RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro / 南方医科大学学报

OBJECTIVE@#To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion.@*METHODS@#Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting.@*RESULTS@#The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001).@*CONCLUSION@#Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.

A correlation study on depression and life events of patients with primary sjogren syndrome / 中华行为医学与脑科学杂志

Objective To explore the relationship between life events and depression of patients with primary sjgren's syndrome (PSS).Methods 80 patients with PSS complicating depressive disorder were tested by self-rating depression scale(SDS) and life event scale (LES),and compared with the control group including 80 PSS patients with non-depressive disorder matched with age and sex.Then the correlation between SDS and LES were analyzed.Results The total score of life events (32.72 ± 13.93),the score of negative life events (24.36 ±11.24),the score of SDS(58.60 ± 16.78) and the frequency of life events(91.3％) in the research group were higher than those in control group(P ＜ 0.05),but the positive life events score (7.15 ± 5.84) was lower than that in control group (9.76 ± 7.29),and there was statistically significant difference between the two groups (P ＜ 0.05),there were more negative life events,especially on the aspects of family,work and study in the research group.There was positive correlation among the negative life events score,total score of life events and SDS score in the research group(P＜ 0.01),meanwhile,negative correlation was revealed between the score of positive life events and SDS score in the research group(P ＜ 0.05).Conclusion Patients with PSS complicating depressive disorder experienced more negative life events which play an important role in depression of patients with PSS.

The investigation and related factors analysis for the depression of patients with primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To survey the prevalence and the related factors of depression in patients with primary Sj(o)gren's syndrome (pSS),and provide references for early mental intervention.Methods The depression state of 217 patients with pSS was screened with self-rating depression scale (SDS) first and then assessed by Hamilton depression scale (HAMD,17 index).The prevalence of depression was determined based on the diagnosis of psychiatrist based on the 3rd edition of Chinese classification of mental disorders (CCMD Ⅲ).The personality was evaluated by Eysenck personality questionnaire (EPQ),and the life events were questionnaired by life events scale (LES).The general condition was analyzed by self-designed questionnaire.Finally,step-wise multiple factor regression analysis was carried out to determine the risk factors that best accounted for the depression.Results The prevalence rate of depression in patients with pSS was 39.2％ (85/217).There were 5 factors entered the regression equation by multifactor regression analysis.They were severe pain,concerns of doctor and nurse,known of the fact by patients,adverse life events,and neuroticism of EPQ,and the concern of doctor and nurse was negatively correlated.Conclusion More attention from clinicians should be paid to the depression of pSS.Patients with severe pain,lack of attention from doctors and nurses,known of the disease itself,adverse life events and neurotic personality traits are factors related with depression.Recognizing the risk factors early can provide guidance for early psychological intervention.

A 3-year study of patients with Kawasaki's disease complicated with coronary artery lesion / 中华风湿病学杂志

Objective To investigate the prognosis of patients with Kawasaki's disease complicated with coronary artery lesion and to provide evidence for diagnosis and treatment of these patients. Methods This study was conducted during January 2002 to June 2007. All patients diagnosed as Kawasaki's disease complicated with coronary artery lesions were from the Affiliated Hospital of Guilin Medical College, the Second People's Hospital of Guangxi Province and Guilin Women and Childrens' Hospital. All cases were echocardiogram examined in month 3, 6, 12, 24 and 36 in the purpose of observing the morphology of coronary artery. The study subjects were re-categorized to the groups of mild, moderate dilatation of coronary artery and giant coronary aneurysm, based on the severity of coronary artery lesion. The results of these results of the three groups were compared. Results Eighty-four cases in the mild group, 27 cases in the moderate group and 8 cases in the giant coronary aneurysm. The recovery cases were 23 (27%), 3 (11%) and 0 in the 3 groups respectively at month 3. The above numbers were 44 (52%), 8 (30%) and 0 respectively at month 6.The numbers were 69(82%), 13 (48%) and 1 (13%) at month 12. The numbers were 78 (93%), 19 (70%), 3 (38%) at month 24. The numbers were 82(98%), 20(74%) and 4(50%) at month 36. Thirteen patients were treated with adenosine-triphosphate (ATP) stress echocardiography examiantion, 5 patients were evaluated by coronary angiography,and 4 patients were tested by 64-slice CT coronary reconstruction. Part of the patients were found to have coronary stenosis or occlusion. Conclusion Patients of Kawasaki's disease often have concurrent coronary artery lesions. Patients with mild dilatation of the coronary artery are the most commonly seen and have the best prognosis. On the contrast, patients with giant coronary aneurysm are the lest common situation and is the worst in prognosis. Part of them will develop coronary artery stenosis or occlusion in late stage which may lead to ischemic heart disease. We should stress on close follow-up of patients with Kawasaki's disease complicated with coronary artery lesion. Appropriate and timely treatment will increase their clinical outcomes.

Observation on low-dose intravenous cyclophosphamide combined with standard-dose hormone in treatment of old patients with systemic lupus erythematosus / 中国基层医药

ObjectiveTo assess the efficacy of low-dose intravenous cyclophosphmide (IV CTX) in treatmerit of old patients with systemic lupus erythematosus(SLE).MethodsTwenty-three old patients with newly diagnosed, untreated SLE were included.Patients received 3 times fortnightly IV CTX pulses at a fixed dose of 400mg followed by 3 monthly pulses.All patients were orally administered 0.8mg/kg of prednisone.The changes of the indexes were observed before and after 12 weeks treatment including the scores of SLE disease activity index(SLEDAI) and the levels of C3, C4 ,24-hour urinary protein and anti-dsDNA antibody.ResultsAmong 23 patients, 19 were followed up to 24 weeks, SLEDAI 4 weeks after treatment were all significantly lower than those before the treatment (P ＜0.01).At week 8, SLEDAI continued to decrease(P ＜0.05).At week 4,the level of urine protein, the levels of complements C3 and C4 and ds-DNA decreased significantly compared with that before the treatment (P ＜0.05).ConclusionIntensive low-dose CTX plus prednisone was effective in newly diagnosed, untreated old patients with SLE, and could reduce adverse effect.