confidence of abstaining from drugs subscale ( p = 0.01) in GMT + TAU were also presented with significantly positive group x time effect. The changes of total score of Questionnaire of Motivation for Abstaining from Drugs (from baseline to 3-month follow-up) was significantly positive association with the changes of scores of SAS in GMT + TAU group ( r = −0.55, p = 0.00). Conclusions The present study suggests that GMT could be used as an effective treatment strategy to enhance treatment motivation of female patients with methamphetamine use disorder.

Summary Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020)., Graphical abstract, Highlights • Protocol for applying repetitive TMS to decrease the craving and relapse • Accurate positioning is one of the crucial steps of repetitive TMS treatment • The treatment process requires continuous attention to the patient’s response, Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics.

Animal studies have reported the brain glutamatergic dysfunction in substance dependence. However, proton magnetic resonance spectroscopy (1H-MRS) studies of glutamate in substance-dependent patients published contradicting results. In order to investigate the characteristics of brain glutamatergic alterations in substance-dependent patients, we conducted systematic reviews and meta-analyses of 1H-MRS studies that have investigated the glutamate, glutamine, and Glx (glutamate + glutamine) concentration in substance-dependent patients. Multiple databases were searched until Sep 10, 2020. Twenty-nine studies comprising 982 patients and 787 controls were included. There was significantly decreased glutamate level in dorsolateral prefrontal cortex in patients compared with controls. Higher glutamate levels in medial prefrontal cortex and basal ganglia region were also demonstrated in patients compared with controls. Subgroup analyses based on the substance type and abstinence period (short vs medium-term abstinence period) were performed. The results revealed Glx and glutamate concentrations in all investigated brain regions were not different in patients with any types of substance dependence compared with controls. The abstinence period had no effect on the glutamate levels. In summary, substance dependence is associated with glutamatergic dysfunction of prefrontal cortex and basal ganglia. Present findings partially support the hypothesis that addiction is associated with abnormal brain glutamatergic neurotransmission.

Inflammation is closely related to the pathogenesis and prognosis of cardiovascular disease (CVD). Interleukin-37 (IL-37), an anti-inflammatory IL-1 family cytokine, shifts cytokine expression from pro- to anti-inflammation via regulation of macrophage polarization and lipid metabolism. In macrophages, IL-37 functions through both intracellular and extracellular pathways to regulate the activity of NF-kB and PTEN as well as the expression of cytokines, including IL-1β, IL-6, and IL-10. Moreover, IL-37 levels are increased in the serum of patients with heart failure, atherosclerosis, and acute coronary syndrome with no evidence of anti-inflammatory effects. However, transgenic overexpression of IL-37 improves cardiac infarct and attenuates atherosclerosis plaque expansion. Hence, it is worthwhile to investigate the precise mechanism and role of IL-37 in the pathogenesis of CVD, which may provide deeper understanding of the inflammatory response in this context. This review summarizes the regulatory role of IL-37 in systematic inflammation induced by CVD and highlights recent advancements in the clinical application of IL-37 as a therapeutic agent or biomarker for diagnosis of CVD.

Background: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. Methods: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). Findings: The three real TBS groups had more craving decrease effect than the sham group (p

Background Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated with the colon cancer 1 (MACC1) predicted poor prognosis of GC and promoted tumor cells proliferation and invasion. In this study, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 reversed this resistance. Methods The effect of trastuzumab and glycolysis inhibitor combination on cell viability, apoptosis, and cell metabolism was investigated in vitro using established trastuzumab-resistant GC cell lines. We assessed the impact of trastuzumab combined with oxamate on tumor growth and metabolism in an established xenograft model of HER2-positive GC cell lines. Results Here, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 in trastuzumab-resistant cells reversed this resistance. Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects. Moreover, when the PI3K/AKT signaling pathway was inhibited, the effects of MACC1 on resistance and glycolysis were diminished. Our findings indicated that MACC1 promoted the Warburg effect mainly through the PI3K/AKT signaling pathway, which further enhanced GC cells trastuzumab resistance. Conclusions Our results indicate that co-targeting of HER2 and the Warburg effect reversed trastuzumab resistance in vitro and in vivo, suggesting that the combination might overcome trastuzumab resistance in MACC1-overexpressed, HER2-positive GC patients. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0302-1) contains supplementary material, which is available to authorized users.

The education contents of different engineering majors have varied greatly, and each specific major has its own discretion of professional curriculum establishment. How to objectively probe the advances of majors and make right use of this decision-making power is an essential link in the comprehensive education reform of engineering majors. The shifts of professional education focus in engineering majors were obtained by analyzing related bibliometrics. First a hierarchical classification of professional literature related to a specific major is formed, and the literature number of each group in the hierarchical classification is recorded in a chronological sequence, then the relationship between the literature number and time is established by mathematical regressions, subsequently the drifting pattern of key knowledge points within the major being deduced in the form of quantitative models, which enable us to objectively discover shifts of education focus in the engineering major and sensibly facilitate arranging curriculums and amending/compiling textbooks, modulating teaching and experiments. This method was applied in the mineral processing

The snake-like robot needs to adapt to complex environment, in order to reach the target point safely and collisionless, necessary obstacle avoidance strategy is of vital importance. In this paper, laser radar and ultrasonic sensors are used to detect the surrounding environment, and then information fusion method based on TS fuzzy neural network is adopted to integrate the collected information, which provides the necessary condition for obstacle avoidance research of the snake-like robot. Experiments show that the snake-like robot can successfully avoid obstacles to reach the target point after training of the fuzzy neural network.