Objective:To investigate the expression and significance ofβ1 integrin, Rac1, and RhoA in invasive micropapillary breast carcinoma (IMPC). Methods:Immunohistochemical staining was performed to detect the expression ofβ1 integrin, Rac1, and RhoA in 89 patients with IMPC and 90 patients with invasive ductal carcinoma-not otherwise specified (IDC-NOS) who were treated between January 2007 and December 2008 in Tianjin Medical University Cancer Institute and Hospital. The relationship among the three proteins and the expression ofβ1 integrin, Rac1, and RhoA with clinicopathological features were determined. Results:β1 integrin (78.7%) and Rac1 (76.4%) were highly expressed in patients with IMPC. This expression was significantly higher than that in patients with IDC-NOS (63.3%and 54.4%). Statistical difference was found between the two groups (P<0.05). Positive rate of RhoA (68.5%) in patients with IMPC was also statistically higher than that in patients with IDC-NOS (44.4%, P=0.001). In patients with IMPC, the expression ofβ1 integrin and Rac1 was positively associated with lymph node metastasis (P<0.05), while the expression ofβ1 integrin was positively correlated with Rac1 expression (P=0.006). Expression of RhoA was positively correlated with lymph node involvement and ER and PR status (P<0.05). However, no correlation was found between RhoA expression and the expression ofβ1 integrin and Rac1 (P>0.05). Conclusion:Thus,β1 integrin, Rac1, and RhoA were overexpressed and might play an important role in the high frequency of metastasis in patients with IMPC. These proteins could be considered as biomarkers for the prognosis and new targets for IMPC therapy.

Breast cancer is one of the major causes of death in women,and its incidence has been increasing year after year.The Rho GTPases,their regulatory proteins and Rho GTPases play an important role in promoting the occurrence and distant metastasis of breast cancer.Here we summarized the current knowledge of the regulation network of Rho GTPases,their regulatory proteins and Rho GTPases on the occurrence and development of breast cancer,and targeted therapy for RHO GTP enzyme pathway in breast cancer.

Depression is a complex mental disease with polygenic inheritance and a high incidence.Our understanding of the clinical manifestations and pathogenesis of depression has recently improved.Continuous progress in gene-editing technologies has increased the construction efficiency and reduced the cost of gene-knockout animals,leading to their increasing use in the fields of basic research and drug development for depression and providing a powerful tool for revealing the pathogenesis of depression.In this review,we summarize recent progress in understanding the roles and mechanisms of candidate genes in depression using knockout model mice.

【Objective】 To investigate whether the blood donors' coagulation status may lead to apheresis platelet aggregation in vitro. 【Methods】 Thirty blood donors with aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times previously and occurred when the last time of apheresis donation were observed in aggregated group (referred to as the experimental group); Thirty donors without aggregation in apheresis platelets collected by AMICUS blood cell separator no less than 3 times were observed in the control group simultaneously. The basic platelet parameters in the two groups, including Plt, MPV, PDW, Pet, P-LCR were detected by automatic blood cell analyzer (BC-3000Plus), and thromboelastogram indexes including reaction time(R), kinetics time(K), kinetics of clot development(α), maximum amplitude (MA) and coagulation index(CI) were tested by Thrombosis elastography (TEG) before collection. With SPSS24.0 software, t test was used to compare the differences between the two groups. 【Results】 The CI value in experimental group was significantly different from that of the control group (0.48± 1.00 vs -0.99 ±1.96, P< 0.05), and there was no significant difference in all above basic platelet parameters and other TEG parameters (P>0.05 ) . 【Conclusion】 The coagulation status of blood donors may be an independent risk factor for the in vitro aggregation of apheresis platelets.

Objective:To construct the second and fourth generations of CAR-T cells targeting fibroblast activation protein (FAP) on the surface of stromal carcinoma-associated fibroblasts and compare their characteristics in vitro and in vivo. Methods:ELISA was used to detect the cytokines secreted by CAR-T cells. Cell proliferation and viability were analyzed by counting. Chemotactic ability was tested by Transwell migration assay. Distribution of T cell subsets was analyzed by flow cytometry. Cytotoxicity was assessed by luciferase bioluminescence. The safety and therapeutic effects were evaluated in a NOG mouse model of metastatic human lung cancer.Results:The expression rates of the second and fourth generations of CAR-T cells (h4BBz CAR-T and h4BBz-7.19 CAR-T) were (74.280±4.384)% and (67.220±4.013)%, respectively. The h4BBz-7.19 CAR-T cells had better in vitro proliferation and chemotactic activity than h4BBz CAR-T cells as they were able to secrete IL-7 and CCL19, while the viability of h4BBz-7.19 CAR-T cells was comparable to that of h4BBz CAR-T cells. There was no significant difference in the expression rate of h4BBz CAR or h4BBz-7.19 CAR between CD4 + T and CD8 + T cells. The proportions of both Naive cells and T memory stem cells (TSCM) in CD4 + and CD8 + T cells were higher in h4BBz-7.19 CAR-T cells than in h4BBz CAR-T cells. Moreover, h4BBz-7.19 CAR-T cells possessed stronger specific cytotoxicity on the target cancer cells than h4BBz CAR-T cells when the ratio of effectors/targets was low ( P1∶1=0.004, P2∶1=0.000 6, P5∶1<0.000 1, P10∶1=0.022, P20∶1=0.116), while the expression of PD-1 on the surface of h4BBz-7.19 CAR-T cells was lower than that on h4BBz CAR-T cells. In the NOG mouse model of metastatic human lung cancer, h4BBz-7.19 CAR-T cells could slow the tumor growth and prolong the survival time of mice without causing weight loss or pathological changes in the organs. Conclusions:The fourth-generation CAR-T cells targeting FAP were shown to have stronger proliferation, better penetration and more potent specific cytotoxicity by secreting IL-7 and CCL19 and could slow the tumor growth and prolong survival by improving tumor immunosuppressive microenvironment. This study provided reference for the clinical application of the fourth generation of CAR-T cells.

【Objective】 To investigate the changes of platelet, white blood cell, red blood cell counts, Hb and PCV before and after plateletpheresis donation. 【Methods】 10 444 platelet donors who donated platelet from Aug 1, 2019 to Jul 31, 2020 were selected as subjects, among which first-time donors were selected as control group and donors who donated twice or more as donation group. After matching gender and age using Propensity Score Matching method in the two groups, the changes of platelet, white blood cell, red blood cell counts, Hb and PCV of platelet blood donors were compared by t test. 【Results】 There were a slight increase in Plt (t=-6.651, P<0.05), a decrease in WBC (t=2.312, P<0.05), a decrease in hemoglobin(t=4.643, P<0.05), and no change in RBC (t=1.439, P>0.05) and in PCV (t=0.030, P>0.05) after plateletpheresis donation. 【Conclusion】 Plateletpheresis donation has an effect on some peripheral blood parameters, but within the normal reference range.

【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

【Objective】 To investigate the prevalence of depression in blood donors and analyze the related factors, so as to develop a rapid depression screening model for blood donors. 【Methods】 A total of 13 015 street whole blood donors in Guangzhou Blood Center during May to August, 2020 filled in an anonymous e-questionnaire, including social demography information and the Patient Health Questionnaire-9 before donation. The cut-off value for detecting depression was 10. Logistic regression by SPSS 26.0 was used to analyze depression related factors. 2-level decision tree with 30/10 as the minimum number of cases in parent/child node, 10-fold cross validation was used to cut items of PHQ-9 to form the depression screening model. 【Results】 364 out of 13 015 (2.80%) street whole blood donors reported a score ≥ 10. Donors with 18-29 years old (P <0.05), unmarried (P<0.05), less than 50 000 RMB household income per year (P< 0.05) were more prone to depression. 81.96% donors in "<10 scores" group, while 3.85%donors in "≥ 10 scores" group were in two terminal nodes formed by Item-6, 2 and 4 of PHQ-9. After verification by the 10 fold crossover method, the estimated misclassification risk of the model was 1.7%. 【Conclusion】 The screening prevalence of depression based on PHQ-9 in Guangzhou blood donors was 2.8%(95% CI: 2.52%-3.09%) . Donation frequency was not related to depression. A rapid and efficient depression screening model for blood donors based on item-6, 2 and 4 of PHQ-9 was developed.