Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder.

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

Advantage of surgical intensive care unit (SICU) predominant by cardiothoracic surgeons in multiple trauma management in a primary hospital.

PURPOSE: It is a challenge for the primary hospitals to manage multiple trauma patients. In this article, we explored the advantage of establishing a surgical intensive care unit (SICU) predominant by cardiothoracic surgeons in the early management of multiple trauma. METHODS: This was a retrospective study and patients with multiple trauma in our hospital were collected and divided into two groups, based on time period and treat modes: group A (retrospective observation group) where patients were treated with the traditional treatment mode from January 2017 to December 2017 and group B (study group) where patients were treated in the SICU predominant by cardiothoracic surgeons from January 2018 to December 2018. Clinical data including demographics, injury severity score (ISS), causes of injury, time intervals from reception to entering SICU or operating room and mortality three days after injuries were collected. Data were analyzed by SPSS 20.0 software. Categorical variables were presented as number and/or frequency and continuous variables as mean ± SD. RESULTS: Altogether 406 patients were included in this study, including 217 patients in group A and 189 patients in group B. General data between the two groups revealed no significant difference: mean age (years) (35.51 ± 12.97 vs. 33.62 ± 13.61, p = 0.631), gender distribution (mean/female, 130/87 vs. 116/73, p = 0.589) and ISS (15.92 ± 7.95 vs. 16.16 ± 6.89, p = 0.698). Fall from height were the dominant mechanism of injury, with 135 cases in group A (71.4%) and 121 cases in group B (55.8%), followed by traffic accidents. Injury mechanism showed no significant differences between two groups (p = 1.256). Introduction of the SICU significantly improved the care of trauma patients, regarding speed and mortality. Time intervals between reception and entering SICU or operating room was (108.23 ± 6.72) min and (45.67 ± 7.96) min in group A and B, respectively (p = 0.001). Mortality three days after injuries was 13.89% and 5.53% in group A and B, respectively (p = 0.005). CONCLUSION: Establishing a SICU predominant by cardiothoracic surgeons can reduce the early mortality rates in multiple trauma patients.

SENP6 induces microglial polarization and neuroinflammation through de-SUMOylation of Annexin-A1 after cerebral ischaemia-reperfusion injury.

BACKGROUND: Previous data have reported that Sentrin/SUMO-specific protease 6 (SENP6) is involved in ischaemic brain injury and induces neuronal apoptosis after cerebral ischaemia, but the role of SENP6 in microglia-induced neuroinflammation and its underlying mechanism remain poorly understood. This research systematically explored the function and potential mechanism of SENP6 in microglia-induced neuroinflammation after ischaemic stroke. RESULTS: We first identified an increased protein level of SENP6 in microglia after cerebral ischaemia. Then, we demonstrated that SENP6 promoted detrimental microglial phenotype polarization. Specifically, SENP6-mediated de-SUMOylation of ANXA1 targeted the IκB kinase (IKK) complex and selectively inhibited the autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression. In addition, downregulation of SENP6 in microglia effectively reduced cocultured neuronal damage induced by ischaemic stroke. More importantly, we employed an AAV-based technique to specifically knockdown SENP6 in microglia/macrophages, and in vivo experiments showed that SENP6 inhibition in microglia/macrophages notably lessened brain ischaemic infarct size, decreased neurological deficit scores, and ameliorated motor and cognitive function in mice subjected to cerebral ischaemia surgery. CONCLUSION: We demonstrated a previously unidentified mechanism by which SENP6-mediated ANXA1 de-SUMOylation regulates microglial polarization and our results strongly indicated that in microglia, inhibition of SENP6 may be a crucial beneficial therapeutic strategy for ischaemic stroke.

The Clinical Significance of Changes in Serum New Cytokine CYTL1 in Patients with Knee Osteoarthritis.

OBJECTIVE: The present study aims to investigate the clinical significance of changes in the expression of new cytokine-like 1 (CYTL1) in the serum of patients with knee osteoarthritis (KOA). METHODS: A total of 182 patients with KOA, including 84 males and 98 females aged 39-86 with an average age of 66.4 ± 9.7 and an average body mass index (BMI) of 24.9 ± 2.4 kg/m2, were enrolled in the study. The patients were divided into three subgroups: the grade II subgroup (n = 23), grade III subgroup (n = 63), and grade IV subgroup (n = 96) based on severity, as calculated by the Kellgren and Lawrence (K&L) classification system. In addition, 152 volunteers from our health center who came in for physical examination were selected as the control group, including 70 males and 82 females aged 37-82 with an average age of 63.4 ± 9.5 and an average BMI of 24.8 ± 2.2 kg/m2. An enzyme-linked immunosorbent assay was adopted to detect the serum CYTL1 levels, and the correlation between CYTL1 and the severity of KOA was analyzed. RESULTS: The serum level of CYTL1 was significantly lower in the KOA group than in the control group (P < 0.05). In the KOA group, the difference in the serum level of CYTL1 was statistically significant between the subgroups and decreased significantly with an increase in the severity of the disease (F = 54.826, P < 0.001). Therefore, the serum level of CYTL1 was correlated with the severity of the disease, as determined by the K&L classification system (r = -0.613, P < 0.001). CONCLUSION: The serum levels of CYTL1 are strongly correlated with the severity of the disease in patients with KOA and could be a new therapeutic target for KOA.

Effects of short-term cognitive-coping therapy on resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) tends to be treatment refractory. Recently, cognitive-coping therapy (CCT) for OCD is reported to be an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. Here, the effects of CCT on OCD and the resting-state brain function were investigated. METHODS: Fifty-nine OCD patients underwent CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Before and after a 4-week treatment, Yale-Brown obsessive-compulsive scale (Y-BOCS) was evaluated and resting-state functional magnetic resonance imaging (rs-fMRI) was scanned. RESULTS: Compared with the baseline, significant reduction of Y-BOCS scores was found after four-week treatment (p < .001) in groups of CCT and pCCT, not in pharmacotherapy. Post-treatment Y-BOCS scores of CCT group and pCCT group were not different, but significantly lower than that of pharmacotherapy group (p < .001). Compared with pretreatment, two clusters of brain regions with significant change in amplitude of low-frequency fluctuation (ALFF) were obtained in those who treated with CCT and pCCT, but not in those who received pharmacotherapy. The ALFF in cluster 1 (insula, putamen, and postcentral gyrus in left cerebrum) was decreased, while the ALFF in cluster 2 (occipital medial gyrus, occipital inferior gyrus, and lingual gyrus in right hemisphere) was increased after treatment (corrected p < .05). The changes of ALFF were correlated with the reduction of Y-BOCS score and were greater in remission than in nonremission. The reduction of the fear of negative events was correlated to the changes of ALFF of clusters and the reduction of Y-BOCS score. CONCLUSIONS: The effectiveness of CCT for OCD was related to the alteration of resting-state brain function-the brain plasticity. TRIAL REGISTRATION: ChiCTR-IPC-15005969.

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma.

Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro, NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction. Cisplatin could activate PI3K-Akt-mTOR pathway activity in early times, whereas, NVP-BEZ235 could inhibit PI3K-Akt -mTOR pathway activity all the times alone or combined with cisplatin. What's more, NVP-BEZ235 could switch function of autophagy induced by cisplatin to synergize cisplatin sensitivity. In vivo, pronounced decrease in tumor cell proliferation and increase in apoptosisin combination-treated mouse xenograft models compared with cisplatin or NVP-BEZ235 treated models. All these results suggest NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS.

Effectiveness of cognitive-coping therapy and alteration of resting-state brain function in obsessive-compulsive disorder.

BACKGROUND: Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT. PATIENTS AND METHODS: Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment. RESULTS: For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (P<0.001), but no group difference was observed. No differences in amplitude of low-frequency fluctuation (ALFF) values were found between CCT and pCCT either pre- or post-treatment. Compared to controls, ALFF in OCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected P<0.05). The ALFF in those regions was not significantly correlated to the severity of OCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared. LIMITATIONS: The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks. CONCLUSIONS: Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved.