Search

Sorafenib, a multi-kinase inhibitor, is recommended as a new standard therapy for advanced hepatocellular carcinoma (HCC); however, it also exhibits severe cardiotoxicity and the toxicity mechanisms are not completely elucidated. Recent studies suggested that sorafenib-enhanced ROS may partially contribute to its anti-HCC effect, which implies that redox mechanism might also be involved in sorafenib's cardiotoxicity. In this study, we aimed to investigate if sorafenib is able to induce oxidative stress and how this may impair cellular functions in cardiomyocyte, ultimately accounting for its cardiotoxicity. Our results showed that in isolated rat hearts, sorafenib caused ventricular arrhythmias and left ventricular dysfunction, which were alleviated by the antioxidant N-(2-mercaptopropionyl)-glycine (MPG). In isolated ventricular myocytes, sorafenib increased diastolic intracellular Ca2+ levels, decreased Ca transients and the occurrence of Ca2+ waves. These changes were eliminated by MPG, CaMKII inhibitor KN-93 and the mitochondrial permeability transition pore (mPTP)inhibitor cyclosporin A (CsA). Moreover, the levels of oxidized and phosphorylated CaMKII were significantly increased. Sorafenib elevated ROS levels, which was reversed by CsA and MPG; additionally, sorafenib reduced the activity of mitochondrial complex III and augmented mitochondrial ROS production. In vivo rats treated with sorafenib exhibited a reduction of antioxidant defence and abnormal histological alterations including hypertrophy, increased fibrosis, disordered myofibrils and damaged mitochondria, which were protected by MPG. We conclude that sorafenib induces the disruption of Ca2+ homoeostasis and cardiac injury via enhanced ROS potentially through inhibiting mitochondrial complex III, the opening of mPTP and overactivating CaMKII. These results provide a potential strategy for preventing or reducing cardiotoxicity of sorafenib.

Background This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). Methods Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden’s Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. Results For Golden’s interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden’s Stroop RT disappeared, but differences in Golden’s Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. Conclusions Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.

Highlights • We provide the possible methods for psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai. As we mentioned: an effective PCI surely requires the two-pronged approaches, online and onsite psychotherapy are recommended ., Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.

Background. The cross-sectional study is aimed at investigating the relationship between cortisol, testosterone, and metabolic characteristics among male schizophrenics. Methods. 174 patients were grouped based on their risk of metabolic syndrome (MetS) into the non-MetS, high-risk-MetS (HR-MetS), or MetS groups. Metabolic indices (body mass index (BMI), mean arterial pressure (MAP), cholesterol, triglyceride, and fasting blood glucose (FBG)) were associated with cortisol and testosterone levels using correlation analysis. Multiple linear regression analysis was used to associate the correlations between the WHO Quality of Life–BREF (WHOQOL–BREF) score and the five metabolic indices. Results. The WHOQOL–BREF score for the non-MetS group significantly differed from the scores of the HR-MetS and MetS groups. The triglyceride level was positively correlated with the cortisol level, while all five metabolic indices were negatively correlated with testosterone level. Stepwise regression analysis produced a model predicting WHOQOL–BREF scores with four variables including MAP, intelligence quotient (IQ), FBG, and age. The correlation analysis then showed that there was a weak linear correlation between the testosterone level and all five metabolic indices. Conclusions. Among the five metabolic indices, the risks of hypertension and hyperglycemia are correlated with the quality of life in male schizophrenics rather than those of obesity or hyperlipidemia.

The neural networks that constitute corticostriatothalamocortical circuits between prefrontal cortex and subcortical structure provide a heuristic framework for bridging gaps between neurocircuitry and executive dysfunction in attention deficit hyperactivity disorder (ADHD). “Cool” and “Hot” executive functional theory and the models of dual pathway are supposed to be applied within the neuropsychology of ADHD. The theoretical model elaborated response inhibition and delayed gratification in ADHD. We aimed to review and summarize the literature about the circuits on ADHD and ADHD-related comorbidities, as well as the effects of neurocircuitry on the executive dysfunction in ADHD.

The neurocircuitries that constitute the cortico-striato-thalamo-cortical (CSTC) circuit provide a framework for bridging gaps between neuroscience and executive function in attention deficit hyperactivity disorder (ADHD), but it has been difficult to identify the mechanisms for regulating emotional problems from the understanding of ADHD comorbidity with disruptive behavior disorders (DBD). Research based on “cool” and “hot” executive functional theory and the dual pathway models, which are thought of as applied response inhibition and delay aversion, respectively, within the neuropsychological view of ADHD, has shed light on emotional responding before and after decontextualized stimuli, while CSTC circuit-related domains have been suggested to explain the different emotional symptoms of ADHD with or without comorbid DBD. This review discusses the role of abnormal connections in each CSTC circuit, especially in the emotion circuit, which may be responsible for targeted executive dysfunction at the neuroscience level. Thus, the two major domains – abstract thinking (cool) and emotional trait (hot) – trigger the mechanism of onset of ADHD.

The prefrontal cortex is the superlative structure of brain that needs the longest developmental and maturational duration that highlights the region of attention deficit hyperactivity disorder (ADHD) in neuroimaging studies. Prefrontal cortex functions generate enormously complex and its abundant feedback neurocircuitries with subcortical structures such as striatum and thalamus established through dual neural fibers. These microneurocircuitries are called corticostriatothalamocortical (CSTC) circuits. The CSTC circuits paly an essential role in flexible behaviors. The impaired circuits increase the risk of behavioral and psychological symptoms. ADHD is an especial developmental stage of paediatric disease. It has been reported that the CSTC circuits dysfunctions in ADHD are related to homologous symptoms. This study aimed to review the symptoms of ADHD and discuss the recent advances on the effects of the disease as well as the new progress of treatments with each circuit.