Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.

Trastuzumab is a standard molecular targeted therapy for human epidermal growth factor receptor 2(HER2) -positive breast cancer, which can significantly improve the survival of patients with this molecular subtype of breast cancer. However, the clinical problem of onset or secondary resistance to trastuzumab has limited its efficacy. Therefore, it is very important to explore the mechanism of trastuzumab resistance and formulate countermeasures. Our study described the underlying molecular mechanism of trastuzumab resistance including ERBB2 mutations and nuclear localization, transcriptional and post-translational alterations of ERBB2, over-activation of bypass signaling pathways activation and so on. Then summarize the potential emerging predicting biomarkers and therapeutic strategies for trastuzumab resistance, in order to provide research direction for reversing trastuzumab resistance.

Using questionnaires and task-related EEG signals to reveal hindered reappraisal and biased suppression in individuals with high schizotypal traits.

Although impaired ability to regulate emotion is commonly reported in schizophrenic patients, the exact pattern of regulation of negative emotions in high-risk individuals remains unclear. In the current study, 26 high-schizotypy individuals paired with 26 controls completed an emotion regulation questionnaire (ERQ) and a laboratory emotion regulation task with electroencephalogram (EEG) recording. Two emotion regulation strategies, namely, reappraisal and expression suppression, were concurrently examined. The late positive potential (LPP) and frontal alpha asymmetry (FAA) were selected as two independent neural indicators of the emotion regulation effect. In the ERQ questionnaire, individuals in the high schizotypy group reported higher habitual use of suppression than the controls. During the emotion regulation task, the high  schizotypy group showed no early LPP reduction in reappraisal compared with the control group and exhibited a general negative FAA pattern (left-biased alpha). In conclusion, we found that individuals with high schizotypy exhibited maladaptive regulation of negative emotions, manifested in hindered reappraisal and biased suppression; this may exacerbate the negative affect of such emotions and further serve as a risk factor for psychosis conversion. Early interventions targeting the regulation of negative emotions may be beneficial for individuals with high schizotypal traits.

[Design of ABC damage variable and positioning system for acetabular fractures and 1122 cases multi-center statistic analysis].

OBJECTIVE: To design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures. METHODS: According to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched. RESULTS: Each damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ). CONCLUSION: Compression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.