CXCR4 antagonism in combination with IDO1 inhibition weakens immune suppression and inhibits tumor growth in mouse breast cancer bone metastases.

PURPOSE: To investigate whether inhibition of the CXCL12/CXCR4 axis or IDO1 could produce antitumor effects in a metastasized breast cancer immunocompetent animal model. METHODS: Breast cancer metastasis models were established in mice. CXCR4 inhibitor and IDO1 inhibitor were used to evaluate the anticancer effects. RESULTS: Combination treatment using the CXCR4 antagonist AMD3465 and the IDO1 inhibitor D1MT successfully delayed the progression of breast cancer bone metastases. AMD3465 reduced the number of intratumoral regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs), while D1MT facilitated the antitumor effects of intratumoral CD8+ T-cells. IDO1 inhibition elevated the expression of perforin, granzyme-B, and IFN-γ in CD8+ T-cells, and AMD3465 treatment weakened the potential immune suppressive effects of Tregs and MDSCs. As a result, combination treatment significantly prolonged tumor-bearing mouse survival in two metastasis models, and these antitumor effects relied on overexpression of indoleamine 2, 3-dioxygenase 1 (IDO1), an enzyme that modulates the immune response and impairs immune attack in ovarian cancers CXCR3+ CD8+ cytotoxic T-cell function. CONCLUSION: The current study provides preclinical evidence that AMD3465 treatment in combination with IDO1 inhibition may be a promising therapeutic regimen for refractory metastasized breast cancers.

The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer's disease.

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.

Development and psychometric properties of an informant assessment scale of theory of mind for adults with traumatic brain injury.

Impairment of theory of mind (ToM) is a common phenomenon following traumatic brain injury (TBI) that has clear effects on patients' social functioning. A growing body of research has focused on this area, and several methods have been developed to assess ToM deficiency. Although an informant assessment scale would be useful for examining individuals with TBI, very few studies have adopted this approach. The purpose of the present study was to develop an informant assessment scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item scale was developed following a literature review, interviews with patient informants, consultations with experts, item analysis, and exploratory factor analysis (EFA). The following three common factors were extracted: social interaction, understanding of beliefs, and understanding of emotions. The psychometric analyses indicate that the scale has good internal consistency reliability, split-half reliability, test-retest reliability, inter-rater reliability, structural validity, discriminate validity and criterion validity. These results provide preliminary evidence that supports the reliability and validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI.

[Depression status of the family member and its influencing factors in the patient with mental disorder caused by cerebral trauma: 245 cases analysis].

OBJECTIVE: To determine the family member's depression status and its influencing factors in the patient with mental disorder caused by cerebral trauma. METHODS: The self-designed information questionnaire and self-rating depression scale (SDS) were used to investigate 245 family members' depression conditions. On the basis of SDS score index, all cases were divided into depression group and non-depression group. The data were analyzed by the univariate analysis and multiple factors regression analysis. RESULTS: In the 245 family members, 117 family members had different degrees of depressive symptoms including 68 with mild depression, 42 with moderate depression, and 7 with severe depression. In the multiple factors regression analysis, genetic relationship, personality characteristics and payment method were the main influencing factors of the depression status. CONCLUSION: Much attention should be paid to the family member's depression condition of the patient with mental disorder caused by cerebral trauma through specific psychological intervention.

[Application of WAIS-RC short forms and adult intelligence disability scale in mental impairment assessment].

OBJECTIVE: Study on the application of WAIS-RC short forms and adult intelligence disability scale in mental impairment assessment. METHODS: Mental impairment assessment cases between July 2009 and March 2011 in judicial appraisal institute of Taizhou University were collected. Assessment results obtained with the WAIS-RC short forms and adult intelligence disability scale were compared with the experts assessing conclusions and analyzed using SPSS 11.5 software. RESULTS: Assessment results with the two scales did not fully comply with the expert's conclusions, with reliability coefficient were 0.785 and 0.940 respectively, correlation coefficient were 0.850 and 0.922 respectively. CONCLUSION: The intelligence assessment was influenced by many factors. When the appraised individuals had nerve dysfunction and mild intelligence disability or mental disorders, the two scales should be used together. When the appraised individuals had moderate intelligence disability or mental disorders, adult intelligence disability scale had advantage.

[Preliminary study on civil capacity rating scale for mental disabled patients].

OBJECTIVE: To create civil capacity rating scale for mentally disabled patients, and explore its feasibility during the forensic psychiatric expertise. METHODS: The civil capacity-related items were determined after discussion and consultation. The civil capacity rating scale for mentally disabled patients was established and the manual was created according to the logistic sequence of the assessment. The rating scale was used during the civil assessment in four institutes. RESULTS: There were 14 items in civil capacity rating scale for mentally disabled patients. Two hundred and two subjects were recruited and divided into three groups according to the experts' opinion on their civil capacities: full civil capacity, partial civil capacity and no civil capacity. The mean score of the three groups were 2.32 +/- 2.45, 11.62 +/- 4.01 and 25.02 +/- 3.90, respectively, and there was statistical differences among the groups. The Cronbach alpha of the rating scale was 0.9724, and during the split-reliability test, the two-splited part of the rating scale were highly correlated (r = 0.9729, P = 0.000). The Spearman correlative coefficient between each item and the score of the rating scale was from 0.643 to 0.882 (P = 0.000). There was good correlation between the conclusion according to the rating scale and the experts' opinion (kappa = 0.841, P = 0.000). When the discriminate analysis was used, 7 items were included into the discrimination equation, and 92.6% subjects were identified as the correct groups using the equation. CONCLUSION: There is satisfied reliability and validity on civil capacity rating scale for mentally disabled patients. The rating scale can be used as effective tools to grade their civil capacity during the forensic expertise.

[Advanced investigation of testamentary capacity of the mentally disordered].

Testamentary capacity is one of the civil competences, it means that a natural person enjoys the capacity or qualification to establish testament and deal with his property. Recently, the cases of testamentary capacity assessment of the mentally disordered are increasing. This article firstly introduces the concepts of the testament as well as the testamentary capacity, and then summarizes the assessment standard of the testamentary capacity, by using the Banks v. Goodfellow case as a basis to make the standard criteria including: the understanding of the nature of a will and codicil, the knowledge of the general extent of one's assets, the knowledge of the natural object of one's bounty, the understanding of the impact of the distribution of the assets of the estate, and the absence of a delusion specifically affecting the distribution of the estate. The impact factors of the testamentary capacity, including dementia, mood disorder, schizophrenia, alcohol, drug, and undue influence, etc., are summarized. Lastly, the related assessment tools such as the Mini-Mental State Examination, the Clock-Drawing Test, and the Testament Definition Scale are introduced briefly.

[Civil competence assessment of the mental disorders involved in contract dispute].

OBJECTIVE: To search the criteria for evaluating the civil competence of the mental disorders involved in contract dispute. METHODS: Data on the interviewee's mental status and the forensic expertise were collected retrospectively. And 6 indexes were selected and graded: awareness of situation, factual understanding of issues, appreciation of likely consequences, rational manipulation of information, functioning in one's own environment and communication of choice. All of the data were analyzed by SPSS. RESULTS: Fifty six cases were included and interviewee's civil competence was graded to three levels: full civil competence, diminished civil competence, and no civil competence. These cases included two types of contract: the real estate related contract (38 cases) and the labor related contract (14 cases). All of the 6 indexes were well correlated to the forensic expertise. The related coefficient was from 0.703 to 0.834, and the interrelated coefficient of the 6 items was also high, from 0.712 to 0.877. CONCLUSION: It is feasible to divide the civil competence of the mental disorders into three grades. As the basis, these 6 indexes mentioned above are representative and can be applied in further standardized and quantified assessment of civil competence.

[Civil competence assessment of the mental disorders involved in compensation of personal injury].

OBJECTIVE: To seek and ascertain indicators that can be used in the civil competence assessment of the mental disorders involved in compensation of personal injury. METHODS: A retrospective study was made on the data related to the interviewee's mental status assessed by forensic experts during the period from 2003 to 2005 in Institute of Forensic Science, Ministry of Justice, P.R.China. The 6 indicators, including awareness of situation, factual understanding of issues, appreciation of likely consequences, rational manipulation of information, functioning in one's own environment, and communication of choice, were graded and statistically analyzed using SPSS 11.5 software. RESULTS: The 6 indicators correlated well with the assessment of forensic experts ,with the related coefficient between 0.632 and 0.876, and the inter-related coefficient among the 6 indicators between 0.575 and 0.911. CONCLUSION: The 6 indicators could be used for the civil competence assessment and may also be taken as the basis for further standardization and quantification of civil competence.