Association between abnormal default mode network activity and suicidality in depressed adolescents.

BACKGROUND: Suicide is the second leading cause of death among 15- to 29-year-olds in China, and 60 % of suicidal patients have a history of depression. Previous brain imaging studies have shown that depression and suicide may be associated with abnormal activity in default mode network (DMN) regions. However, no study has specifically investigated the relationship between DMN functional activity and suicidal behavior in depressed individuals. Therefore, in the present study, we directly investigated features of DMN brain activity in adolescent patients with histories of depression and attempted suicide. METHODS: A total of 35 sex- and age-matched suicidal depressed patients were compared with 18 non-suicidal depressed patients and 47 healthy controls. We explored functional activity changes in DMN regions that could be associated with suicidal behavior by comparing resting-state functional magnetic resonance imaging (rs-fMRI) signals using independent component analysis (ICA). Scores on six clinical scales that measure depression severity (Hamilton Depression Scale (HDRS) and Beck Depression Inventory (BDI)) and suicidal traits (Barratt Impulsiveness Scale (BIS-11), Suicide Attitude Questionnaire (SAQ), Beck Hopelessness Scale (BHS), and Scale for Suicide Ideation (SSI)) were compared in the three groups. RESULTS: Compared with the healthy controls, all of the evaluated depressed patients showed increased functional connectivity in select DMN regions. The suicidal patients showed increased connectivity in the left cerebellum and decreased connectivity in the right posterior cingulate cortex (PCC), whereas the non-suicidal depressed patients showed increased connectivity in the left superior frontal gyrus, left lingual gyrus and right precuneus and decreased connectivity in the left cerebellum. Compared to the non-suicidal patients, the suicidal patients showed increased connectivity in the left cerebellum and the left lingual gyrus and decreased connectivity in the right precuneus. No differences in the scores of any clinical scales were found between the suicidal and non-suicidal depressed patients. CONCLUSIONS: Collectively, our results highlight the importance of the DMN in the pathophysiology of depression and suggest that suicidal behavior in depressed adolescents may be related to abnormal functional connectivity in the DMN. In particular, abnormal connectivity in the PCC/precuneus and left cerebellum might be a predictor of suicidal behavior in depressed adolescent patients.

The cytoptrotection of small intestinal submucosa-derived gel in HL-1 cells during hypoxia/reoxygenation-induced injury.

Small intestinal submucosa (SIS)-derived gel injected into infarcted myocardium has been shown to promote repair and regeneration after myocardial infarction (MI); however, the specific impact of SIS gel on cardiomyocytes remained unknown. The aim of this study was to characterise SIS gel function in hypoxia-reoxygenation (H/R)-induced cardiomyocyte damage and its potential mechanism. HL-1 cardiomyocytes seeded on SIS matrix-coated plates, SIS gel, and uncoated plates were subjected to H/R, cell viability, apoptosis, expression of caspase-3, Bcl-2, and Bax were investigated. SIS gel and SIS matrix as coating substrates markedly improved cell viability, preventing cell apoptosis compared with uncoated plates, with SIS gel yielding the best cytoprotective effects. SIS gel down-regulated expression of pro-inflammatory cytokines (TNF-α, CCL2, and IL-6) by inhibiting the JNK-mitogen-activated protein kinase (MAPK)/NF-κB pathways. Furthermore, SIS gel protected cardiomyocytes from apoptosis by activating protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK) pathways, and markedly up-regulated antiapoptotic Bcl-2 expression but inhibited that of proapoptotic Bax and c-caspase 3. Together, these findings show that SIS gel could decrease H/R-induced cell apoptosis through a mechanism potentially related to its ability to regulate expression of inflammatory cytokines and antiapoptosis signalling pathways to prevent cell apoptosis. Our findings thereby shed light on the mechanism related to SIS gel therapeutic efficacy for MI.

[The influence of early vascular rejection on late rejection in first cadaveric renal transplantation].

OBJECTIVE: To explore the influence of early completely reversal vascular rejection on late rejection. METHODS: The data of 1062 patients who received their first cadaveric transplants between May 1988 and March 2003 were analyzed respectively. The patients were divided into 2 groups: group with vascular rejection occurring within 1 month postoperatively (n = 45), and group without vascular rejection (n = 1017). Follow up was performed for at least 6 months. The influence of demographic characteristics (transplant age, sex), transplant variables (complement dependent cytotoxicity test, cold/warm ischemia time), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection,) were analyzed. RESULTS: There were no differences in the age at transplantation, sex, complement dependent cytotoxicity test, cold/warm ischemia time, immunosuppression agent protocol, and serum creatinine during follow-up between the recipients of these two groups. Late rejection, including acute interstitial rejection, borderline rejection, and chronic rejection, occurring one month after transplantation was 2.22% (1/45) in the vascular rejection group, significantly lower than that of the no vascular rejection group (12.59%, 128/1017, P = 0.034) CONCLUSION: Early completely reversal vascular rejection can reduce the rate of late rejection.

[Completely reversed acute rejection episodes do not influence the long-term renal allograft survival].

OBJECTIVE: To assess the influence of times and duration of acute rejection episodes and the effect of antirejection therapy in renal transplantation recipients on the long-term survival of renal allograft. METHODS: The clinical data of 946 patients who received renal transplantation were analyzed to analyze the survival of renal allograts in different conditions: times of rejection episode, time of onset of acute rejection, and effect of antirejection therapy by life table and Wilcoxon test, and to identify the risk factors through Cox regression analysis. RESULTS: During the follow-up with a range of 3 approximately 158 months acute rejection occurred in 172 patients. The 946 cases of kidney transplantation were divided into rejection free group (NAR, n = 774), one time rejection group (1AR, n = 159), and twice and more rejection group (2AR, n = 13) according to the times of rejection. The 1AR group was subdivided into completely reversed group (CAR) and incompletely reversed group (1AR). The 1AR cases were subdivided into early-stage rejection group (EAR, with episode within 90 days after transplantation, n = 112) and late-stage rejection group (LAR, with episode 90 days later transplantation, n = 47) according to the onset time of rejection episode. The five-year survival rate was 70.9% in the AR group (n = 172) and was 93.3% in the NAR group (P < 0.000 1). The ten-year survival rate of renal allografts was 29.8% in the AR group, and was 83.3% in the NAR group (P < 0.000 1). The 5-year survival rate of renal allograft was less than 30% in the 2AR group, significantly lower than those in the NAR and IAR groups (P < 0.000 1 and P< 0.003). The 5-year survival rate of renal allograft was 89.0% in the EAR group, significantly higher than that in the LAR group (48.9%, P < 0.000 1). The 8-year survival rate was 84.3% in the EAR group, significantly higher than that in the LAR group (32.1%, P < 0.000 1). Both the survival rates of renal allograft in the EAR and LAR groups were significantly lower than that in the NAR group (P = 0.025 and P < 0.000 1). The condition had been completely reversed in 95 patients and incompletely reversed in 54 patients, and failed to be improved in 10 patients out of the 159 cases in the IAR group after antirejection therapy. The 5-year survival rate of renal allograft was 93.9% in the CAR group, significantly higher than that in the IAR group (63.1%, P < 0.000 1) but not significantly different from that in the NAR group (P = 0.96). The 8-year survival rate of renal allograft was 89.2% in the CAR group, significantly higher than that in the IAR group (41.4%, P < 0.000 1) but not significantly different from that in the NAR group (P = 0.96). The time of rejection onset was not the main factor effecting survival rate of grafts. The main risk factor influencing the long-term survival of renal allograft was the therapeutic effect after the onset of rejection with a risk rate of 3.14. CONCLUSION: The acutely rejected renal allografts have poor long-term survival. The long-term survival rate of renal allograts with acute rejection that occurs only once and is completely recovered after antirejection therapy is not significantly different from that of the renal allografts in NAR group.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.